Expert Commentary

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Because the prevalence of BRCA1 and BRCA2 mutations is elevated among young women diagnosed with breast cancer, guidelines recommend carrier testing for women diagnosed with this disease at age 50 years or younger.¹ Are women being tested, however, and what are their treatment decisions surrounding those test results? The Young Women’s Breast Cancer Study (YWBCS) seeks to answer such questions.

Details of the study
Study investigators recruited women diagnosed with breast cancer at age 40 or younger from 11 academic and community hospitals in the United States and Canada beginning in 2006. There were 897 evaluable participants who were recruited between 2006 and 2014. Their mean age at diagnosis was 35.5 years and 86.1% of them were white non-Hispanic. A respective 84.5% and 99.8% of women had at least a college education and were insured.

Overall, BRCA testing was performed within 1 year of breast cancer diagnosis in 87% of participants, with rates rising from 77% in 2006 to 95% in 2013. Among participants tested, 7.6% had a BRCA1 mutation, 4.5% had a BRCA2 mutation, 4.6% had an indeterminate result of unknown clinical significance, and 81.3% had a negative test result.

A total of 86.4% of women found to be mutation carriers proceeded with risk-reducing bilateral mastectomy; 51.2% found not to be mutation carriers had this same prophylactic surgery.  

What this evidence means for practice
Although it is encouraging to see that the proportion of young women with breast cancer who are receiving counseling and genetic testing is rising, the findings from this study of highly educated, largely white and affluent women is not generalizable to all US women diagnosed with breast cancer at a young age.
     That more than half of BRCA-negative women in this study chose bilateral prophylactic mastectomy, a procedure not recommended in this population, is concerning, and reflects nationwide trends.² The increasing use of next-generation sequencing (which yields information on moderate- and low-penetrance genes in addition to BRCA status) means that women and their providers increasingly are being confronted with genetic testing results that call for formal genetics expertise. Unfortunately, genetics counselors remain in short supply and many clinicians without specific genetics training are offering these tests. As editorialists appropriately point out, these trends may further increase the number of relatively low-risk women proceeding with unwarranted bilateral mastectomy.³ In my practice, I continue to refer women whose family or personal histories indicate high-risk status to a cancer genetics counselor for formal counseling and possible testing.
—Andrew M. Kaunitz, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Because the prevalence of BRCA1 and BRCA2 mutations is elevated among young women diagnosed with breast cancer, guidelines recommend carrier testing for women diagnosed with this disease at age 50 years or younger.¹ Are women being tested, however, and what are their treatment decisions surrounding those test results? The Young Women’s Breast Cancer Study (YWBCS) seeks to answer such questions.

Details of the study
Study investigators recruited women diagnosed with breast cancer at age 40 or younger from 11 academic and community hospitals in the United States and Canada beginning in 2006. There were 897 evaluable participants who were recruited between 2006 and 2014. Their mean age at diagnosis was 35.5 years and 86.1% of them were white non-Hispanic. A respective 84.5% and 99.8% of women had at least a college education and were insured.

Overall, BRCA testing was performed within 1 year of breast cancer diagnosis in 87% of participants, with rates rising from 77% in 2006 to 95% in 2013. Among participants tested, 7.6% had a BRCA1 mutation, 4.5% had a BRCA2 mutation, 4.6% had an indeterminate result of unknown clinical significance, and 81.3% had a negative test result.

A total of 86.4% of women found to be mutation carriers proceeded with risk-reducing bilateral mastectomy; 51.2% found not to be mutation carriers had this same prophylactic surgery.  

What this evidence means for practice
Although it is encouraging to see that the proportion of young women with breast cancer who are receiving counseling and genetic testing is rising, the findings from this study of highly educated, largely white and affluent women is not generalizable to all US women diagnosed with breast cancer at a young age.
     That more than half of BRCA-negative women in this study chose bilateral prophylactic mastectomy, a procedure not recommended in this population, is concerning, and reflects nationwide trends.² The increasing use of next-generation sequencing (which yields information on moderate- and low-penetrance genes in addition to BRCA status) means that women and their providers increasingly are being confronted with genetic testing results that call for formal genetics expertise. Unfortunately, genetics counselors remain in short supply and many clinicians without specific genetics training are offering these tests. As editorialists appropriately point out, these trends may further increase the number of relatively low-risk women proceeding with unwarranted bilateral mastectomy.³ In my practice, I continue to refer women whose family or personal histories indicate high-risk status to a cancer genetics counselor for formal counseling and possible testing.
—Andrew M. Kaunitz, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Because the prevalence of BRCA1 and BRCA2 mutations is elevated among young women diagnosed with breast cancer, guidelines recommend carrier testing for women diagnosed with this disease at age 50 years or younger.¹ Are women being tested, however, and what are their treatment decisions surrounding those test results? The Young Women’s Breast Cancer Study (YWBCS) seeks to answer such questions.

Details of the study
Study investigators recruited women diagnosed with breast cancer at age 40 or younger from 11 academic and community hospitals in the United States and Canada beginning in 2006. There were 897 evaluable participants who were recruited between 2006 and 2014. Their mean age at diagnosis was 35.5 years and 86.1% of them were white non-Hispanic. A respective 84.5% and 99.8% of women had at least a college education and were insured.

Overall, BRCA testing was performed within 1 year of breast cancer diagnosis in 87% of participants, with rates rising from 77% in 2006 to 95% in 2013. Among participants tested, 7.6% had a BRCA1 mutation, 4.5% had a BRCA2 mutation, 4.6% had an indeterminate result of unknown clinical significance, and 81.3% had a negative test result.

A total of 86.4% of women found to be mutation carriers proceeded with risk-reducing bilateral mastectomy; 51.2% found not to be mutation carriers had this same prophylactic surgery.  

What this evidence means for practice
Although it is encouraging to see that the proportion of young women with breast cancer who are receiving counseling and genetic testing is rising, the findings from this study of highly educated, largely white and affluent women is not generalizable to all US women diagnosed with breast cancer at a young age.
     That more than half of BRCA-negative women in this study chose bilateral prophylactic mastectomy, a procedure not recommended in this population, is concerning, and reflects nationwide trends.² The increasing use of next-generation sequencing (which yields information on moderate- and low-penetrance genes in addition to BRCA status) means that women and their providers increasingly are being confronted with genetic testing results that call for formal genetics expertise. Unfortunately, genetics counselors remain in short supply and many clinicians without specific genetics training are offering these tests. As editorialists appropriately point out, these trends may further increase the number of relatively low-risk women proceeding with unwarranted bilateral mastectomy.³ In my practice, I continue to refer women whose family or personal histories indicate high-risk status to a cancer genetics counselor for formal counseling and possible testing.
—Andrew M. Kaunitz, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

To date, screening has not been found effective in reducing mortality from ovarian cancer. Collaborative trial investigators in the United Kingdom studied postmenopausal women in the general population to assess whether early detection by screening could decrease ovarian cancer mortality.

Details of the study
During 2001 to 2005, more than 200,000 UK postmenopausal women aged 50 to 74 years (mean age at baseline, 60.6 years) were randomly assigned to no screening, annual transvaginal ultrasound screening (TVUS), or annual multimodal screening (MMS) with serum CA 125 using the Risk of Ovarian Cancer Algorithm (ROCA), which takes into account changes in CA 125 levels over time. When ROCA scores indicated normal risk for ovarian cancer, women were advised to undergo repeat CA 125 assessment in 1 year. Women with intermediate risk were advised to repeat CA 125 assessment in 3 months, while high-risk women were advised to undergo TVUS.

With a median of 11.1 years of follow-up, ovarian cancer (including fallopian tube malignancies) was diagnosed in 1,282 participants (0.6%), with fatal outcomes among the 3 groups as follows: 0.34% in the no-screening group, 0.30% in the TVUS group, and 0.29% in the MMS group. Based on the results of a planned secondary analysis that excluded prevalent cases of ovarian cancer, annual MMS was associated with an overall average mortality reduction of 20% compared with no screening (P = .021). When the mortality reduction was broken down by years of annual screening, 0 to 7 years was associated with an 8% mortality reduction over no screening, and this jumped to 28% for 7 to 14 annual MMS screening years.

The overall average mortality reduction with TVUS compared with no screening was smaller than with MMS. With MMS, the number needed to screen to prevent 1 death from ovarian cancer was 641.

Assessing unnecessary treatment
False-positive screens that resulted in surgical intervention with findings of benign adnexal pathology or normal adnexa occurred in 14 and 50 per 10,000 screens in the MMS and TVUS groups, respectively. For each ovarian cancer detected in the MMS and TVUS groups, an additional 2 and 10 women, respectively, underwent surgery based on false-positive results.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This massive trial’s findings provide optimism that screening for ovarian cancer can indeed reduce mortality from this uncommon but too-often lethal disease. There are unanswered questions, however, which include the cost-effectiveness of MMS screening and how well this strategy can be implemented outside of a highly centralized and controlled clinical trial. While encouraging, these trial results should be viewed as preliminary until additional efficacy and cost-effectiveness data—and guidance from professional organizations—are available.
—ANDREW M. KAUNITZ, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

To date, screening has not been found effective in reducing mortality from ovarian cancer. Collaborative trial investigators in the United Kingdom studied postmenopausal women in the general population to assess whether early detection by screening could decrease ovarian cancer mortality.

Details of the study
During 2001 to 2005, more than 200,000 UK postmenopausal women aged 50 to 74 years (mean age at baseline, 60.6 years) were randomly assigned to no screening, annual transvaginal ultrasound screening (TVUS), or annual multimodal screening (MMS) with serum CA 125 using the Risk of Ovarian Cancer Algorithm (ROCA), which takes into account changes in CA 125 levels over time. When ROCA scores indicated normal risk for ovarian cancer, women were advised to undergo repeat CA 125 assessment in 1 year. Women with intermediate risk were advised to repeat CA 125 assessment in 3 months, while high-risk women were advised to undergo TVUS.

With a median of 11.1 years of follow-up, ovarian cancer (including fallopian tube malignancies) was diagnosed in 1,282 participants (0.6%), with fatal outcomes among the 3 groups as follows: 0.34% in the no-screening group, 0.30% in the TVUS group, and 0.29% in the MMS group. Based on the results of a planned secondary analysis that excluded prevalent cases of ovarian cancer, annual MMS was associated with an overall average mortality reduction of 20% compared with no screening (P = .021). When the mortality reduction was broken down by years of annual screening, 0 to 7 years was associated with an 8% mortality reduction over no screening, and this jumped to 28% for 7 to 14 annual MMS screening years.

The overall average mortality reduction with TVUS compared with no screening was smaller than with MMS. With MMS, the number needed to screen to prevent 1 death from ovarian cancer was 641.

Assessing unnecessary treatment
False-positive screens that resulted in surgical intervention with findings of benign adnexal pathology or normal adnexa occurred in 14 and 50 per 10,000 screens in the MMS and TVUS groups, respectively. For each ovarian cancer detected in the MMS and TVUS groups, an additional 2 and 10 women, respectively, underwent surgery based on false-positive results.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This massive trial’s findings provide optimism that screening for ovarian cancer can indeed reduce mortality from this uncommon but too-often lethal disease. There are unanswered questions, however, which include the cost-effectiveness of MMS screening and how well this strategy can be implemented outside of a highly centralized and controlled clinical trial. While encouraging, these trial results should be viewed as preliminary until additional efficacy and cost-effectiveness data—and guidance from professional organizations—are available.
—ANDREW M. KAUNITZ, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

To date, screening has not been found effective in reducing mortality from ovarian cancer. Collaborative trial investigators in the United Kingdom studied postmenopausal women in the general population to assess whether early detection by screening could decrease ovarian cancer mortality.

Details of the study
During 2001 to 2005, more than 200,000 UK postmenopausal women aged 50 to 74 years (mean age at baseline, 60.6 years) were randomly assigned to no screening, annual transvaginal ultrasound screening (TVUS), or annual multimodal screening (MMS) with serum CA 125 using the Risk of Ovarian Cancer Algorithm (ROCA), which takes into account changes in CA 125 levels over time. When ROCA scores indicated normal risk for ovarian cancer, women were advised to undergo repeat CA 125 assessment in 1 year. Women with intermediate risk were advised to repeat CA 125 assessment in 3 months, while high-risk women were advised to undergo TVUS.

With a median of 11.1 years of follow-up, ovarian cancer (including fallopian tube malignancies) was diagnosed in 1,282 participants (0.6%), with fatal outcomes among the 3 groups as follows: 0.34% in the no-screening group, 0.30% in the TVUS group, and 0.29% in the MMS group. Based on the results of a planned secondary analysis that excluded prevalent cases of ovarian cancer, annual MMS was associated with an overall average mortality reduction of 20% compared with no screening (P = .021). When the mortality reduction was broken down by years of annual screening, 0 to 7 years was associated with an 8% mortality reduction over no screening, and this jumped to 28% for 7 to 14 annual MMS screening years.

The overall average mortality reduction with TVUS compared with no screening was smaller than with MMS. With MMS, the number needed to screen to prevent 1 death from ovarian cancer was 641.

Assessing unnecessary treatment
False-positive screens that resulted in surgical intervention with findings of benign adnexal pathology or normal adnexa occurred in 14 and 50 per 10,000 screens in the MMS and TVUS groups, respectively. For each ovarian cancer detected in the MMS and TVUS groups, an additional 2 and 10 women, respectively, underwent surgery based on false-positive results.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This massive trial’s findings provide optimism that screening for ovarian cancer can indeed reduce mortality from this uncommon but too-often lethal disease. There are unanswered questions, however, which include the cost-effectiveness of MMS screening and how well this strategy can be implemented outside of a highly centralized and controlled clinical trial. While encouraging, these trial results should be viewed as preliminary until additional efficacy and cost-effectiveness data—and guidance from professional organizations—are available.
—ANDREW M. KAUNITZ, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Early in 2015, SHM published the updated edition of the “Key Principles and Characteristics of an Effective Hospital Medicine Group,” which is a free download via the SHM website. Every hospitalist group should use this comprehensive list of attributes as one important frame of reference to guide ongoing improvement efforts and long-range planning.

In this column and the next two, I’ll split the difference between the very brief list of top success factors for hospitalist groups I wrote about in my March 2011 column and the very comprehensive “Key Characteristics” document. I think these attributes are among the most important to support a high-performing group, yet they are sometimes overlooked or implemented poorly. They are of roughly equal importance and are listed in no particular order.

Deliberately Cultivating a Culture (or Mindset) of Practice Ownership

It’s easy for hospitalists to think of themselves as employees who just work shifts but have no need or opportunity to attend to the bigger picture of the practice or the hospital in which they operate. After all, being a good doctor for your patients is an awfully big job itself, and lots of recruitment ads tell you doctoring is all that will be expected of you. Someone else will handle everything necessary to ensure your practice is successful.

This line of thinking will limit the success of your group.

Your group will perform much better and you’re likely to find your career much more rewarding if you and your hospitalist colleagues think of yourselves as owning your practice and take an active role in managing it. You’ll still need others to manage day-to-day business affairs, but at least a portion of the hospitalists in the group should be actively involved in planning and making decisions about the group’s operations and future evolution.

I encounter hospitalist groups that have become convinced they don’t even have the opportunity to shape or influence their practice. “No one ever listens,” they say. “The hospital executives just do what they want regardless of what we say.” But in nearly every case, that is an exaggeration. Most administrative leaders desperately want hospitalist engagement and thoughtful participation in planning and decision making.

I wrote additional thoughts about the importance of a culture, or mindset, of practice ownership in August 2008. The print version of that column included a short list of questions you could ask yourself to assess whether your own group has such a culture, but it is missing from the web version and can be found at nelsonflores.com/html/quiz.html.

A Formal System of Group ‘Governance’

So many hospitalist groups rely almost entirely on consensus to make decisions. This might work well enough for a very small group (e.g., four or five doctors), but for large groups, it means just one or two dissenters can block a decision and nothing much gets done.

Disagreements about practice operations and future direction are common, so every group should commit to writing some method of how votes will be taken in the absence of consensus. For example, the group might be divided about whether to adopt unit-based assignments or change the hours of an evening (“swing”) shift, and a formal vote might be the only way to make a decision. It’s best if you have decided in advance issues such as what constitutes a quorum, who is eligible to vote, and whether the winning vote requires a simple or super-majority. And a formalized system of voting helps support a culture ownership.

I wrote about this originally in December 2007 and provided sample bylaws your group could modify as needed. Of course, you should keep in mind that if you are indeed employed by a larger entity such as a hospital or staffing company, you don’t have the ability to make all decisions by a vote of the group. Pay raises, staff additions, and similar decisions require support of the employer, and while a vote in support of them might influence what actually happens, it still requires the support of the employer. But there are lots of things, like the work schedule, system of allocating patients across providers, etc., that are usually best made by the group itself, and sometimes they might come down to a vote of the group.

Never Stop Recruiting and Ensure Hospitalists Themselves Are Actively Engaged in Recruiting

I wrote about recruiting originally in July 2008 when there was a shortage of hospitalists everywhere. Since then, the supply of doctors seeking work as a hospitalist has caught up with demand in many major metropolitan areas like Minneapolis and Washington, D.C.

But outside of large markets—that is, in most of the country—demand for hospitalists still far exceeds supply, and groups face ongoing staffing deficits that come with the need for existing doctors to work extra shifts and use locum tenens or other forms of temporary staffing. The potential excess supply of hospitalists in major markets may eventually trickle out and ease the shortages elsewhere, but that hasn’t happened in a big way yet. So for these places, it is crucial to devote a lot of energy and resources to recruiting.

A vital component of successful recruiting is participation in the effort by the hospitalists themselves. I think the best mindset for the hospitalists is to think of themselves as leading recruitment efforts assisted by recruiters rather than the other way around. For example, the lead hospitalist or some other designated doctor should try to respond by phone (if that’s impractical, then respond by email) to every reasonable inquiry from a new candidate within 24 hours and serve as the candidate’s principle point of communication throughout the recruitment process. The recruiter can handle details of things like arranging travel for an interview, but a hospitalist in the group should be the main source of information regarding things like the work schedule, patient volume, compensation, etc. And a hospitalist should serve as the main host during a candidate’s on-site interview.

More to Come …

Next month, I’ll address things like a written policy and procedure manual, clear reporting relationships for the hospitalist group, and roles for advanced practice clinicians (NPs and PAs). TH

Early in 2015, SHM published the updated edition of the “Key Principles and Characteristics of an Effective Hospital Medicine Group,” which is a free download via the SHM website. Every hospitalist group should use this comprehensive list of attributes as one important frame of reference to guide ongoing improvement efforts and long-range planning.

In this column and the next two, I’ll split the difference between the very brief list of top success factors for hospitalist groups I wrote about in my March 2011 column and the very comprehensive “Key Characteristics” document. I think these attributes are among the most important to support a high-performing group, yet they are sometimes overlooked or implemented poorly. They are of roughly equal importance and are listed in no particular order.

Deliberately Cultivating a Culture (or Mindset) of Practice Ownership

It’s easy for hospitalists to think of themselves as employees who just work shifts but have no need or opportunity to attend to the bigger picture of the practice or the hospital in which they operate. After all, being a good doctor for your patients is an awfully big job itself, and lots of recruitment ads tell you doctoring is all that will be expected of you. Someone else will handle everything necessary to ensure your practice is successful.

This line of thinking will limit the success of your group.

Your group will perform much better and you’re likely to find your career much more rewarding if you and your hospitalist colleagues think of yourselves as owning your practice and take an active role in managing it. You’ll still need others to manage day-to-day business affairs, but at least a portion of the hospitalists in the group should be actively involved in planning and making decisions about the group’s operations and future evolution.

I encounter hospitalist groups that have become convinced they don’t even have the opportunity to shape or influence their practice. “No one ever listens,” they say. “The hospital executives just do what they want regardless of what we say.” But in nearly every case, that is an exaggeration. Most administrative leaders desperately want hospitalist engagement and thoughtful participation in planning and decision making.

I wrote additional thoughts about the importance of a culture, or mindset, of practice ownership in August 2008. The print version of that column included a short list of questions you could ask yourself to assess whether your own group has such a culture, but it is missing from the web version and can be found at nelsonflores.com/html/quiz.html.

A Formal System of Group ‘Governance’

So many hospitalist groups rely almost entirely on consensus to make decisions. This might work well enough for a very small group (e.g., four or five doctors), but for large groups, it means just one or two dissenters can block a decision and nothing much gets done.

Disagreements about practice operations and future direction are common, so every group should commit to writing some method of how votes will be taken in the absence of consensus. For example, the group might be divided about whether to adopt unit-based assignments or change the hours of an evening (“swing”) shift, and a formal vote might be the only way to make a decision. It’s best if you have decided in advance issues such as what constitutes a quorum, who is eligible to vote, and whether the winning vote requires a simple or super-majority. And a formalized system of voting helps support a culture ownership.

I wrote about this originally in December 2007 and provided sample bylaws your group could modify as needed. Of course, you should keep in mind that if you are indeed employed by a larger entity such as a hospital or staffing company, you don’t have the ability to make all decisions by a vote of the group. Pay raises, staff additions, and similar decisions require support of the employer, and while a vote in support of them might influence what actually happens, it still requires the support of the employer. But there are lots of things, like the work schedule, system of allocating patients across providers, etc., that are usually best made by the group itself, and sometimes they might come down to a vote of the group.

Never Stop Recruiting and Ensure Hospitalists Themselves Are Actively Engaged in Recruiting

I wrote about recruiting originally in July 2008 when there was a shortage of hospitalists everywhere. Since then, the supply of doctors seeking work as a hospitalist has caught up with demand in many major metropolitan areas like Minneapolis and Washington, D.C.

But outside of large markets—that is, in most of the country—demand for hospitalists still far exceeds supply, and groups face ongoing staffing deficits that come with the need for existing doctors to work extra shifts and use locum tenens or other forms of temporary staffing. The potential excess supply of hospitalists in major markets may eventually trickle out and ease the shortages elsewhere, but that hasn’t happened in a big way yet. So for these places, it is crucial to devote a lot of energy and resources to recruiting.

A vital component of successful recruiting is participation in the effort by the hospitalists themselves. I think the best mindset for the hospitalists is to think of themselves as leading recruitment efforts assisted by recruiters rather than the other way around. For example, the lead hospitalist or some other designated doctor should try to respond by phone (if that’s impractical, then respond by email) to every reasonable inquiry from a new candidate within 24 hours and serve as the candidate’s principle point of communication throughout the recruitment process. The recruiter can handle details of things like arranging travel for an interview, but a hospitalist in the group should be the main source of information regarding things like the work schedule, patient volume, compensation, etc. And a hospitalist should serve as the main host during a candidate’s on-site interview.

More to Come …

Next month, I’ll address things like a written policy and procedure manual, clear reporting relationships for the hospitalist group, and roles for advanced practice clinicians (NPs and PAs). TH

Early in 2015, SHM published the updated edition of the “Key Principles and Characteristics of an Effective Hospital Medicine Group,” which is a free download via the SHM website. Every hospitalist group should use this comprehensive list of attributes as one important frame of reference to guide ongoing improvement efforts and long-range planning.

In this column and the next two, I’ll split the difference between the very brief list of top success factors for hospitalist groups I wrote about in my March 2011 column and the very comprehensive “Key Characteristics” document. I think these attributes are among the most important to support a high-performing group, yet they are sometimes overlooked or implemented poorly. They are of roughly equal importance and are listed in no particular order.

Deliberately Cultivating a Culture (or Mindset) of Practice Ownership

It’s easy for hospitalists to think of themselves as employees who just work shifts but have no need or opportunity to attend to the bigger picture of the practice or the hospital in which they operate. After all, being a good doctor for your patients is an awfully big job itself, and lots of recruitment ads tell you doctoring is all that will be expected of you. Someone else will handle everything necessary to ensure your practice is successful.

This line of thinking will limit the success of your group.

Your group will perform much better and you’re likely to find your career much more rewarding if you and your hospitalist colleagues think of yourselves as owning your practice and take an active role in managing it. You’ll still need others to manage day-to-day business affairs, but at least a portion of the hospitalists in the group should be actively involved in planning and making decisions about the group’s operations and future evolution.

I encounter hospitalist groups that have become convinced they don’t even have the opportunity to shape or influence their practice. “No one ever listens,” they say. “The hospital executives just do what they want regardless of what we say.” But in nearly every case, that is an exaggeration. Most administrative leaders desperately want hospitalist engagement and thoughtful participation in planning and decision making.

I wrote additional thoughts about the importance of a culture, or mindset, of practice ownership in August 2008. The print version of that column included a short list of questions you could ask yourself to assess whether your own group has such a culture, but it is missing from the web version and can be found at nelsonflores.com/html/quiz.html.

A Formal System of Group ‘Governance’

So many hospitalist groups rely almost entirely on consensus to make decisions. This might work well enough for a very small group (e.g., four or five doctors), but for large groups, it means just one or two dissenters can block a decision and nothing much gets done.

Disagreements about practice operations and future direction are common, so every group should commit to writing some method of how votes will be taken in the absence of consensus. For example, the group might be divided about whether to adopt unit-based assignments or change the hours of an evening (“swing”) shift, and a formal vote might be the only way to make a decision. It’s best if you have decided in advance issues such as what constitutes a quorum, who is eligible to vote, and whether the winning vote requires a simple or super-majority. And a formalized system of voting helps support a culture ownership.

I wrote about this originally in December 2007 and provided sample bylaws your group could modify as needed. Of course, you should keep in mind that if you are indeed employed by a larger entity such as a hospital or staffing company, you don’t have the ability to make all decisions by a vote of the group. Pay raises, staff additions, and similar decisions require support of the employer, and while a vote in support of them might influence what actually happens, it still requires the support of the employer. But there are lots of things, like the work schedule, system of allocating patients across providers, etc., that are usually best made by the group itself, and sometimes they might come down to a vote of the group.

Never Stop Recruiting and Ensure Hospitalists Themselves Are Actively Engaged in Recruiting

I wrote about recruiting originally in July 2008 when there was a shortage of hospitalists everywhere. Since then, the supply of doctors seeking work as a hospitalist has caught up with demand in many major metropolitan areas like Minneapolis and Washington, D.C.

But outside of large markets—that is, in most of the country—demand for hospitalists still far exceeds supply, and groups face ongoing staffing deficits that come with the need for existing doctors to work extra shifts and use locum tenens or other forms of temporary staffing. The potential excess supply of hospitalists in major markets may eventually trickle out and ease the shortages elsewhere, but that hasn’t happened in a big way yet. So for these places, it is crucial to devote a lot of energy and resources to recruiting.

A vital component of successful recruiting is participation in the effort by the hospitalists themselves. I think the best mindset for the hospitalists is to think of themselves as leading recruitment efforts assisted by recruiters rather than the other way around. For example, the lead hospitalist or some other designated doctor should try to respond by phone (if that’s impractical, then respond by email) to every reasonable inquiry from a new candidate within 24 hours and serve as the candidate’s principle point of communication throughout the recruitment process. The recruiter can handle details of things like arranging travel for an interview, but a hospitalist in the group should be the main source of information regarding things like the work schedule, patient volume, compensation, etc. And a hospitalist should serve as the main host during a candidate’s on-site interview.

More to Come …

Next month, I’ll address things like a written policy and procedure manual, clear reporting relationships for the hospitalist group, and roles for advanced practice clinicians (NPs and PAs). TH

LAS VEGAS – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

LAS VEGAS – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

LAS VEGAS – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – All four Food and Drug Administration–approved novel oral anticoagulants offer impressive safety advantages over the traditional strategy of low-molecular-weight heparin bridging to warfarin for treatment of acute venous thromboembolism, Dr. Patrick T. O’Gara observed at the Annual Cardiovascular Conference at Snowmass.

He highlighted a European analysis of six phase III clinical trials totaling more than 27,000 patients with venous thromboembolism (VTE) in which dabigatran (Pradaxa), rivaroxaban(Xarelto), apixaban (Eliquis), or edoxaban (Savaysa) was compared to the traditional strategy of unfractionated or low-molecular-weight heparin (LMWH) bridging to warfarin or another vitamin K antagonist. All four NOACs proved statistically noninferior to the traditional strategy in terms of efficacy as defined by prevention of recurrent VTE. Efficacy of NOACs and warfarin was similar regardless of body weight, chronic kidney disease, age, cancer, and pulmonary embolism versus deep venous thrombosis.

In terms of safety, it was no contest: The NOACs were collectively associated with a 39% lower risk of major bleeding, a 64% lower risk of fatal bleeding, and a 63% reduction in intracranial bleeding compared to LMWH/warfarin (Blood 2014 Sep 18;124[12]:1968-75).

“This is a big-ticket winner for the novel oral anticoagulants in the longer-term management of patients who have venous thromboembolic disease – not inferior to a strategy of low-molecular-weight heparin bridging to warfarin and much better with respect to serious consequences of a safety nature,” said Dr. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, Boston.

The pivotal trials for NOACs in VTE were generally structured statistically as noninferiority trials, with one exception: edoxaban has been shown to be superior to warfarin in a prespecified subgroup with submassive pulmonary embolism.

Further strengthening the case for routine use of NOACs in treating acute VTE is the emergence of fast-acting antidotes to the drugs in the event a patient develops a bleeding complication. Idarucizumab (Praxbind) received FDA approval last October as a reversal agent for dabigatran. Many experts think andexanet alpha will likely receive regulatory approval later this year as a universal antidote to all the factor Xa inhibitors, he noted.

It’s estimated that 70% of patients with pulmonary embolism can be classified as low risk and thus eligible for consideration for early hospital discharge and home treatment, provided their social situation is suitable. Pulmonary embolism patients are categorized as low risk if they are hemodynamically stable, don’t require supplemental oxygen, don’t show right ventricular dilatation on CT imaging in the emergency department, and lack serum biomarker evidence of right ventricular strain or injury.

In making decisions about outpatient therapy for VTE, a point worth considering is that two NOACs, rivaroxaban and apixaban, possess the practical advantage of being single-agent therapy. That is, they don’t require a heparin bridge prior to their introduction, as established in the EINSTEIN trial for rivaroxaban and in the AMPLIFY study for apixaban. However, a loading dose is necessary. Rivaroxaban is given at 15 mg b.i.d. for 3 weeks before dropping down to 20 mg once daily. Apixaban has a loading dose of 10 mg b.i.d. for the first 7 days followed by 5 mg b.i.d. thereafter.

“You’ll note that you give a higher loading dose for these particular agents for events that occur on the venous side of the circulation compared with the management of patients who have nonvalvular atrial fibrillation,” Dr. O’Gara said.

In contrast, both dabigatran and edoxaban require either unfractionated or LMWH as bridge before switching to oral therapy.

Dr. O’Gara reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – All four Food and Drug Administration–approved novel oral anticoagulants offer impressive safety advantages over the traditional strategy of low-molecular-weight heparin bridging to warfarin for treatment of acute venous thromboembolism, Dr. Patrick T. O’Gara observed at the Annual Cardiovascular Conference at Snowmass.

He highlighted a European analysis of six phase III clinical trials totaling more than 27,000 patients with venous thromboembolism (VTE) in which dabigatran (Pradaxa), rivaroxaban(Xarelto), apixaban (Eliquis), or edoxaban (Savaysa) was compared to the traditional strategy of unfractionated or low-molecular-weight heparin (LMWH) bridging to warfarin or another vitamin K antagonist. All four NOACs proved statistically noninferior to the traditional strategy in terms of efficacy as defined by prevention of recurrent VTE. Efficacy of NOACs and warfarin was similar regardless of body weight, chronic kidney disease, age, cancer, and pulmonary embolism versus deep venous thrombosis.

In terms of safety, it was no contest: The NOACs were collectively associated with a 39% lower risk of major bleeding, a 64% lower risk of fatal bleeding, and a 63% reduction in intracranial bleeding compared to LMWH/warfarin (Blood 2014 Sep 18;124[12]:1968-75).

“This is a big-ticket winner for the novel oral anticoagulants in the longer-term management of patients who have venous thromboembolic disease – not inferior to a strategy of low-molecular-weight heparin bridging to warfarin and much better with respect to serious consequences of a safety nature,” said Dr. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, Boston.

The pivotal trials for NOACs in VTE were generally structured statistically as noninferiority trials, with one exception: edoxaban has been shown to be superior to warfarin in a prespecified subgroup with submassive pulmonary embolism.

Further strengthening the case for routine use of NOACs in treating acute VTE is the emergence of fast-acting antidotes to the drugs in the event a patient develops a bleeding complication. Idarucizumab (Praxbind) received FDA approval last October as a reversal agent for dabigatran. Many experts think andexanet alpha will likely receive regulatory approval later this year as a universal antidote to all the factor Xa inhibitors, he noted.

It’s estimated that 70% of patients with pulmonary embolism can be classified as low risk and thus eligible for consideration for early hospital discharge and home treatment, provided their social situation is suitable. Pulmonary embolism patients are categorized as low risk if they are hemodynamically stable, don’t require supplemental oxygen, don’t show right ventricular dilatation on CT imaging in the emergency department, and lack serum biomarker evidence of right ventricular strain or injury.

In making decisions about outpatient therapy for VTE, a point worth considering is that two NOACs, rivaroxaban and apixaban, possess the practical advantage of being single-agent therapy. That is, they don’t require a heparin bridge prior to their introduction, as established in the EINSTEIN trial for rivaroxaban and in the AMPLIFY study for apixaban. However, a loading dose is necessary. Rivaroxaban is given at 15 mg b.i.d. for 3 weeks before dropping down to 20 mg once daily. Apixaban has a loading dose of 10 mg b.i.d. for the first 7 days followed by 5 mg b.i.d. thereafter.

“You’ll note that you give a higher loading dose for these particular agents for events that occur on the venous side of the circulation compared with the management of patients who have nonvalvular atrial fibrillation,” Dr. O’Gara said.

In contrast, both dabigatran and edoxaban require either unfractionated or LMWH as bridge before switching to oral therapy.

Dr. O’Gara reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – All four Food and Drug Administration–approved novel oral anticoagulants offer impressive safety advantages over the traditional strategy of low-molecular-weight heparin bridging to warfarin for treatment of acute venous thromboembolism, Dr. Patrick T. O’Gara observed at the Annual Cardiovascular Conference at Snowmass.

He highlighted a European analysis of six phase III clinical trials totaling more than 27,000 patients with venous thromboembolism (VTE) in which dabigatran (Pradaxa), rivaroxaban(Xarelto), apixaban (Eliquis), or edoxaban (Savaysa) was compared to the traditional strategy of unfractionated or low-molecular-weight heparin (LMWH) bridging to warfarin or another vitamin K antagonist. All four NOACs proved statistically noninferior to the traditional strategy in terms of efficacy as defined by prevention of recurrent VTE. Efficacy of NOACs and warfarin was similar regardless of body weight, chronic kidney disease, age, cancer, and pulmonary embolism versus deep venous thrombosis.

In terms of safety, it was no contest: The NOACs were collectively associated with a 39% lower risk of major bleeding, a 64% lower risk of fatal bleeding, and a 63% reduction in intracranial bleeding compared to LMWH/warfarin (Blood 2014 Sep 18;124[12]:1968-75).

“This is a big-ticket winner for the novel oral anticoagulants in the longer-term management of patients who have venous thromboembolic disease – not inferior to a strategy of low-molecular-weight heparin bridging to warfarin and much better with respect to serious consequences of a safety nature,” said Dr. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, Boston.

The pivotal trials for NOACs in VTE were generally structured statistically as noninferiority trials, with one exception: edoxaban has been shown to be superior to warfarin in a prespecified subgroup with submassive pulmonary embolism.

Further strengthening the case for routine use of NOACs in treating acute VTE is the emergence of fast-acting antidotes to the drugs in the event a patient develops a bleeding complication. Idarucizumab (Praxbind) received FDA approval last October as a reversal agent for dabigatran. Many experts think andexanet alpha will likely receive regulatory approval later this year as a universal antidote to all the factor Xa inhibitors, he noted.

It’s estimated that 70% of patients with pulmonary embolism can be classified as low risk and thus eligible for consideration for early hospital discharge and home treatment, provided their social situation is suitable. Pulmonary embolism patients are categorized as low risk if they are hemodynamically stable, don’t require supplemental oxygen, don’t show right ventricular dilatation on CT imaging in the emergency department, and lack serum biomarker evidence of right ventricular strain or injury.

In making decisions about outpatient therapy for VTE, a point worth considering is that two NOACs, rivaroxaban and apixaban, possess the practical advantage of being single-agent therapy. That is, they don’t require a heparin bridge prior to their introduction, as established in the EINSTEIN trial for rivaroxaban and in the AMPLIFY study for apixaban. However, a loading dose is necessary. Rivaroxaban is given at 15 mg b.i.d. for 3 weeks before dropping down to 20 mg once daily. Apixaban has a loading dose of 10 mg b.i.d. for the first 7 days followed by 5 mg b.i.d. thereafter.

“You’ll note that you give a higher loading dose for these particular agents for events that occur on the venous side of the circulation compared with the management of patients who have nonvalvular atrial fibrillation,” Dr. O’Gara said.

In contrast, both dabigatran and edoxaban require either unfractionated or LMWH as bridge before switching to oral therapy.

Dr. O’Gara reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

CHICAGO – Adoption of an organized, systematic approach to ruptured abdominal aortic aneurysm has been inconsistent.

In a recent survey of vascular physicians in the western United States, 60% who accept ruptured abdominal aortic aneurysm (rAAA) transfers do not have a formal protocol for treatment and 70% do not use a transfer protocol or clinical guidelines (J Vasc Surg. 2015 Aug;62:326-30).

Guidelines for the management and transfer of patients with rAAA have been developed in the United Kingdom, but no such guidelines currently exist in the United States.

Patrice Wendling/Frontline Medical News

To address this disparity, the Western Vascular Society used the survey results, existing European guidelines, and a literature review to develop a set of 15 best practice steps for rAAA transfer. The “guidelines” were endorsed by the society members in September 2015 and are to be published early in 2016, Dr. Matthew Mell of Stanford (Calif.) University Medical Center said at a symposium on vascular surgery sponsored by Northwestern University. The guidelines identify four key components to a successful transfer: an organized inter-facility system of care including rapid triage and transport, defined clinical criteria for transfer, standard resuscitation protocols for the transport, and appropriate resources at the receiving hospital.

During transport, aim for a systolic blood pressure of 70 mm Hg to 90 mm Hg, establish peripheral intravenous access, and avoid aggressive fluid resuscitation, the guidelines advise. Blood products may delay the transfer.

Receiving hospitals should provide a simple and reliable method of referral and have formal protocols in place for the treatment of transferred patients.

Centers that receive patients should have endovascular aortic repair capabilities for ruptured aneurysms, including the ability to perform EVAR under local anesthesia, as well as appropriate facilities and expertise, Dr. Mell said. This advice is based mainly on outcomes observed in the IMPROVE trial (Br J Surg. 2014;101;216-24).

Successful programs tend to repair more than 20-25 ruptures per year, have on-site EVAR inventory, and, for the most part, have vascular surgeons able to perform dual open and endovascular repair. Hospital resources in these successful programs have a single phone number for transfer requests, electronic image transfer, immediately available blood products, hospital policy to accept all requests regardless of bed capacity, a contingency plan to create bed capacity after repair, and real-time management between the transfer center, bed control, and clinicians.

“This is really important because a lot of tertiary centers struggle with bed capacity if bottlenecked and a significant number [about one-third] of transfer requests are declined because of lack of capacity or dedicated room,” Dr. Mell said.

In a more recent study, nearly 20% of 4,439 patients who presented with rAAA in New York, California, and Florida were transferred for definitive care. Transfer rates rose yearly during the study period from 14% in 2005 to 22% in 2010 (J Vasc Surg. 2014;60:553-7).

“Transfer is increasingly utilized as a means for definitive care,” Dr. Mell said.

However, one in six of those transferred died without receiving treatment.

In adjusted analyses, inter-facility transfer was associated with significantly lower mortality when only patients receiving treatment were analyzed (adjusted odds ratio, 0.81; P = .02), but was actually associated with higher mortality when patients who died without treatment were also included (aOR, 1.30; P = .01).

“Outcomes after transfer can be improved by better patient selection and more efficient systems of care,” Dr. Mell concluded. “Guidelines may help; it’s too soon to know, but successful transfer programs require forethought, resources, and alignment of all stakeholders.”

Dr. Mell reported having no conflicts of interest.

CHICAGO – Adoption of an organized, systematic approach to ruptured abdominal aortic aneurysm has been inconsistent.

In a recent survey of vascular physicians in the western United States, 60% who accept ruptured abdominal aortic aneurysm (rAAA) transfers do not have a formal protocol for treatment and 70% do not use a transfer protocol or clinical guidelines (J Vasc Surg. 2015 Aug;62:326-30).

Guidelines for the management and transfer of patients with rAAA have been developed in the United Kingdom, but no such guidelines currently exist in the United States.

Patrice Wendling/Frontline Medical News

To address this disparity, the Western Vascular Society used the survey results, existing European guidelines, and a literature review to develop a set of 15 best practice steps for rAAA transfer. The “guidelines” were endorsed by the society members in September 2015 and are to be published early in 2016, Dr. Matthew Mell of Stanford (Calif.) University Medical Center said at a symposium on vascular surgery sponsored by Northwestern University. The guidelines identify four key components to a successful transfer: an organized inter-facility system of care including rapid triage and transport, defined clinical criteria for transfer, standard resuscitation protocols for the transport, and appropriate resources at the receiving hospital.

During transport, aim for a systolic blood pressure of 70 mm Hg to 90 mm Hg, establish peripheral intravenous access, and avoid aggressive fluid resuscitation, the guidelines advise. Blood products may delay the transfer.

Receiving hospitals should provide a simple and reliable method of referral and have formal protocols in place for the treatment of transferred patients.

Centers that receive patients should have endovascular aortic repair capabilities for ruptured aneurysms, including the ability to perform EVAR under local anesthesia, as well as appropriate facilities and expertise, Dr. Mell said. This advice is based mainly on outcomes observed in the IMPROVE trial (Br J Surg. 2014;101;216-24).

Successful programs tend to repair more than 20-25 ruptures per year, have on-site EVAR inventory, and, for the most part, have vascular surgeons able to perform dual open and endovascular repair. Hospital resources in these successful programs have a single phone number for transfer requests, electronic image transfer, immediately available blood products, hospital policy to accept all requests regardless of bed capacity, a contingency plan to create bed capacity after repair, and real-time management between the transfer center, bed control, and clinicians.

“This is really important because a lot of tertiary centers struggle with bed capacity if bottlenecked and a significant number [about one-third] of transfer requests are declined because of lack of capacity or dedicated room,” Dr. Mell said.

In a more recent study, nearly 20% of 4,439 patients who presented with rAAA in New York, California, and Florida were transferred for definitive care. Transfer rates rose yearly during the study period from 14% in 2005 to 22% in 2010 (J Vasc Surg. 2014;60:553-7).

“Transfer is increasingly utilized as a means for definitive care,” Dr. Mell said.

However, one in six of those transferred died without receiving treatment.

In adjusted analyses, inter-facility transfer was associated with significantly lower mortality when only patients receiving treatment were analyzed (adjusted odds ratio, 0.81; P = .02), but was actually associated with higher mortality when patients who died without treatment were also included (aOR, 1.30; P = .01).

“Outcomes after transfer can be improved by better patient selection and more efficient systems of care,” Dr. Mell concluded. “Guidelines may help; it’s too soon to know, but successful transfer programs require forethought, resources, and alignment of all stakeholders.”

Dr. Mell reported having no conflicts of interest.

CHICAGO – Adoption of an organized, systematic approach to ruptured abdominal aortic aneurysm has been inconsistent.

In a recent survey of vascular physicians in the western United States, 60% who accept ruptured abdominal aortic aneurysm (rAAA) transfers do not have a formal protocol for treatment and 70% do not use a transfer protocol or clinical guidelines (J Vasc Surg. 2015 Aug;62:326-30).

Guidelines for the management and transfer of patients with rAAA have been developed in the United Kingdom, but no such guidelines currently exist in the United States.

Patrice Wendling/Frontline Medical News

To address this disparity, the Western Vascular Society used the survey results, existing European guidelines, and a literature review to develop a set of 15 best practice steps for rAAA transfer. The “guidelines” were endorsed by the society members in September 2015 and are to be published early in 2016, Dr. Matthew Mell of Stanford (Calif.) University Medical Center said at a symposium on vascular surgery sponsored by Northwestern University. The guidelines identify four key components to a successful transfer: an organized inter-facility system of care including rapid triage and transport, defined clinical criteria for transfer, standard resuscitation protocols for the transport, and appropriate resources at the receiving hospital.

During transport, aim for a systolic blood pressure of 70 mm Hg to 90 mm Hg, establish peripheral intravenous access, and avoid aggressive fluid resuscitation, the guidelines advise. Blood products may delay the transfer.

Receiving hospitals should provide a simple and reliable method of referral and have formal protocols in place for the treatment of transferred patients.

Centers that receive patients should have endovascular aortic repair capabilities for ruptured aneurysms, including the ability to perform EVAR under local anesthesia, as well as appropriate facilities and expertise, Dr. Mell said. This advice is based mainly on outcomes observed in the IMPROVE trial (Br J Surg. 2014;101;216-24).

Successful programs tend to repair more than 20-25 ruptures per year, have on-site EVAR inventory, and, for the most part, have vascular surgeons able to perform dual open and endovascular repair. Hospital resources in these successful programs have a single phone number for transfer requests, electronic image transfer, immediately available blood products, hospital policy to accept all requests regardless of bed capacity, a contingency plan to create bed capacity after repair, and real-time management between the transfer center, bed control, and clinicians.

“This is really important because a lot of tertiary centers struggle with bed capacity if bottlenecked and a significant number [about one-third] of transfer requests are declined because of lack of capacity or dedicated room,” Dr. Mell said.

In a more recent study, nearly 20% of 4,439 patients who presented with rAAA in New York, California, and Florida were transferred for definitive care. Transfer rates rose yearly during the study period from 14% in 2005 to 22% in 2010 (J Vasc Surg. 2014;60:553-7).

“Transfer is increasingly utilized as a means for definitive care,” Dr. Mell said.

However, one in six of those transferred died without receiving treatment.

In adjusted analyses, inter-facility transfer was associated with significantly lower mortality when only patients receiving treatment were analyzed (adjusted odds ratio, 0.81; P = .02), but was actually associated with higher mortality when patients who died without treatment were also included (aOR, 1.30; P = .01).

“Outcomes after transfer can be improved by better patient selection and more efficient systems of care,” Dr. Mell concluded. “Guidelines may help; it’s too soon to know, but successful transfer programs require forethought, resources, and alignment of all stakeholders.”

Dr. Mell reported having no conflicts of interest.

Heart failure management has become increasingly complex over the past couple of decades, with new drugs and drug combinations, new uses for potentially life-saving implanted devices, and a more sophisticated appreciation of the ways that various comorbidities complicate a heart failure patient’s clinical status. These expanded dimensions of heart failure care resulted in the establishment in 2008 of a new secondary subspecialty, Advanced Heart Failure and Transplant Cardiology, aimed at training and certifying physicians in all the nuances of complex heart failure diagnostics and care.

But as the 2009 manifesto announcing this new heart failure subspecialty detailed, care for the vast majority of U.S. patients with heart failure remains in the hands of internal medicine primary care physicians (PCPs) and general cardiologists (J Am Coll Cardiol. 2009 Mar 10;53[10]:834-6). To some extent this is a manpower issue. The estimated number of Americans living with heart failure exceeds 5 million, a figure that dwarfs the very modest number of U.S. physicians and clinicians who are certified or self-identified heart failure specialists.

As of today, fewer than 1,000 U.S. physicians have received formal certification as heart failure subspecialists through the examination administered in 2010, 2012, and 2014, said Michele Blair, chief executive officer of the Heart Failure Society of America. A more liberal definition of a heart failure specialist might include the roughly 3,000 unique physicians (mostly cardiologists, but also some hospitalists and emergency physicians) who have recently attended an annual meeting of the HFSA, as well as the roughly 2,300 physician assistants and nurse practitioners who have shown a heart failure interest by coming to a recent HFSA meeting. But even these expanded estimates calculate out to about 1 clinician with a special interest in heart failure for each 1,000 heart failure patients, not a very reassuring ratio.

The burgeoning numbers of heart failure patients, compared with the relative scarcity of both heart failure experts and general cardiologists, raises issues of how primary-care internists best share this management responsibility. Recent interviews with several heart failure subspecialists and primary care internists provide some insight into how this division of labor is now playing out in routine U.S. practice. What often occurs is that primary care internists take exclusive responsibility for caring for heart failure patients until they feel they are getting in over their heads, at which time they’ll consult with a cardiology colleague or refer the patient to a cardiologist. That moment of recognition by the generalist – that the demands and complexity of the case exceed their comfort level – varies widely, with some PCPs referring patients as soon as heart failure symptoms appear while others stay comfortable as the primary care giver even as a patient’s disease deteriorates to a more advanced stage.

Heart failure specialists highlighted their reliance on PCPs to take an ongoing, active role even for patients with significantly advanced heart failure, as generalists are well suited to coordinating the multispecialty care that such patients usually require, with attention to their need for lifestyle modifications as well as management of their diabetes, sleep apnea, chronic obstructive pulmonary disease, renal failure, and other comorbidities.

Mitchel L. Zoler/Frontline Medical News

As Dr. Michael K. Ong, a primary care internist at the University of California, Los Angeles, said in an interview, his heart failure specialist colleague manages patients’ heart failure; “I manage [or refer] everything else not directly related to the heart failure.”

The most successful U.S. care models seem to be some variation on a team-care approach, in which physicians collaborate with pharmacists, nurses, rehabilitation specialists, and social workers as well as specialists, a team that would include and perhaps be led by either a primary care internist, a cardiologist, or a heart failure specialist but would also broadly include physicians able to deal with all the morbidity facets of heart failure. It’s a model that remains unavailable in many U.S. settings or is just starting to emerge, as fee-for-service coverage of patients gets replaced by population-management models that better accommodate the upfront financial demands of coordinated team care. It makes financial sense a few years down the road when improved patient outcomes result in cost savings.

Primary care and patients with symptomatic heart failure

The heart failure definitions and staging system established in 2001 by a guidelines panel of the American College of Cardiology and American Heart Association defined stage A heart failure as starting before a patient exhibits any heart failure symptoms (the classic ones include dyspnea, rales, and peripheral edema). The panel designated symptomatic heart failure patients as stage C. Patients without heart failure symptoms but with one or more risk factors (such as hypertension, diabetes, obesity, and cardiovascular disease) plus structural heart disease (such as cardiomyopathy or other forms of heart remodeling) were designated stage B. The panel said that people at stage A had one or more risk factors but no structural heart changes and no heart failure symptoms.

Although stage-A heart failure patients are clearly the types of people most often seen and cared for by PCPs, many of these physicians, as well as many heart failure specialists, don’t consider patients who have only hypertension or only diabetes or only obesity as yet having heart failure. That paradox deserves more discussion, but the best way to begin talking about PCPs and heart failure patients is when patients are symptomatic and have what everyone would agree is heart failure.

Even though the ACC/AHA staging system places stage C patients well down the heart failure road, stage C is usually when patients are first diagnosed with heart failure. Although the diagnosis is often first made by a hospitalist or emergency-department physician when severe and sudden-onset heart failure symptoms drive the patient to a hospital, or the diagnosis originates with a cardiologist or heart failure specialist when the patient’s presentation and differential diagnosis isn’t straightforward, most commonly the diagnosis starts with a PCP in an office encounter with a patient who is symptomatic but not acutely ill.

“Patients with shortness of breath or other forms of effort intolerance most often seek care from PCPs. The differential diagnosis of dyspnea is long and complex. Recognition that a patient with dyspnea may have HF is crucial” for timely management and treatment, said Dr. Mary Norine Walsh, medical director of Heart Failure and Cardiac Transplantation at St. Vincent Heart Center in Indianapolis.

At the Mayo Clinic in Rochester, Minn., “most of the heart failure diagnoses are done by PCPs, usually first identified at stage C when a patient comes in with symptoms. Stage B heart failure is usually only identified as an incidental finding when echocardiography is done for some other reason,” said Dr. Paul M. McKie, a heart failure cardiologist who works closely with the primary-care staff at Mayo as an embedded consultant cardiologist.

Mitchel L. Zoler/Frontline Medical News

According to Dr. Mariell L. Jessup, a heart failure physician and professor at the University of Pennsylvania in Philadelphia, a key to PCPs promptly identifying patients with recent-onset, stage C heart failure is to keep the disease as well as its prominent risk factors at the top of their differential-diagnosis list for at-risk patients. “Heart failure is a common disorder,” Dr. Jessup said, and must be considered for patients with shortness of breath. “The leading causes of heart failure are hypertension, obesity, and diabetes. So keep heart failure in mind, especially for patients with one or more of these risk factors.”

Although PCPs might order an echocardiography examination or a lab test like measurement of brain natriuretic protein (BNP) to help nail down the diagnosis, they often leave reading the echocardiography results to a cardiologist colleague. “When a PCP orders an echo it’s automatically read by a cardiologist, and then we get the cardiologist’s report. I don’t read echos myself,” said Dr. Rebecca J. Cunningham, an internal medicine PCP at Brigham and Women’s Hospital in Boston who frequently sees patients with heart failure as medical director of the hospital’s Integrated Care Management Program. “I had one PCP colleague who undertook additional training to learn to read echos himself, but that’s unusual.”

Dr. Mary Ann Bauman, an internal medicine PCP and medical director for Women’s Health and Community Relations at INTEGRIS Health in Oklahoma City, noted a similar division of labor. “If a patient has shortness of breath, maybe some edema, and I hear a few rales, but is totally functional, I always order an echo but I don’t read it. I refer the echo to a cardiologist who then sends me a report,” Dr. Bauman said in an interview. “If I think the patient may have heart failure I’ll also order a BNP or NT-proBNP test. If I suspect heart failure and the BNP is high, it’s a red flag. BNP is another tool for getting the diagnosis right.”

The next step seems much more variable. Some PCPs retain primary control of heart failure management for many of their patients, especially when stage C patients remain stable and functional on simple, straightforward treatment and particularly when they have heart failure with preserved ejection fraction (HFpEF), usually defined as a left ventricular ejection fraction that is at least 40%-45%. Consultation or referral to a cardiologist or heart-failure physician seems much more common for patients with frequent decompensations and hospitalizations or patients with heart failure with reduced ejection fraction (HFrEF). But the main thread reported by both PCPs and cardiologists is that it all depends and varies for each patient and for each PCP depending on what patient responsibilities a PCP feels comfortable taking on.

Dr. Bauman sits at one end of the spectrum: “If it looks like a patient has heart failure, I refer them right away; I don’t wait for decompensation to occur. I want to be sure that there are no nuances in the patient that need something before I recognize it. Most of my PCP partners do the same. You don’t know what it is you don’t know. For me, it’s better to refer the patient right away so the patient has a cardiologist who already knows them who can be called if they start to decompensate.”

Dr. Bauman cited the increasing complexity of heart failure management as the main driver of her current approach, which she contrasted to how she dealt with heart failure patients 20 years ago. “It’s become so complicated that, as a PCP, I don’t feel that I can keep up” with the optimal ways to manage every heart failure patient. “I might not give my heart failure patients the best care they could receive.” The aspects of care that Dr. Bauman said she can provide to heart failure patients she has referred include “dealing with lifestyle changes, making sure patients are taking their medications and getting to their appointments, adjusting their heart-failure medication dosages as needed once they start on the drugs, and seeing that their diabetes and hypertension are well controlled. That is the role of the PCP. But when it comes to deciding which HF medications to use, that’s when I like to have a cardiologist involved.”

But the PCPs at Mayo Clinic often take a different tack, said Dr. McKie. “If the patient is a simple case of heart failure with no red flags and the patient is doing relatively well on treatment with simple diuretic treatment, then initiation of heart failure medications and ongoing management is often directed by the PCP with some cardiology backup as needed,” he said. But Dr. McKie conceded that a spectrum of PCP approaches exists at Mayo as well. “A lot depends on the patient and on the specific provider. Some patients we never get calls about; their PCPs are excellent at managing diuretics and uptitrating beta-blockers and ACE inhibitors. We may only get called if the patient decompensates, But other PCPs are very uncomfortable and they request that we get involved as soon as the diagnosis of stage C heart failure is made. So there is a wide range.” Dr. McKie noted that he thinks it is appropriate for himself or one of his cardiology colleagues to get more active when the HFrEF patient’s ejection fraction drops below 40% and certainly below 35%. That’s because at this stage, patients also need treatment with an aldosterone receptor antagonist such as spironolactone, and they undergo consideration for receiving an implantable cardioverter defibrillator or a cardiac resynchronization therapy device.

Mitchel L. Zoler/Frontline Medical News

“There is nothing magic about heart failure management; it is very well proscribed by guidelines. Nothing precludes a PCP from taking ownership” of heart failure patients, said Dr. Akshay S. Desai, a heart failure cardiologist at Brigham and Women’s Hospital. “I think there is some fear among PCPs that they intrude” by managing heart failure patients. But for patients with structural heart disease or even left ventricular dysfunction, “PCPs should feel empowered to start standard heart failure treatments, including ACE inhibitors and beta-blockers, especially because half of heart failure patients have HFpEF, and PCPs often don’t refer HFpEF patients to cardiologists. It’s the patients with left ventricular dysfunction who end up in heart failure clinics,” Dr. Desai said.

On the other hand, Dr. Desai cautioned PCPs against waiting too long to bring more complex, sicker, and harder-to-manage patients to the attention of a heart failure specialist.

“What we worry about are late referrals, when patients are profoundly decompensated,” he said. “By the time they show up [at a heart failure clinic or emergency department] they have end-organ dysfunction,” which makes them much harder to treat and maybe irreversible. “Recognizing heart failure early is the key, and early referral is an obligation” when a heart failure patient is deteriorating or becomes too complex for a PCP to properly manage, Dr. Desai advised.

But even when heart failure patients develop more severe disease, with significantly depressed left ventricular function or frequent decompensations, PCPs continue to play a valuable role in coordinating the wide range of treatments patients need for their various comorbidities.

“Once a cardiologist or heart failure physician is involved there is still a role for PCPs” said Dr. Monica R. Shah, deputy chief of the Heart Failure and Arrhythmia Branch of the National Heart, Lung, and Blood Institute in Bethesda, Md. “Heart failure patients are complex, it’s not just one organ system that’s affected, and you need a partnership between cardiologists and PCPs to coordinate all of a patient’s care. A heart failure physician needs to work with a PCP to be sure that the patient’s health is optimal. Collaboration between cardiologists and PCPs is key to ensure that optimal care is effectively delivered to patients,” Dr. Shah said in an interview.

“Keeping the PCP at the center of the care team is critical, especially with the multiple comorbidities that HF patients can have, including chronic obstructive pulmonary disease, diabetes, renal failure, sleep apnea, atrial fibrillation, and degenerative joint disease. Before you know it you have a half-dozen subspecialists involved in care and it can become uncoordinated. Keeping the PCP at the center of the team and providing the PCP with support from specialists as needed is critical,” said Dr. McKie.

Even for the most severe heart failure patients, PCPs can still play an important role by providing palliative care and dealing with end-of-life issues, specialists said.

Primary care and heart failure’s antecedents

The other, obvious time in heart failure’s severity spectrum for PCPs to take a very active role is with presymptomatic, stage A patients. Perhaps the only controversial element of this is whether such patients really have a form of heart failure and whether is it important to conceptualize heart failure this way.

The notion of stage A heart failure dates back to the 2001 edition of heart failure diagnosis and management recommendations issued by a panel organized by the ACC and AHA (J Am Coll Cardiol. 2001 Dec;38[7]:2101-13). The 2001 writing committee members said that they “decided to take a new approach to the classification of heart failure that emphasized both the evolution and progression of the disease.” They defined stage A patients as presymptomatic and without structural heart disease but with “conditions strongly associated with the development of heart failure,” specifically systemic hypertension, coronary artery disease, diabetes, a history of cardiotoxic drug therapy or alcohol abuse, a history of rheumatic fever, or a family history of cardiomyopathy.

When the ACC and AHA panel members next updated the heart failure recommendations in 2005, they seemed to take a rhetorical step back, saying that stage A and B “are clearly not heart failure but are an attempt to help healthcare providers identify patients early who are at risk for developing heart failure. Stage A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF.” (J Am Coll Cardiol. 2005 Sept. 46[6]:1116-43) In 2005, the panel also streamlined the list of risk factors that identify stage A heart failure patients: hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, patients who have taken cardiotoxins, or patients with a family history of cardiomyopathy. The 2009 recommendation update left this definition of stage A heart failure unchanged, but in 2013 the most recent update devoted less attention to explaining the significance of the stage-A heart failure, although it clearly highlighted the importance of controlling hypertension, diabetes, and obesity as ways to prevent patients from developing symptomatic heart failure (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-e239).

The subtle, official tweaking of the stage A (and B) heart failure concept during 2001-2013, as well establishment of stage A in the first place, seems to have left both PCPs and heart failure specialists unsure on exactly how to think about presymptomatic people with one or more of the prominent heart failure risk factors of hypertension, diabetes, and obesity. While they uniformly agree that identifying these risk factors and then treating them according to contemporary guidelines is hugely important for stopping or deferring the onset of heart failure, and they also agree that this aspect of patient care is clearly a core responsibility for PCPs, many also say that they don’t think of presymptomatic patients as having heart failure of any type despite the stage A designation on the books.

One exception is St. Vincent’s Dr. Walsh. “I think the writers of the 2001 heart failure guidelines had an inspired approach. Identifying patients with hypertension, diabetes, coronary artery disease, etc., as patients with heart failure has helped drive home the point that treatment and control of these diseases is crucial,” she said in an interview. “But I am not sure all physicians have adopted the concept. “Uncontrolled hypertension is prevalent, and not viewed by all as resulting in heart failure down the road. Diabetes and hypertension are very important risk factors for the development of heart failure in women,” she added. “I’m especially diligent in ensuring that women with one or both of these diseases get treated aggressively.”

Highlighting specifically the fundamental role that uncontrolled hypertension plays in causing heart failure, the University of Pennsylvania’s Dr. Jessup estimated that controlling hypertension throughout the U.S. population could probably cut heart failure incidence in half.

Others draw a sharper contrast between the risk factor stage and the symptomatic stages of heart failure, though they all agree on the importance of risk factor management by PCPs. “Hypertension does not mean that a patient has heart failure; it means they have a risk factor for heart failure and the patient is in the prevention stage,” said the NHLBI’s Dr. Shah. ”The most important role for PCPs is to identify the risk factors and prevent development of [symptomatic] heart failure. This is where PCPs are critically important because patients present to them at the early stages.”

Dr. Bauman, the PCP with INTEGRIS in Oklahoma City, generally doesn’t conflate risk factors with stage A heart failure. “I look at every patient with hypertension or diabetes as a person at risk for cardiovascular disease. I push them to get their blood pressure and glycemia under control. But I don’t think of them as stage A heart failure patients. I think of them as patients at risk for heart failure, but also at risk for atrial fibrillation, MI, and stroke. I think about their risk, but I don’t label them in my mind as having stage A heart failure. I think that this is a patient at risk for cardiovascular disease and that I must do what I should to manage their risk factors.”

“I don’t personally think about patients having stage A heart failure,” agreed Dr. Cunningham, a PCP at Brigham and Women’s Hospital. “When I see patients with hypertension, I counsel them about what matters to them so that they will take their medications, because if they currently feel fine they may not understand the long-term risk they face. So I invest time in making the patient understand why their hypertension is important and the risks it poses, so that in the long-run they won’t have a stroke or MI or develop heart failure. But I don’t think that the stage A definition has changed my approach; I already think of hypertension as a precursor to a variety of bad downstream consequences. I don’t think of someone as a heart failure patient just because they have hypertension, and I don’t think that every patient with hypertension will develop heart failure.” Speaking of her colleagues, Dr. Cunningham added, “I don’t have a sense that the stages of heart failure have made much of an impact on how other PCPs talk with patients or plan their care.”

“The heart failure staging system is useful from the standpoint of emphasizing that the disease begins with primordial risk and progresses through a period of structural injury during which patients may not be symptomatic,” summed up Dr. Desai. “But practically, most of us confront the diagnosis of heart failure when patients become symptomatic and reach stage C.”

Can an intensified approach better slow stage A progression?

One of the inherent limitations right now in referring to patients as having stage A heart failure is that it adds little to how heart failure risk factors are managed. A patient with hypertension undergoing appropriate care will receive treatment to lower blood pressure to recommended goal levels. The antihypertensive treatment remains the same regardless of whether the patient is considered to have only hypertension or whether the treating physician also thinks of the patient as having stage A heart failure. The same applies to patients diagnosed with diabetes; their hyperglycemia-controlling treatment remains unchanged whether or not their physician labels them as stage A heart failure patients.

But what if an evidence-based way existed to not only identify patients with hypertension or diabetes, but to identify within those patients the subset who faced a particularly increased risk for developing heart failure? And what if an evidence-based intervention existed that could be added to standard blood pressure–lowering or hyperglycemia-controlling interventions and had proved to slow or stop progression of patients to heart failure?

Preliminary evidence that screening for stage A heart failure patients can successfully identify a subset at elevated risk for developing symptomatic heart failure and that intensified risk-factor control helped mitigate this risk appeared in two reports published in 2013. But both studies were relatively small, they ran in Europe, and neither has undergone replication in a U.S. study in the 2.5 years since their publication.

The larger study, STOP-HF (St. Vincent’s Screening to Prevent Heart Failure), included patients at 39 primary care practices in Ireland, a study organized by researchers at St. Vincent’s University Hospital in Dublin. They enrolled people without symptoms of heart failure who were at least 41 years old and had at least one of these risk factors: hypertension, hypercholesterolemia, obesity, vascular disease, diabetes, an arrhythmia, or valvular disease: In short, primarily stage A heart failure patients.

The researchers then tested 1,374 of these people for their baseline blood level of BNP and randomized them into two intervention arms. For those randomized to the active arm, the PCPs for these people received an unblinded report of the BNP results, and those with a level of 50 pg/mL or higher underwent further assessment by screening echocardiography and intensified risk-factor control, including risk-factor coaching by a nurse. Those randomized to this arm who had a lower BNP level at baseline underwent annual follow-up BNP screening, and if their level reached the 50 pg/ML threshold they switched to the more intensified protocol. Those randomized to the control arm received a more standard program of risk-factor modification and their BNP levels were never unblinded.

After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).

The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).

Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.

“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.

“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.

She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.

“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”

The economic barrier to intensified stage-A management

Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.

“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.

“This speaks to the need for more population-based preventive management, which PCPs are trying to start to do, but currently we are nowhere near fulfilling that potential,” said Dr. Cunningham. The barrier is having clinical resources for help in managing lower-risk patients, to make sure they receive all the interventions they should. We’re now trying to start using care teams for patients with diabetes or other conditions. The biggest gap is that we don’t have the resources; we don’t have enough nurses on our staff to intervene” for all the patients who could potentially benefit. “Right now, we can only afford to use nurses for selected, high-risk patients.” The challenge is to have a care model that allows a lot of upfront costs to generate savings over a long-term time horizon, he said. “It’s very important for improving population health, but it’s hard to make it happen in our current health care system.”

Dr. Ahmad noted the enormous downside of a health system that is not proactive and often waits for heart failure patients to declare themselves with severe illness.

“The majority of heart failure patients I see drifted through the health care system” without recognition of their accumulating morbidity. “By the time they show heart failure symptoms, their disease is pretty advanced and we have real difficulty managing it. A lot of patients do not have their heart failure managed until they fall off the edge and their condition is much less modifiable. If we could identify these patients sooner, it would help both them and the health care system. It would be great to have objective measures that could help PCPs identify early abnormal patients who need more aggressive management. In much of U.S. practice, heart failure management is more specialty driven. It might be different in closed systems, but in many heart failure practices there is no PCP coordination. The health care system is not set up to allow PCPs to take care of these issues.”

Dr. Bauman said she sees some reason for optimism in looming reimbursement changes, where population management might help drive a shift toward more team care for heart failure and a focus on earlier identification of patients at risk and intervention at early stages of their disease.

“As we move toward population management it becomes more obvious that you need a team approach to managing heart failure, involving not just physicians but also pharmacists, nurses, social workers, and care coordinators. In my system, INTEGRIS, the whole-team management approach is beginning to happen. It’s new to primary care to apply a large team of clinicians; it takes a lot of resources. Being able to afford a team was a problem when we were paid by fee-for-service, it wasn’t practical. Population management will make it possible.”

Dr. Desai has been a consultant to Novartis, Merck, St. Jude, and Relypsa and has received research funding from Novartis and AtCor Medical. Dr. Redfield has been a consultant to Merck and Eli Lilly. Dr. Ahmad has been a consultant to Roche. Dr. Ong, Dr. Walsh, Dr. Jessup, Dr. McKie, Dr. Bauman, Dr. Shah, and Dr. Cunningham had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure management has become increasingly complex over the past couple of decades, with new drugs and drug combinations, new uses for potentially life-saving implanted devices, and a more sophisticated appreciation of the ways that various comorbidities complicate a heart failure patient’s clinical status. These expanded dimensions of heart failure care resulted in the establishment in 2008 of a new secondary subspecialty, Advanced Heart Failure and Transplant Cardiology, aimed at training and certifying physicians in all the nuances of complex heart failure diagnostics and care.

But as the 2009 manifesto announcing this new heart failure subspecialty detailed, care for the vast majority of U.S. patients with heart failure remains in the hands of internal medicine primary care physicians (PCPs) and general cardiologists (J Am Coll Cardiol. 2009 Mar 10;53[10]:834-6). To some extent this is a manpower issue. The estimated number of Americans living with heart failure exceeds 5 million, a figure that dwarfs the very modest number of U.S. physicians and clinicians who are certified or self-identified heart failure specialists.

As of today, fewer than 1,000 U.S. physicians have received formal certification as heart failure subspecialists through the examination administered in 2010, 2012, and 2014, said Michele Blair, chief executive officer of the Heart Failure Society of America. A more liberal definition of a heart failure specialist might include the roughly 3,000 unique physicians (mostly cardiologists, but also some hospitalists and emergency physicians) who have recently attended an annual meeting of the HFSA, as well as the roughly 2,300 physician assistants and nurse practitioners who have shown a heart failure interest by coming to a recent HFSA meeting. But even these expanded estimates calculate out to about 1 clinician with a special interest in heart failure for each 1,000 heart failure patients, not a very reassuring ratio.

The burgeoning numbers of heart failure patients, compared with the relative scarcity of both heart failure experts and general cardiologists, raises issues of how primary-care internists best share this management responsibility. Recent interviews with several heart failure subspecialists and primary care internists provide some insight into how this division of labor is now playing out in routine U.S. practice. What often occurs is that primary care internists take exclusive responsibility for caring for heart failure patients until they feel they are getting in over their heads, at which time they’ll consult with a cardiology colleague or refer the patient to a cardiologist. That moment of recognition by the generalist – that the demands and complexity of the case exceed their comfort level – varies widely, with some PCPs referring patients as soon as heart failure symptoms appear while others stay comfortable as the primary care giver even as a patient’s disease deteriorates to a more advanced stage.

Heart failure specialists highlighted their reliance on PCPs to take an ongoing, active role even for patients with significantly advanced heart failure, as generalists are well suited to coordinating the multispecialty care that such patients usually require, with attention to their need for lifestyle modifications as well as management of their diabetes, sleep apnea, chronic obstructive pulmonary disease, renal failure, and other comorbidities.

Mitchel L. Zoler/Frontline Medical News

As Dr. Michael K. Ong, a primary care internist at the University of California, Los Angeles, said in an interview, his heart failure specialist colleague manages patients’ heart failure; “I manage [or refer] everything else not directly related to the heart failure.”

The most successful U.S. care models seem to be some variation on a team-care approach, in which physicians collaborate with pharmacists, nurses, rehabilitation specialists, and social workers as well as specialists, a team that would include and perhaps be led by either a primary care internist, a cardiologist, or a heart failure specialist but would also broadly include physicians able to deal with all the morbidity facets of heart failure. It’s a model that remains unavailable in many U.S. settings or is just starting to emerge, as fee-for-service coverage of patients gets replaced by population-management models that better accommodate the upfront financial demands of coordinated team care. It makes financial sense a few years down the road when improved patient outcomes result in cost savings.

Primary care and patients with symptomatic heart failure

The heart failure definitions and staging system established in 2001 by a guidelines panel of the American College of Cardiology and American Heart Association defined stage A heart failure as starting before a patient exhibits any heart failure symptoms (the classic ones include dyspnea, rales, and peripheral edema). The panel designated symptomatic heart failure patients as stage C. Patients without heart failure symptoms but with one or more risk factors (such as hypertension, diabetes, obesity, and cardiovascular disease) plus structural heart disease (such as cardiomyopathy or other forms of heart remodeling) were designated stage B. The panel said that people at stage A had one or more risk factors but no structural heart changes and no heart failure symptoms.

Although stage-A heart failure patients are clearly the types of people most often seen and cared for by PCPs, many of these physicians, as well as many heart failure specialists, don’t consider patients who have only hypertension or only diabetes or only obesity as yet having heart failure. That paradox deserves more discussion, but the best way to begin talking about PCPs and heart failure patients is when patients are symptomatic and have what everyone would agree is heart failure.

Even though the ACC/AHA staging system places stage C patients well down the heart failure road, stage C is usually when patients are first diagnosed with heart failure. Although the diagnosis is often first made by a hospitalist or emergency-department physician when severe and sudden-onset heart failure symptoms drive the patient to a hospital, or the diagnosis originates with a cardiologist or heart failure specialist when the patient’s presentation and differential diagnosis isn’t straightforward, most commonly the diagnosis starts with a PCP in an office encounter with a patient who is symptomatic but not acutely ill.

“Patients with shortness of breath or other forms of effort intolerance most often seek care from PCPs. The differential diagnosis of dyspnea is long and complex. Recognition that a patient with dyspnea may have HF is crucial” for timely management and treatment, said Dr. Mary Norine Walsh, medical director of Heart Failure and Cardiac Transplantation at St. Vincent Heart Center in Indianapolis.

At the Mayo Clinic in Rochester, Minn., “most of the heart failure diagnoses are done by PCPs, usually first identified at stage C when a patient comes in with symptoms. Stage B heart failure is usually only identified as an incidental finding when echocardiography is done for some other reason,” said Dr. Paul M. McKie, a heart failure cardiologist who works closely with the primary-care staff at Mayo as an embedded consultant cardiologist.

Mitchel L. Zoler/Frontline Medical News

According to Dr. Mariell L. Jessup, a heart failure physician and professor at the University of Pennsylvania in Philadelphia, a key to PCPs promptly identifying patients with recent-onset, stage C heart failure is to keep the disease as well as its prominent risk factors at the top of their differential-diagnosis list for at-risk patients. “Heart failure is a common disorder,” Dr. Jessup said, and must be considered for patients with shortness of breath. “The leading causes of heart failure are hypertension, obesity, and diabetes. So keep heart failure in mind, especially for patients with one or more of these risk factors.”

Although PCPs might order an echocardiography examination or a lab test like measurement of brain natriuretic protein (BNP) to help nail down the diagnosis, they often leave reading the echocardiography results to a cardiologist colleague. “When a PCP orders an echo it’s automatically read by a cardiologist, and then we get the cardiologist’s report. I don’t read echos myself,” said Dr. Rebecca J. Cunningham, an internal medicine PCP at Brigham and Women’s Hospital in Boston who frequently sees patients with heart failure as medical director of the hospital’s Integrated Care Management Program. “I had one PCP colleague who undertook additional training to learn to read echos himself, but that’s unusual.”

Dr. Mary Ann Bauman, an internal medicine PCP and medical director for Women’s Health and Community Relations at INTEGRIS Health in Oklahoma City, noted a similar division of labor. “If a patient has shortness of breath, maybe some edema, and I hear a few rales, but is totally functional, I always order an echo but I don’t read it. I refer the echo to a cardiologist who then sends me a report,” Dr. Bauman said in an interview. “If I think the patient may have heart failure I’ll also order a BNP or NT-proBNP test. If I suspect heart failure and the BNP is high, it’s a red flag. BNP is another tool for getting the diagnosis right.”

The next step seems much more variable. Some PCPs retain primary control of heart failure management for many of their patients, especially when stage C patients remain stable and functional on simple, straightforward treatment and particularly when they have heart failure with preserved ejection fraction (HFpEF), usually defined as a left ventricular ejection fraction that is at least 40%-45%. Consultation or referral to a cardiologist or heart-failure physician seems much more common for patients with frequent decompensations and hospitalizations or patients with heart failure with reduced ejection fraction (HFrEF). But the main thread reported by both PCPs and cardiologists is that it all depends and varies for each patient and for each PCP depending on what patient responsibilities a PCP feels comfortable taking on.

Dr. Bauman sits at one end of the spectrum: “If it looks like a patient has heart failure, I refer them right away; I don’t wait for decompensation to occur. I want to be sure that there are no nuances in the patient that need something before I recognize it. Most of my PCP partners do the same. You don’t know what it is you don’t know. For me, it’s better to refer the patient right away so the patient has a cardiologist who already knows them who can be called if they start to decompensate.”

Dr. Bauman cited the increasing complexity of heart failure management as the main driver of her current approach, which she contrasted to how she dealt with heart failure patients 20 years ago. “It’s become so complicated that, as a PCP, I don’t feel that I can keep up” with the optimal ways to manage every heart failure patient. “I might not give my heart failure patients the best care they could receive.” The aspects of care that Dr. Bauman said she can provide to heart failure patients she has referred include “dealing with lifestyle changes, making sure patients are taking their medications and getting to their appointments, adjusting their heart-failure medication dosages as needed once they start on the drugs, and seeing that their diabetes and hypertension are well controlled. That is the role of the PCP. But when it comes to deciding which HF medications to use, that’s when I like to have a cardiologist involved.”

But the PCPs at Mayo Clinic often take a different tack, said Dr. McKie. “If the patient is a simple case of heart failure with no red flags and the patient is doing relatively well on treatment with simple diuretic treatment, then initiation of heart failure medications and ongoing management is often directed by the PCP with some cardiology backup as needed,” he said. But Dr. McKie conceded that a spectrum of PCP approaches exists at Mayo as well. “A lot depends on the patient and on the specific provider. Some patients we never get calls about; their PCPs are excellent at managing diuretics and uptitrating beta-blockers and ACE inhibitors. We may only get called if the patient decompensates, But other PCPs are very uncomfortable and they request that we get involved as soon as the diagnosis of stage C heart failure is made. So there is a wide range.” Dr. McKie noted that he thinks it is appropriate for himself or one of his cardiology colleagues to get more active when the HFrEF patient’s ejection fraction drops below 40% and certainly below 35%. That’s because at this stage, patients also need treatment with an aldosterone receptor antagonist such as spironolactone, and they undergo consideration for receiving an implantable cardioverter defibrillator or a cardiac resynchronization therapy device.

Mitchel L. Zoler/Frontline Medical News

“There is nothing magic about heart failure management; it is very well proscribed by guidelines. Nothing precludes a PCP from taking ownership” of heart failure patients, said Dr. Akshay S. Desai, a heart failure cardiologist at Brigham and Women’s Hospital. “I think there is some fear among PCPs that they intrude” by managing heart failure patients. But for patients with structural heart disease or even left ventricular dysfunction, “PCPs should feel empowered to start standard heart failure treatments, including ACE inhibitors and beta-blockers, especially because half of heart failure patients have HFpEF, and PCPs often don’t refer HFpEF patients to cardiologists. It’s the patients with left ventricular dysfunction who end up in heart failure clinics,” Dr. Desai said.

On the other hand, Dr. Desai cautioned PCPs against waiting too long to bring more complex, sicker, and harder-to-manage patients to the attention of a heart failure specialist.

“What we worry about are late referrals, when patients are profoundly decompensated,” he said. “By the time they show up [at a heart failure clinic or emergency department] they have end-organ dysfunction,” which makes them much harder to treat and maybe irreversible. “Recognizing heart failure early is the key, and early referral is an obligation” when a heart failure patient is deteriorating or becomes too complex for a PCP to properly manage, Dr. Desai advised.

But even when heart failure patients develop more severe disease, with significantly depressed left ventricular function or frequent decompensations, PCPs continue to play a valuable role in coordinating the wide range of treatments patients need for their various comorbidities.

“Once a cardiologist or heart failure physician is involved there is still a role for PCPs” said Dr. Monica R. Shah, deputy chief of the Heart Failure and Arrhythmia Branch of the National Heart, Lung, and Blood Institute in Bethesda, Md. “Heart failure patients are complex, it’s not just one organ system that’s affected, and you need a partnership between cardiologists and PCPs to coordinate all of a patient’s care. A heart failure physician needs to work with a PCP to be sure that the patient’s health is optimal. Collaboration between cardiologists and PCPs is key to ensure that optimal care is effectively delivered to patients,” Dr. Shah said in an interview.

“Keeping the PCP at the center of the care team is critical, especially with the multiple comorbidities that HF patients can have, including chronic obstructive pulmonary disease, diabetes, renal failure, sleep apnea, atrial fibrillation, and degenerative joint disease. Before you know it you have a half-dozen subspecialists involved in care and it can become uncoordinated. Keeping the PCP at the center of the team and providing the PCP with support from specialists as needed is critical,” said Dr. McKie.

Even for the most severe heart failure patients, PCPs can still play an important role by providing palliative care and dealing with end-of-life issues, specialists said.

Primary care and heart failure’s antecedents

The other, obvious time in heart failure’s severity spectrum for PCPs to take a very active role is with presymptomatic, stage A patients. Perhaps the only controversial element of this is whether such patients really have a form of heart failure and whether is it important to conceptualize heart failure this way.

The notion of stage A heart failure dates back to the 2001 edition of heart failure diagnosis and management recommendations issued by a panel organized by the ACC and AHA (J Am Coll Cardiol. 2001 Dec;38[7]:2101-13). The 2001 writing committee members said that they “decided to take a new approach to the classification of heart failure that emphasized both the evolution and progression of the disease.” They defined stage A patients as presymptomatic and without structural heart disease but with “conditions strongly associated with the development of heart failure,” specifically systemic hypertension, coronary artery disease, diabetes, a history of cardiotoxic drug therapy or alcohol abuse, a history of rheumatic fever, or a family history of cardiomyopathy.

When the ACC and AHA panel members next updated the heart failure recommendations in 2005, they seemed to take a rhetorical step back, saying that stage A and B “are clearly not heart failure but are an attempt to help healthcare providers identify patients early who are at risk for developing heart failure. Stage A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF.” (J Am Coll Cardiol. 2005 Sept. 46[6]:1116-43) In 2005, the panel also streamlined the list of risk factors that identify stage A heart failure patients: hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, patients who have taken cardiotoxins, or patients with a family history of cardiomyopathy. The 2009 recommendation update left this definition of stage A heart failure unchanged, but in 2013 the most recent update devoted less attention to explaining the significance of the stage-A heart failure, although it clearly highlighted the importance of controlling hypertension, diabetes, and obesity as ways to prevent patients from developing symptomatic heart failure (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-e239).

The subtle, official tweaking of the stage A (and B) heart failure concept during 2001-2013, as well establishment of stage A in the first place, seems to have left both PCPs and heart failure specialists unsure on exactly how to think about presymptomatic people with one or more of the prominent heart failure risk factors of hypertension, diabetes, and obesity. While they uniformly agree that identifying these risk factors and then treating them according to contemporary guidelines is hugely important for stopping or deferring the onset of heart failure, and they also agree that this aspect of patient care is clearly a core responsibility for PCPs, many also say that they don’t think of presymptomatic patients as having heart failure of any type despite the stage A designation on the books.

One exception is St. Vincent’s Dr. Walsh. “I think the writers of the 2001 heart failure guidelines had an inspired approach. Identifying patients with hypertension, diabetes, coronary artery disease, etc., as patients with heart failure has helped drive home the point that treatment and control of these diseases is crucial,” she said in an interview. “But I am not sure all physicians have adopted the concept. “Uncontrolled hypertension is prevalent, and not viewed by all as resulting in heart failure down the road. Diabetes and hypertension are very important risk factors for the development of heart failure in women,” she added. “I’m especially diligent in ensuring that women with one or both of these diseases get treated aggressively.”

Highlighting specifically the fundamental role that uncontrolled hypertension plays in causing heart failure, the University of Pennsylvania’s Dr. Jessup estimated that controlling hypertension throughout the U.S. population could probably cut heart failure incidence in half.

Others draw a sharper contrast between the risk factor stage and the symptomatic stages of heart failure, though they all agree on the importance of risk factor management by PCPs. “Hypertension does not mean that a patient has heart failure; it means they have a risk factor for heart failure and the patient is in the prevention stage,” said the NHLBI’s Dr. Shah. ”The most important role for PCPs is to identify the risk factors and prevent development of [symptomatic] heart failure. This is where PCPs are critically important because patients present to them at the early stages.”

Dr. Bauman, the PCP with INTEGRIS in Oklahoma City, generally doesn’t conflate risk factors with stage A heart failure. “I look at every patient with hypertension or diabetes as a person at risk for cardiovascular disease. I push them to get their blood pressure and glycemia under control. But I don’t think of them as stage A heart failure patients. I think of them as patients at risk for heart failure, but also at risk for atrial fibrillation, MI, and stroke. I think about their risk, but I don’t label them in my mind as having stage A heart failure. I think that this is a patient at risk for cardiovascular disease and that I must do what I should to manage their risk factors.”

“I don’t personally think about patients having stage A heart failure,” agreed Dr. Cunningham, a PCP at Brigham and Women’s Hospital. “When I see patients with hypertension, I counsel them about what matters to them so that they will take their medications, because if they currently feel fine they may not understand the long-term risk they face. So I invest time in making the patient understand why their hypertension is important and the risks it poses, so that in the long-run they won’t have a stroke or MI or develop heart failure. But I don’t think that the stage A definition has changed my approach; I already think of hypertension as a precursor to a variety of bad downstream consequences. I don’t think of someone as a heart failure patient just because they have hypertension, and I don’t think that every patient with hypertension will develop heart failure.” Speaking of her colleagues, Dr. Cunningham added, “I don’t have a sense that the stages of heart failure have made much of an impact on how other PCPs talk with patients or plan their care.”

“The heart failure staging system is useful from the standpoint of emphasizing that the disease begins with primordial risk and progresses through a period of structural injury during which patients may not be symptomatic,” summed up Dr. Desai. “But practically, most of us confront the diagnosis of heart failure when patients become symptomatic and reach stage C.”

Can an intensified approach better slow stage A progression?

One of the inherent limitations right now in referring to patients as having stage A heart failure is that it adds little to how heart failure risk factors are managed. A patient with hypertension undergoing appropriate care will receive treatment to lower blood pressure to recommended goal levels. The antihypertensive treatment remains the same regardless of whether the patient is considered to have only hypertension or whether the treating physician also thinks of the patient as having stage A heart failure. The same applies to patients diagnosed with diabetes; their hyperglycemia-controlling treatment remains unchanged whether or not their physician labels them as stage A heart failure patients.

But what if an evidence-based way existed to not only identify patients with hypertension or diabetes, but to identify within those patients the subset who faced a particularly increased risk for developing heart failure? And what if an evidence-based intervention existed that could be added to standard blood pressure–lowering or hyperglycemia-controlling interventions and had proved to slow or stop progression of patients to heart failure?

Preliminary evidence that screening for stage A heart failure patients can successfully identify a subset at elevated risk for developing symptomatic heart failure and that intensified risk-factor control helped mitigate this risk appeared in two reports published in 2013. But both studies were relatively small, they ran in Europe, and neither has undergone replication in a U.S. study in the 2.5 years since their publication.

The larger study, STOP-HF (St. Vincent’s Screening to Prevent Heart Failure), included patients at 39 primary care practices in Ireland, a study organized by researchers at St. Vincent’s University Hospital in Dublin. They enrolled people without symptoms of heart failure who were at least 41 years old and had at least one of these risk factors: hypertension, hypercholesterolemia, obesity, vascular disease, diabetes, an arrhythmia, or valvular disease: In short, primarily stage A heart failure patients.

The researchers then tested 1,374 of these people for their baseline blood level of BNP and randomized them into two intervention arms. For those randomized to the active arm, the PCPs for these people received an unblinded report of the BNP results, and those with a level of 50 pg/mL or higher underwent further assessment by screening echocardiography and intensified risk-factor control, including risk-factor coaching by a nurse. Those randomized to this arm who had a lower BNP level at baseline underwent annual follow-up BNP screening, and if their level reached the 50 pg/ML threshold they switched to the more intensified protocol. Those randomized to the control arm received a more standard program of risk-factor modification and their BNP levels were never unblinded.

After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).

The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).

Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.

“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.

“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.

She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.

“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”

The economic barrier to intensified stage-A management

Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.

“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.

“This speaks to the need for more population-based preventive management, which PCPs are trying to start to do, but currently we are nowhere near fulfilling that potential,” said Dr. Cunningham. The barrier is having clinical resources for help in managing lower-risk patients, to make sure they receive all the interventions they should. We’re now trying to start using care teams for patients with diabetes or other conditions. The biggest gap is that we don’t have the resources; we don’t have enough nurses on our staff to intervene” for all the patients who could potentially benefit. “Right now, we can only afford to use nurses for selected, high-risk patients.” The challenge is to have a care model that allows a lot of upfront costs to generate savings over a long-term time horizon, he said. “It’s very important for improving population health, but it’s hard to make it happen in our current health care system.”

Dr. Ahmad noted the enormous downside of a health system that is not proactive and often waits for heart failure patients to declare themselves with severe illness.

“The majority of heart failure patients I see drifted through the health care system” without recognition of their accumulating morbidity. “By the time they show heart failure symptoms, their disease is pretty advanced and we have real difficulty managing it. A lot of patients do not have their heart failure managed until they fall off the edge and their condition is much less modifiable. If we could identify these patients sooner, it would help both them and the health care system. It would be great to have objective measures that could help PCPs identify early abnormal patients who need more aggressive management. In much of U.S. practice, heart failure management is more specialty driven. It might be different in closed systems, but in many heart failure practices there is no PCP coordination. The health care system is not set up to allow PCPs to take care of these issues.”

Dr. Bauman said she sees some reason for optimism in looming reimbursement changes, where population management might help drive a shift toward more team care for heart failure and a focus on earlier identification of patients at risk and intervention at early stages of their disease.

“As we move toward population management it becomes more obvious that you need a team approach to managing heart failure, involving not just physicians but also pharmacists, nurses, social workers, and care coordinators. In my system, INTEGRIS, the whole-team management approach is beginning to happen. It’s new to primary care to apply a large team of clinicians; it takes a lot of resources. Being able to afford a team was a problem when we were paid by fee-for-service, it wasn’t practical. Population management will make it possible.”

Dr. Desai has been a consultant to Novartis, Merck, St. Jude, and Relypsa and has received research funding from Novartis and AtCor Medical. Dr. Redfield has been a consultant to Merck and Eli Lilly. Dr. Ahmad has been a consultant to Roche. Dr. Ong, Dr. Walsh, Dr. Jessup, Dr. McKie, Dr. Bauman, Dr. Shah, and Dr. Cunningham had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure management has become increasingly complex over the past couple of decades, with new drugs and drug combinations, new uses for potentially life-saving implanted devices, and a more sophisticated appreciation of the ways that various comorbidities complicate a heart failure patient’s clinical status. These expanded dimensions of heart failure care resulted in the establishment in 2008 of a new secondary subspecialty, Advanced Heart Failure and Transplant Cardiology, aimed at training and certifying physicians in all the nuances of complex heart failure diagnostics and care.

But as the 2009 manifesto announcing this new heart failure subspecialty detailed, care for the vast majority of U.S. patients with heart failure remains in the hands of internal medicine primary care physicians (PCPs) and general cardiologists (J Am Coll Cardiol. 2009 Mar 10;53[10]:834-6). To some extent this is a manpower issue. The estimated number of Americans living with heart failure exceeds 5 million, a figure that dwarfs the very modest number of U.S. physicians and clinicians who are certified or self-identified heart failure specialists.

As of today, fewer than 1,000 U.S. physicians have received formal certification as heart failure subspecialists through the examination administered in 2010, 2012, and 2014, said Michele Blair, chief executive officer of the Heart Failure Society of America. A more liberal definition of a heart failure specialist might include the roughly 3,000 unique physicians (mostly cardiologists, but also some hospitalists and emergency physicians) who have recently attended an annual meeting of the HFSA, as well as the roughly 2,300 physician assistants and nurse practitioners who have shown a heart failure interest by coming to a recent HFSA meeting. But even these expanded estimates calculate out to about 1 clinician with a special interest in heart failure for each 1,000 heart failure patients, not a very reassuring ratio.

The burgeoning numbers of heart failure patients, compared with the relative scarcity of both heart failure experts and general cardiologists, raises issues of how primary-care internists best share this management responsibility. Recent interviews with several heart failure subspecialists and primary care internists provide some insight into how this division of labor is now playing out in routine U.S. practice. What often occurs is that primary care internists take exclusive responsibility for caring for heart failure patients until they feel they are getting in over their heads, at which time they’ll consult with a cardiology colleague or refer the patient to a cardiologist. That moment of recognition by the generalist – that the demands and complexity of the case exceed their comfort level – varies widely, with some PCPs referring patients as soon as heart failure symptoms appear while others stay comfortable as the primary care giver even as a patient’s disease deteriorates to a more advanced stage.

Heart failure specialists highlighted their reliance on PCPs to take an ongoing, active role even for patients with significantly advanced heart failure, as generalists are well suited to coordinating the multispecialty care that such patients usually require, with attention to their need for lifestyle modifications as well as management of their diabetes, sleep apnea, chronic obstructive pulmonary disease, renal failure, and other comorbidities.

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As Dr. Michael K. Ong, a primary care internist at the University of California, Los Angeles, said in an interview, his heart failure specialist colleague manages patients’ heart failure; “I manage [or refer] everything else not directly related to the heart failure.”

The most successful U.S. care models seem to be some variation on a team-care approach, in which physicians collaborate with pharmacists, nurses, rehabilitation specialists, and social workers as well as specialists, a team that would include and perhaps be led by either a primary care internist, a cardiologist, or a heart failure specialist but would also broadly include physicians able to deal with all the morbidity facets of heart failure. It’s a model that remains unavailable in many U.S. settings or is just starting to emerge, as fee-for-service coverage of patients gets replaced by population-management models that better accommodate the upfront financial demands of coordinated team care. It makes financial sense a few years down the road when improved patient outcomes result in cost savings.

Primary care and patients with symptomatic heart failure

The heart failure definitions and staging system established in 2001 by a guidelines panel of the American College of Cardiology and American Heart Association defined stage A heart failure as starting before a patient exhibits any heart failure symptoms (the classic ones include dyspnea, rales, and peripheral edema). The panel designated symptomatic heart failure patients as stage C. Patients without heart failure symptoms but with one or more risk factors (such as hypertension, diabetes, obesity, and cardiovascular disease) plus structural heart disease (such as cardiomyopathy or other forms of heart remodeling) were designated stage B. The panel said that people at stage A had one or more risk factors but no structural heart changes and no heart failure symptoms.

Although stage-A heart failure patients are clearly the types of people most often seen and cared for by PCPs, many of these physicians, as well as many heart failure specialists, don’t consider patients who have only hypertension or only diabetes or only obesity as yet having heart failure. That paradox deserves more discussion, but the best way to begin talking about PCPs and heart failure patients is when patients are symptomatic and have what everyone would agree is heart failure.

Even though the ACC/AHA staging system places stage C patients well down the heart failure road, stage C is usually when patients are first diagnosed with heart failure. Although the diagnosis is often first made by a hospitalist or emergency-department physician when severe and sudden-onset heart failure symptoms drive the patient to a hospital, or the diagnosis originates with a cardiologist or heart failure specialist when the patient’s presentation and differential diagnosis isn’t straightforward, most commonly the diagnosis starts with a PCP in an office encounter with a patient who is symptomatic but not acutely ill.

“Patients with shortness of breath or other forms of effort intolerance most often seek care from PCPs. The differential diagnosis of dyspnea is long and complex. Recognition that a patient with dyspnea may have HF is crucial” for timely management and treatment, said Dr. Mary Norine Walsh, medical director of Heart Failure and Cardiac Transplantation at St. Vincent Heart Center in Indianapolis.

At the Mayo Clinic in Rochester, Minn., “most of the heart failure diagnoses are done by PCPs, usually first identified at stage C when a patient comes in with symptoms. Stage B heart failure is usually only identified as an incidental finding when echocardiography is done for some other reason,” said Dr. Paul M. McKie, a heart failure cardiologist who works closely with the primary-care staff at Mayo as an embedded consultant cardiologist.

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According to Dr. Mariell L. Jessup, a heart failure physician and professor at the University of Pennsylvania in Philadelphia, a key to PCPs promptly identifying patients with recent-onset, stage C heart failure is to keep the disease as well as its prominent risk factors at the top of their differential-diagnosis list for at-risk patients. “Heart failure is a common disorder,” Dr. Jessup said, and must be considered for patients with shortness of breath. “The leading causes of heart failure are hypertension, obesity, and diabetes. So keep heart failure in mind, especially for patients with one or more of these risk factors.”

Although PCPs might order an echocardiography examination or a lab test like measurement of brain natriuretic protein (BNP) to help nail down the diagnosis, they often leave reading the echocardiography results to a cardiologist colleague. “When a PCP orders an echo it’s automatically read by a cardiologist, and then we get the cardiologist’s report. I don’t read echos myself,” said Dr. Rebecca J. Cunningham, an internal medicine PCP at Brigham and Women’s Hospital in Boston who frequently sees patients with heart failure as medical director of the hospital’s Integrated Care Management Program. “I had one PCP colleague who undertook additional training to learn to read echos himself, but that’s unusual.”

Dr. Mary Ann Bauman, an internal medicine PCP and medical director for Women’s Health and Community Relations at INTEGRIS Health in Oklahoma City, noted a similar division of labor. “If a patient has shortness of breath, maybe some edema, and I hear a few rales, but is totally functional, I always order an echo but I don’t read it. I refer the echo to a cardiologist who then sends me a report,” Dr. Bauman said in an interview. “If I think the patient may have heart failure I’ll also order a BNP or NT-proBNP test. If I suspect heart failure and the BNP is high, it’s a red flag. BNP is another tool for getting the diagnosis right.”

The next step seems much more variable. Some PCPs retain primary control of heart failure management for many of their patients, especially when stage C patients remain stable and functional on simple, straightforward treatment and particularly when they have heart failure with preserved ejection fraction (HFpEF), usually defined as a left ventricular ejection fraction that is at least 40%-45%. Consultation or referral to a cardiologist or heart-failure physician seems much more common for patients with frequent decompensations and hospitalizations or patients with heart failure with reduced ejection fraction (HFrEF). But the main thread reported by both PCPs and cardiologists is that it all depends and varies for each patient and for each PCP depending on what patient responsibilities a PCP feels comfortable taking on.

Dr. Bauman sits at one end of the spectrum: “If it looks like a patient has heart failure, I refer them right away; I don’t wait for decompensation to occur. I want to be sure that there are no nuances in the patient that need something before I recognize it. Most of my PCP partners do the same. You don’t know what it is you don’t know. For me, it’s better to refer the patient right away so the patient has a cardiologist who already knows them who can be called if they start to decompensate.”

Dr. Bauman cited the increasing complexity of heart failure management as the main driver of her current approach, which she contrasted to how she dealt with heart failure patients 20 years ago. “It’s become so complicated that, as a PCP, I don’t feel that I can keep up” with the optimal ways to manage every heart failure patient. “I might not give my heart failure patients the best care they could receive.” The aspects of care that Dr. Bauman said she can provide to heart failure patients she has referred include “dealing with lifestyle changes, making sure patients are taking their medications and getting to their appointments, adjusting their heart-failure medication dosages as needed once they start on the drugs, and seeing that their diabetes and hypertension are well controlled. That is the role of the PCP. But when it comes to deciding which HF medications to use, that’s when I like to have a cardiologist involved.”

But the PCPs at Mayo Clinic often take a different tack, said Dr. McKie. “If the patient is a simple case of heart failure with no red flags and the patient is doing relatively well on treatment with simple diuretic treatment, then initiation of heart failure medications and ongoing management is often directed by the PCP with some cardiology backup as needed,” he said. But Dr. McKie conceded that a spectrum of PCP approaches exists at Mayo as well. “A lot depends on the patient and on the specific provider. Some patients we never get calls about; their PCPs are excellent at managing diuretics and uptitrating beta-blockers and ACE inhibitors. We may only get called if the patient decompensates, But other PCPs are very uncomfortable and they request that we get involved as soon as the diagnosis of stage C heart failure is made. So there is a wide range.” Dr. McKie noted that he thinks it is appropriate for himself or one of his cardiology colleagues to get more active when the HFrEF patient’s ejection fraction drops below 40% and certainly below 35%. That’s because at this stage, patients also need treatment with an aldosterone receptor antagonist such as spironolactone, and they undergo consideration for receiving an implantable cardioverter defibrillator or a cardiac resynchronization therapy device.

Mitchel L. Zoler/Frontline Medical News

“There is nothing magic about heart failure management; it is very well proscribed by guidelines. Nothing precludes a PCP from taking ownership” of heart failure patients, said Dr. Akshay S. Desai, a heart failure cardiologist at Brigham and Women’s Hospital. “I think there is some fear among PCPs that they intrude” by managing heart failure patients. But for patients with structural heart disease or even left ventricular dysfunction, “PCPs should feel empowered to start standard heart failure treatments, including ACE inhibitors and beta-blockers, especially because half of heart failure patients have HFpEF, and PCPs often don’t refer HFpEF patients to cardiologists. It’s the patients with left ventricular dysfunction who end up in heart failure clinics,” Dr. Desai said.

On the other hand, Dr. Desai cautioned PCPs against waiting too long to bring more complex, sicker, and harder-to-manage patients to the attention of a heart failure specialist.

“What we worry about are late referrals, when patients are profoundly decompensated,” he said. “By the time they show up [at a heart failure clinic or emergency department] they have end-organ dysfunction,” which makes them much harder to treat and maybe irreversible. “Recognizing heart failure early is the key, and early referral is an obligation” when a heart failure patient is deteriorating or becomes too complex for a PCP to properly manage, Dr. Desai advised.

But even when heart failure patients develop more severe disease, with significantly depressed left ventricular function or frequent decompensations, PCPs continue to play a valuable role in coordinating the wide range of treatments patients need for their various comorbidities.

“Once a cardiologist or heart failure physician is involved there is still a role for PCPs” said Dr. Monica R. Shah, deputy chief of the Heart Failure and Arrhythmia Branch of the National Heart, Lung, and Blood Institute in Bethesda, Md. “Heart failure patients are complex, it’s not just one organ system that’s affected, and you need a partnership between cardiologists and PCPs to coordinate all of a patient’s care. A heart failure physician needs to work with a PCP to be sure that the patient’s health is optimal. Collaboration between cardiologists and PCPs is key to ensure that optimal care is effectively delivered to patients,” Dr. Shah said in an interview.

“Keeping the PCP at the center of the care team is critical, especially with the multiple comorbidities that HF patients can have, including chronic obstructive pulmonary disease, diabetes, renal failure, sleep apnea, atrial fibrillation, and degenerative joint disease. Before you know it you have a half-dozen subspecialists involved in care and it can become uncoordinated. Keeping the PCP at the center of the team and providing the PCP with support from specialists as needed is critical,” said Dr. McKie.

Even for the most severe heart failure patients, PCPs can still play an important role by providing palliative care and dealing with end-of-life issues, specialists said.

Primary care and heart failure’s antecedents

The other, obvious time in heart failure’s severity spectrum for PCPs to take a very active role is with presymptomatic, stage A patients. Perhaps the only controversial element of this is whether such patients really have a form of heart failure and whether is it important to conceptualize heart failure this way.

The notion of stage A heart failure dates back to the 2001 edition of heart failure diagnosis and management recommendations issued by a panel organized by the ACC and AHA (J Am Coll Cardiol. 2001 Dec;38[7]:2101-13). The 2001 writing committee members said that they “decided to take a new approach to the classification of heart failure that emphasized both the evolution and progression of the disease.” They defined stage A patients as presymptomatic and without structural heart disease but with “conditions strongly associated with the development of heart failure,” specifically systemic hypertension, coronary artery disease, diabetes, a history of cardiotoxic drug therapy or alcohol abuse, a history of rheumatic fever, or a family history of cardiomyopathy.

When the ACC and AHA panel members next updated the heart failure recommendations in 2005, they seemed to take a rhetorical step back, saying that stage A and B “are clearly not heart failure but are an attempt to help healthcare providers identify patients early who are at risk for developing heart failure. Stage A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF.” (J Am Coll Cardiol. 2005 Sept. 46[6]:1116-43) In 2005, the panel also streamlined the list of risk factors that identify stage A heart failure patients: hypertension, atherosclerotic disease, diabetes, obesity, metabolic syndrome, patients who have taken cardiotoxins, or patients with a family history of cardiomyopathy. The 2009 recommendation update left this definition of stage A heart failure unchanged, but in 2013 the most recent update devoted less attention to explaining the significance of the stage-A heart failure, although it clearly highlighted the importance of controlling hypertension, diabetes, and obesity as ways to prevent patients from developing symptomatic heart failure (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-e239).

The subtle, official tweaking of the stage A (and B) heart failure concept during 2001-2013, as well establishment of stage A in the first place, seems to have left both PCPs and heart failure specialists unsure on exactly how to think about presymptomatic people with one or more of the prominent heart failure risk factors of hypertension, diabetes, and obesity. While they uniformly agree that identifying these risk factors and then treating them according to contemporary guidelines is hugely important for stopping or deferring the onset of heart failure, and they also agree that this aspect of patient care is clearly a core responsibility for PCPs, many also say that they don’t think of presymptomatic patients as having heart failure of any type despite the stage A designation on the books.

One exception is St. Vincent’s Dr. Walsh. “I think the writers of the 2001 heart failure guidelines had an inspired approach. Identifying patients with hypertension, diabetes, coronary artery disease, etc., as patients with heart failure has helped drive home the point that treatment and control of these diseases is crucial,” she said in an interview. “But I am not sure all physicians have adopted the concept. “Uncontrolled hypertension is prevalent, and not viewed by all as resulting in heart failure down the road. Diabetes and hypertension are very important risk factors for the development of heart failure in women,” she added. “I’m especially diligent in ensuring that women with one or both of these diseases get treated aggressively.”

Highlighting specifically the fundamental role that uncontrolled hypertension plays in causing heart failure, the University of Pennsylvania’s Dr. Jessup estimated that controlling hypertension throughout the U.S. population could probably cut heart failure incidence in half.

Others draw a sharper contrast between the risk factor stage and the symptomatic stages of heart failure, though they all agree on the importance of risk factor management by PCPs. “Hypertension does not mean that a patient has heart failure; it means they have a risk factor for heart failure and the patient is in the prevention stage,” said the NHLBI’s Dr. Shah. ”The most important role for PCPs is to identify the risk factors and prevent development of [symptomatic] heart failure. This is where PCPs are critically important because patients present to them at the early stages.”

Dr. Bauman, the PCP with INTEGRIS in Oklahoma City, generally doesn’t conflate risk factors with stage A heart failure. “I look at every patient with hypertension or diabetes as a person at risk for cardiovascular disease. I push them to get their blood pressure and glycemia under control. But I don’t think of them as stage A heart failure patients. I think of them as patients at risk for heart failure, but also at risk for atrial fibrillation, MI, and stroke. I think about their risk, but I don’t label them in my mind as having stage A heart failure. I think that this is a patient at risk for cardiovascular disease and that I must do what I should to manage their risk factors.”

“I don’t personally think about patients having stage A heart failure,” agreed Dr. Cunningham, a PCP at Brigham and Women’s Hospital. “When I see patients with hypertension, I counsel them about what matters to them so that they will take their medications, because if they currently feel fine they may not understand the long-term risk they face. So I invest time in making the patient understand why their hypertension is important and the risks it poses, so that in the long-run they won’t have a stroke or MI or develop heart failure. But I don’t think that the stage A definition has changed my approach; I already think of hypertension as a precursor to a variety of bad downstream consequences. I don’t think of someone as a heart failure patient just because they have hypertension, and I don’t think that every patient with hypertension will develop heart failure.” Speaking of her colleagues, Dr. Cunningham added, “I don’t have a sense that the stages of heart failure have made much of an impact on how other PCPs talk with patients or plan their care.”

“The heart failure staging system is useful from the standpoint of emphasizing that the disease begins with primordial risk and progresses through a period of structural injury during which patients may not be symptomatic,” summed up Dr. Desai. “But practically, most of us confront the diagnosis of heart failure when patients become symptomatic and reach stage C.”

Can an intensified approach better slow stage A progression?

One of the inherent limitations right now in referring to patients as having stage A heart failure is that it adds little to how heart failure risk factors are managed. A patient with hypertension undergoing appropriate care will receive treatment to lower blood pressure to recommended goal levels. The antihypertensive treatment remains the same regardless of whether the patient is considered to have only hypertension or whether the treating physician also thinks of the patient as having stage A heart failure. The same applies to patients diagnosed with diabetes; their hyperglycemia-controlling treatment remains unchanged whether or not their physician labels them as stage A heart failure patients.

But what if an evidence-based way existed to not only identify patients with hypertension or diabetes, but to identify within those patients the subset who faced a particularly increased risk for developing heart failure? And what if an evidence-based intervention existed that could be added to standard blood pressure–lowering or hyperglycemia-controlling interventions and had proved to slow or stop progression of patients to heart failure?

Preliminary evidence that screening for stage A heart failure patients can successfully identify a subset at elevated risk for developing symptomatic heart failure and that intensified risk-factor control helped mitigate this risk appeared in two reports published in 2013. But both studies were relatively small, they ran in Europe, and neither has undergone replication in a U.S. study in the 2.5 years since their publication.

The larger study, STOP-HF (St. Vincent’s Screening to Prevent Heart Failure), included patients at 39 primary care practices in Ireland, a study organized by researchers at St. Vincent’s University Hospital in Dublin. They enrolled people without symptoms of heart failure who were at least 41 years old and had at least one of these risk factors: hypertension, hypercholesterolemia, obesity, vascular disease, diabetes, an arrhythmia, or valvular disease: In short, primarily stage A heart failure patients.

The researchers then tested 1,374 of these people for their baseline blood level of BNP and randomized them into two intervention arms. For those randomized to the active arm, the PCPs for these people received an unblinded report of the BNP results, and those with a level of 50 pg/mL or higher underwent further assessment by screening echocardiography and intensified risk-factor control, including risk-factor coaching by a nurse. Those randomized to this arm who had a lower BNP level at baseline underwent annual follow-up BNP screening, and if their level reached the 50 pg/ML threshold they switched to the more intensified protocol. Those randomized to the control arm received a more standard program of risk-factor modification and their BNP levels were never unblinded.

After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).

The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).

Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.

“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.

“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.

She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.

“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”

The economic barrier to intensified stage-A management

Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.

“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.

“This speaks to the need for more population-based preventive management, which PCPs are trying to start to do, but currently we are nowhere near fulfilling that potential,” said Dr. Cunningham. The barrier is having clinical resources for help in managing lower-risk patients, to make sure they receive all the interventions they should. We’re now trying to start using care teams for patients with diabetes or other conditions. The biggest gap is that we don’t have the resources; we don’t have enough nurses on our staff to intervene” for all the patients who could potentially benefit. “Right now, we can only afford to use nurses for selected, high-risk patients.” The challenge is to have a care model that allows a lot of upfront costs to generate savings over a long-term time horizon, he said. “It’s very important for improving population health, but it’s hard to make it happen in our current health care system.”

Dr. Ahmad noted the enormous downside of a health system that is not proactive and often waits for heart failure patients to declare themselves with severe illness.

“The majority of heart failure patients I see drifted through the health care system” without recognition of their accumulating morbidity. “By the time they show heart failure symptoms, their disease is pretty advanced and we have real difficulty managing it. A lot of patients do not have their heart failure managed until they fall off the edge and their condition is much less modifiable. If we could identify these patients sooner, it would help both them and the health care system. It would be great to have objective measures that could help PCPs identify early abnormal patients who need more aggressive management. In much of U.S. practice, heart failure management is more specialty driven. It might be different in closed systems, but in many heart failure practices there is no PCP coordination. The health care system is not set up to allow PCPs to take care of these issues.”

Dr. Bauman said she sees some reason for optimism in looming reimbursement changes, where population management might help drive a shift toward more team care for heart failure and a focus on earlier identification of patients at risk and intervention at early stages of their disease.

“As we move toward population management it becomes more obvious that you need a team approach to managing heart failure, involving not just physicians but also pharmacists, nurses, social workers, and care coordinators. In my system, INTEGRIS, the whole-team management approach is beginning to happen. It’s new to primary care to apply a large team of clinicians; it takes a lot of resources. Being able to afford a team was a problem when we were paid by fee-for-service, it wasn’t practical. Population management will make it possible.”

Dr. Desai has been a consultant to Novartis, Merck, St. Jude, and Relypsa and has received research funding from Novartis and AtCor Medical. Dr. Redfield has been a consultant to Merck and Eli Lilly. Dr. Ahmad has been a consultant to Roche. Dr. Ong, Dr. Walsh, Dr. Jessup, Dr. McKie, Dr. Bauman, Dr. Shah, and Dr. Cunningham had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SNOWMASS, COLO. – By far the most-important contributor to improved outcomes following out-of-hospital cardiac arrest during the past decade has been therapeutic hypothermia, Dr. N.A. Mark Estes III said at the Annual Cardiovascular Conference at Snowmass.

The No. 1 cause of in-hospital death in patients who arrive at the hospital with a perfusable rhythm following resuscitation from out-of-hospital cardiac arrest isn’t sepsis, hepatic or renal failure, or cardiogenic shock. It’s neurologic death caused by anoxic brain injury, which begins several hours after cardiac arrest and continues for about 48 hours. This is where therapeutic hypothermia has made a huge difference, said Dr. Estes, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

“One-half of out-of-hospital cardiac arrest survivors experience secondary anoxic brain damage of varying degrees. Until recently, there was no treatment with documented efficacy in preventing this damage. Despite multiple agents being looked at for neuroprevention, none really has worked. But therapeutic hypothermia has drastically improved outcomes. More than half of patients who arrive at the hospital with a perfusable rhythm and receive therapeutic hypothermia are discharged relatively neurologically intact. That’s a huge difference from what we used to see,” the electrophysiologist observed.

Indeed, the proportion of U.S. patients who experience out-of-hospital cardiac arrest and survive to hospital discharge neurologically intact is “dismal” at about 10%, he noted.

Virtually all specialized cardiac arrest centers now provide therapeutic hypothermia using various protocols. The demonstrated effectiveness of this postresuscitation therapy was an impetus for the American Heart Association policy statement calling for creation of regional cardiac resuscitation systems of care (Circulation. 2010 Feb 9;121[5]:709-29). To date, however, such organized systems exist in only a handful of states or portions of states.

Nonetheless, when an out-of-hospital cardiac arrest patient arrives at a community hospital that can’t provide emergency coronary angiography and therapeutic hypothermia, it’s appropriate to stabilize that patient in the emergency department and then transfer to a hospital that can, according to Dr. Estes.

The mechanism by which therapeutic hypothermia works has been well elucidated. The treatment curbs the process by which ischemia as a second blow triggers formation of oxygen free radicals, glutamate release, calcium shifts, and mitochondrial dysfunction, with resultant destruction of brain tissue.

Roughly 250,000 sudden cardiac deaths (SCDs) occur annually in this country. In addition to more widespread availability of therapeutic hypothermia and other forms of specialized postresuscitation care through creation of regional systems of care for out-of-hospital cardiac arrest, there are other opportunities for improving outcomes. These include earlier activation of the chain of survival that begins with a bystander dialing 911 as well as greater availability of public access defibrillation.

Dr. Estes emphasized that while these measures will further improve outcomes of cardiac arrest, they won’t actually reduce its frequency. By far the greatest opportunity in that realm lies in primordial prevention of coronary artery disease; that is, prevention of the risk factors for CAD. After all, he noted, 80% of all SCDs are associated with underlying ischemic heart disease. In 30% of SCDs, the fatal event is the first manifestation of previously unrecognized CAD. Another one-third of SCDs occur in patients with known CAD, but who weren’t considered at high risk for SCD because of their preserved left ventricular ejection fraction.

“There are a number of luminaries in the field who feel that if we’re really going to make an impact on sudden cardiac death, it’s going to be through primordial prevention of CAD,” the cardiologist said.

For this reason, he was thrilled to hear Dr. Robert A. Vogel elsewhere at the conference describe research by investigators at Affiris AG in Vienna who’ve created a peptide-based vaccine that inhibits PCSK9. Moreover, they showed it to be effective in sharply lowering LDL in mice (PLoS One. 2014 Dec 4;9[12]:e114469).

“I believe that in my lifetime, we will have an antiatherosclerotic vaccine that will lower LDL to an extent where this disease will not disappear but may get to a manageable extent, perhaps a 10% lifetime risk instead of the 55% lifetime risk of MI or stroke that we as Americans currently have,” predicted Dr. Vogel of the University of Colorado, Denver.

Dr. Vogel reported serving as a consultant to the National Football League and the Pritikin Longevity Center as well as acting as the national coordinator for the Sanofi-sponsored ODYSSEY Outcomes trial studying the PCSK9 inhibitor alirocumab (Praluent).

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – By far the most-important contributor to improved outcomes following out-of-hospital cardiac arrest during the past decade has been therapeutic hypothermia, Dr. N.A. Mark Estes III said at the Annual Cardiovascular Conference at Snowmass.

The No. 1 cause of in-hospital death in patients who arrive at the hospital with a perfusable rhythm following resuscitation from out-of-hospital cardiac arrest isn’t sepsis, hepatic or renal failure, or cardiogenic shock. It’s neurologic death caused by anoxic brain injury, which begins several hours after cardiac arrest and continues for about 48 hours. This is where therapeutic hypothermia has made a huge difference, said Dr. Estes, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

“One-half of out-of-hospital cardiac arrest survivors experience secondary anoxic brain damage of varying degrees. Until recently, there was no treatment with documented efficacy in preventing this damage. Despite multiple agents being looked at for neuroprevention, none really has worked. But therapeutic hypothermia has drastically improved outcomes. More than half of patients who arrive at the hospital with a perfusable rhythm and receive therapeutic hypothermia are discharged relatively neurologically intact. That’s a huge difference from what we used to see,” the electrophysiologist observed.

Indeed, the proportion of U.S. patients who experience out-of-hospital cardiac arrest and survive to hospital discharge neurologically intact is “dismal” at about 10%, he noted.

Virtually all specialized cardiac arrest centers now provide therapeutic hypothermia using various protocols. The demonstrated effectiveness of this postresuscitation therapy was an impetus for the American Heart Association policy statement calling for creation of regional cardiac resuscitation systems of care (Circulation. 2010 Feb 9;121[5]:709-29). To date, however, such organized systems exist in only a handful of states or portions of states.

Nonetheless, when an out-of-hospital cardiac arrest patient arrives at a community hospital that can’t provide emergency coronary angiography and therapeutic hypothermia, it’s appropriate to stabilize that patient in the emergency department and then transfer to a hospital that can, according to Dr. Estes.

The mechanism by which therapeutic hypothermia works has been well elucidated. The treatment curbs the process by which ischemia as a second blow triggers formation of oxygen free radicals, glutamate release, calcium shifts, and mitochondrial dysfunction, with resultant destruction of brain tissue.

Roughly 250,000 sudden cardiac deaths (SCDs) occur annually in this country. In addition to more widespread availability of therapeutic hypothermia and other forms of specialized postresuscitation care through creation of regional systems of care for out-of-hospital cardiac arrest, there are other opportunities for improving outcomes. These include earlier activation of the chain of survival that begins with a bystander dialing 911 as well as greater availability of public access defibrillation.

Dr. Estes emphasized that while these measures will further improve outcomes of cardiac arrest, they won’t actually reduce its frequency. By far the greatest opportunity in that realm lies in primordial prevention of coronary artery disease; that is, prevention of the risk factors for CAD. After all, he noted, 80% of all SCDs are associated with underlying ischemic heart disease. In 30% of SCDs, the fatal event is the first manifestation of previously unrecognized CAD. Another one-third of SCDs occur in patients with known CAD, but who weren’t considered at high risk for SCD because of their preserved left ventricular ejection fraction.

“There are a number of luminaries in the field who feel that if we’re really going to make an impact on sudden cardiac death, it’s going to be through primordial prevention of CAD,” the cardiologist said.

For this reason, he was thrilled to hear Dr. Robert A. Vogel elsewhere at the conference describe research by investigators at Affiris AG in Vienna who’ve created a peptide-based vaccine that inhibits PCSK9. Moreover, they showed it to be effective in sharply lowering LDL in mice (PLoS One. 2014 Dec 4;9[12]:e114469).

“I believe that in my lifetime, we will have an antiatherosclerotic vaccine that will lower LDL to an extent where this disease will not disappear but may get to a manageable extent, perhaps a 10% lifetime risk instead of the 55% lifetime risk of MI or stroke that we as Americans currently have,” predicted Dr. Vogel of the University of Colorado, Denver.

Dr. Vogel reported serving as a consultant to the National Football League and the Pritikin Longevity Center as well as acting as the national coordinator for the Sanofi-sponsored ODYSSEY Outcomes trial studying the PCSK9 inhibitor alirocumab (Praluent).

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – By far the most-important contributor to improved outcomes following out-of-hospital cardiac arrest during the past decade has been therapeutic hypothermia, Dr. N.A. Mark Estes III said at the Annual Cardiovascular Conference at Snowmass.

The No. 1 cause of in-hospital death in patients who arrive at the hospital with a perfusable rhythm following resuscitation from out-of-hospital cardiac arrest isn’t sepsis, hepatic or renal failure, or cardiogenic shock. It’s neurologic death caused by anoxic brain injury, which begins several hours after cardiac arrest and continues for about 48 hours. This is where therapeutic hypothermia has made a huge difference, said Dr. Estes, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

“One-half of out-of-hospital cardiac arrest survivors experience secondary anoxic brain damage of varying degrees. Until recently, there was no treatment with documented efficacy in preventing this damage. Despite multiple agents being looked at for neuroprevention, none really has worked. But therapeutic hypothermia has drastically improved outcomes. More than half of patients who arrive at the hospital with a perfusable rhythm and receive therapeutic hypothermia are discharged relatively neurologically intact. That’s a huge difference from what we used to see,” the electrophysiologist observed.

Indeed, the proportion of U.S. patients who experience out-of-hospital cardiac arrest and survive to hospital discharge neurologically intact is “dismal” at about 10%, he noted.

Virtually all specialized cardiac arrest centers now provide therapeutic hypothermia using various protocols. The demonstrated effectiveness of this postresuscitation therapy was an impetus for the American Heart Association policy statement calling for creation of regional cardiac resuscitation systems of care (Circulation. 2010 Feb 9;121[5]:709-29). To date, however, such organized systems exist in only a handful of states or portions of states.

Nonetheless, when an out-of-hospital cardiac arrest patient arrives at a community hospital that can’t provide emergency coronary angiography and therapeutic hypothermia, it’s appropriate to stabilize that patient in the emergency department and then transfer to a hospital that can, according to Dr. Estes.

The mechanism by which therapeutic hypothermia works has been well elucidated. The treatment curbs the process by which ischemia as a second blow triggers formation of oxygen free radicals, glutamate release, calcium shifts, and mitochondrial dysfunction, with resultant destruction of brain tissue.

Roughly 250,000 sudden cardiac deaths (SCDs) occur annually in this country. In addition to more widespread availability of therapeutic hypothermia and other forms of specialized postresuscitation care through creation of regional systems of care for out-of-hospital cardiac arrest, there are other opportunities for improving outcomes. These include earlier activation of the chain of survival that begins with a bystander dialing 911 as well as greater availability of public access defibrillation.

Dr. Estes emphasized that while these measures will further improve outcomes of cardiac arrest, they won’t actually reduce its frequency. By far the greatest opportunity in that realm lies in primordial prevention of coronary artery disease; that is, prevention of the risk factors for CAD. After all, he noted, 80% of all SCDs are associated with underlying ischemic heart disease. In 30% of SCDs, the fatal event is the first manifestation of previously unrecognized CAD. Another one-third of SCDs occur in patients with known CAD, but who weren’t considered at high risk for SCD because of their preserved left ventricular ejection fraction.

“There are a number of luminaries in the field who feel that if we’re really going to make an impact on sudden cardiac death, it’s going to be through primordial prevention of CAD,” the cardiologist said.

For this reason, he was thrilled to hear Dr. Robert A. Vogel elsewhere at the conference describe research by investigators at Affiris AG in Vienna who’ve created a peptide-based vaccine that inhibits PCSK9. Moreover, they showed it to be effective in sharply lowering LDL in mice (PLoS One. 2014 Dec 4;9[12]:e114469).

“I believe that in my lifetime, we will have an antiatherosclerotic vaccine that will lower LDL to an extent where this disease will not disappear but may get to a manageable extent, perhaps a 10% lifetime risk instead of the 55% lifetime risk of MI or stroke that we as Americans currently have,” predicted Dr. Vogel of the University of Colorado, Denver.

Dr. Vogel reported serving as a consultant to the National Football League and the Pritikin Longevity Center as well as acting as the national coordinator for the Sanofi-sponsored ODYSSEY Outcomes trial studying the PCSK9 inhibitor alirocumab (Praluent).

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

bjancin@frontlinemedcom.com