Cardiology

Children with congenital heart disease exposed to low-dose ionizing radiation from cardiac procedures had a cancer risk more than triple that of pediatric congenital heart disease (CHD) patients without such exposures, according to a large Canadian nested case-control study presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

This cancer risk was dose dependent. It rose stepwise with the number of cardiac procedures involving exposure to low-dose ionizing radiation (LDIR) and the total radiation dose. Moreover, roughly 80% of the cancers were of types known to be associated with radiation exposure in children, reported Elie Ganni, a medical student at McGill University, Montreal, working with MAUDE, the McGill Adult Unit for Congenital Heart Disease.

The MAUDE group previously published the first large, population-based study analyzing the association between LDIR from cardiac procedures and incident cancer in adults with CHD. The study, which included nearly 25,000 adult CHD patients aged 18-64 years with more than 250,000 person-years of follow-up, concluded that individuals with LDIR exposure from six or more cardiac procedures had a 140% greater cancer incidence than those with no or one exposure (Circulation. 2018 Mar 27;137[13]:1334-45).

Because children are considered to be more sensitive to the carcinogenic effects of LDIR than adults, the MAUDE group next did a similar study in a pediatric CHD population included in the Quebec Congenital Heart Disease Database. This nested case-control study included 232 children with CHD who were first diagnosed with cancer at a median age of 3.9 years and 8,160 pediatric CHD controls matched for gender and birth year. About 76% of cancers were diagnosed before age 7, 20% at ages 7-12 years, and the remaining 4% at ages 13-18. Hematologic malignancies accounted for 61% of the pediatric cancers, CNS cancers for another 12.5%, and thyroid cancers 6.6%; all three types of cancer are associated with radiation exposure.

After excluding all cardiac procedures involving LDIR performed within 6 months prior to cancer diagnosis, the risk of developing a pediatric cancer was 230% greater in children with LDIR exposure from cardiac procedures than in CHD patients without such exposure. For every 4 mSv in estimated LDIR exposure from cardiac procedures, the risk of cancer rose by 15.5%. In contrast, in the earlier study in adults with CHD, cancer risk climbed by 10% per 10 mSv. Patients with six or more LDIR cardiac procedures – not at all unusual in contemporary practice – were 2.4 times more likely to have cancer than those with no or one such radiation exposure.

Current ACC guidelines on radiation exposure from cardiac procedures recommend calculating an individual’s lifetime attributable cancer incidence and mortality risks, as well as adhering to the time-honored principle of ensuring that radiation exposure is as low as reasonably achievable without sacrificing quality of care.

“Our findings strongly support these ACC recommendations and moreover suggest that radiation surveillance for patients with congenital heart disease should be considered using radiation badges. Also, cancer surveillance guidelines should be considered for CHD patients exposed to LDIR,” Mr. Ganni said.

These suggestions for creation of patient radiation passports and cancer surveillance guidelines take on greater weight in light of two trends: the increasing life expectancy of children with CHD during the past 3 decades as a result of procedural advances that entail LDIR exposure, mostly for imaging, and the growing number of such procedures performed per patient earlier and earlier in life.

He and the MAUDE group plan to confirm their latest findings in other, larger data sets and hope to identify threshold effects for LDIR for specific cancers, with hematologic malignancies as the top priority.

Mr. Ganni reported having no financial conflicts regarding his study, funded by the Heart and Stroke Foundation of Canada, the Quebec Foundation for Health Research, and the Canadian Institutes for Health Research.

bjancin@mdedge.com

Children with congenital heart disease exposed to low-dose ionizing radiation from cardiac procedures had a cancer risk more than triple that of pediatric congenital heart disease (CHD) patients without such exposures, according to a large Canadian nested case-control study presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

This cancer risk was dose dependent. It rose stepwise with the number of cardiac procedures involving exposure to low-dose ionizing radiation (LDIR) and the total radiation dose. Moreover, roughly 80% of the cancers were of types known to be associated with radiation exposure in children, reported Elie Ganni, a medical student at McGill University, Montreal, working with MAUDE, the McGill Adult Unit for Congenital Heart Disease.

The MAUDE group previously published the first large, population-based study analyzing the association between LDIR from cardiac procedures and incident cancer in adults with CHD. The study, which included nearly 25,000 adult CHD patients aged 18-64 years with more than 250,000 person-years of follow-up, concluded that individuals with LDIR exposure from six or more cardiac procedures had a 140% greater cancer incidence than those with no or one exposure (Circulation. 2018 Mar 27;137[13]:1334-45).

Because children are considered to be more sensitive to the carcinogenic effects of LDIR than adults, the MAUDE group next did a similar study in a pediatric CHD population included in the Quebec Congenital Heart Disease Database. This nested case-control study included 232 children with CHD who were first diagnosed with cancer at a median age of 3.9 years and 8,160 pediatric CHD controls matched for gender and birth year. About 76% of cancers were diagnosed before age 7, 20% at ages 7-12 years, and the remaining 4% at ages 13-18. Hematologic malignancies accounted for 61% of the pediatric cancers, CNS cancers for another 12.5%, and thyroid cancers 6.6%; all three types of cancer are associated with radiation exposure.

After excluding all cardiac procedures involving LDIR performed within 6 months prior to cancer diagnosis, the risk of developing a pediatric cancer was 230% greater in children with LDIR exposure from cardiac procedures than in CHD patients without such exposure. For every 4 mSv in estimated LDIR exposure from cardiac procedures, the risk of cancer rose by 15.5%. In contrast, in the earlier study in adults with CHD, cancer risk climbed by 10% per 10 mSv. Patients with six or more LDIR cardiac procedures – not at all unusual in contemporary practice – were 2.4 times more likely to have cancer than those with no or one such radiation exposure.

Current ACC guidelines on radiation exposure from cardiac procedures recommend calculating an individual’s lifetime attributable cancer incidence and mortality risks, as well as adhering to the time-honored principle of ensuring that radiation exposure is as low as reasonably achievable without sacrificing quality of care.

“Our findings strongly support these ACC recommendations and moreover suggest that radiation surveillance for patients with congenital heart disease should be considered using radiation badges. Also, cancer surveillance guidelines should be considered for CHD patients exposed to LDIR,” Mr. Ganni said.

These suggestions for creation of patient radiation passports and cancer surveillance guidelines take on greater weight in light of two trends: the increasing life expectancy of children with CHD during the past 3 decades as a result of procedural advances that entail LDIR exposure, mostly for imaging, and the growing number of such procedures performed per patient earlier and earlier in life.

He and the MAUDE group plan to confirm their latest findings in other, larger data sets and hope to identify threshold effects for LDIR for specific cancers, with hematologic malignancies as the top priority.

Mr. Ganni reported having no financial conflicts regarding his study, funded by the Heart and Stroke Foundation of Canada, the Quebec Foundation for Health Research, and the Canadian Institutes for Health Research.

bjancin@mdedge.com

Children with congenital heart disease exposed to low-dose ionizing radiation from cardiac procedures had a cancer risk more than triple that of pediatric congenital heart disease (CHD) patients without such exposures, according to a large Canadian nested case-control study presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

This cancer risk was dose dependent. It rose stepwise with the number of cardiac procedures involving exposure to low-dose ionizing radiation (LDIR) and the total radiation dose. Moreover, roughly 80% of the cancers were of types known to be associated with radiation exposure in children, reported Elie Ganni, a medical student at McGill University, Montreal, working with MAUDE, the McGill Adult Unit for Congenital Heart Disease.

The MAUDE group previously published the first large, population-based study analyzing the association between LDIR from cardiac procedures and incident cancer in adults with CHD. The study, which included nearly 25,000 adult CHD patients aged 18-64 years with more than 250,000 person-years of follow-up, concluded that individuals with LDIR exposure from six or more cardiac procedures had a 140% greater cancer incidence than those with no or one exposure (Circulation. 2018 Mar 27;137[13]:1334-45).

Because children are considered to be more sensitive to the carcinogenic effects of LDIR than adults, the MAUDE group next did a similar study in a pediatric CHD population included in the Quebec Congenital Heart Disease Database. This nested case-control study included 232 children with CHD who were first diagnosed with cancer at a median age of 3.9 years and 8,160 pediatric CHD controls matched for gender and birth year. About 76% of cancers were diagnosed before age 7, 20% at ages 7-12 years, and the remaining 4% at ages 13-18. Hematologic malignancies accounted for 61% of the pediatric cancers, CNS cancers for another 12.5%, and thyroid cancers 6.6%; all three types of cancer are associated with radiation exposure.

After excluding all cardiac procedures involving LDIR performed within 6 months prior to cancer diagnosis, the risk of developing a pediatric cancer was 230% greater in children with LDIR exposure from cardiac procedures than in CHD patients without such exposure. For every 4 mSv in estimated LDIR exposure from cardiac procedures, the risk of cancer rose by 15.5%. In contrast, in the earlier study in adults with CHD, cancer risk climbed by 10% per 10 mSv. Patients with six or more LDIR cardiac procedures – not at all unusual in contemporary practice – were 2.4 times more likely to have cancer than those with no or one such radiation exposure.

Current ACC guidelines on radiation exposure from cardiac procedures recommend calculating an individual’s lifetime attributable cancer incidence and mortality risks, as well as adhering to the time-honored principle of ensuring that radiation exposure is as low as reasonably achievable without sacrificing quality of care.

“Our findings strongly support these ACC recommendations and moreover suggest that radiation surveillance for patients with congenital heart disease should be considered using radiation badges. Also, cancer surveillance guidelines should be considered for CHD patients exposed to LDIR,” Mr. Ganni said.

These suggestions for creation of patient radiation passports and cancer surveillance guidelines take on greater weight in light of two trends: the increasing life expectancy of children with CHD during the past 3 decades as a result of procedural advances that entail LDIR exposure, mostly for imaging, and the growing number of such procedures performed per patient earlier and earlier in life.

He and the MAUDE group plan to confirm their latest findings in other, larger data sets and hope to identify threshold effects for LDIR for specific cancers, with hematologic malignancies as the top priority.

Mr. Ganni reported having no financial conflicts regarding his study, funded by the Heart and Stroke Foundation of Canada, the Quebec Foundation for Health Research, and the Canadian Institutes for Health Research.

bjancin@mdedge.com

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

mzoler@mdedge.com

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

mzoler@mdedge.com

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

mzoler@mdedge.com

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A novel telemedicine approach to remotely guide ST-segment elevation myocardial infarction treatment in four Latin American countries screened more than 780,000 patients and resulted in a mortality rate of 5.2%, results from a 1-year, prospective, observational study showed.

“We have created a modality where the care of acute MI can be remotely guided,” lead investigator Sameer Mehta, MD, MBA, said during a press briefing at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “This flattens the disparity between the developed and the developing countries, particularly in the poorer parts of Africa, the Middle East, and Southeast Asia.”

Dr. Mehta, chairman of the Lumen Foundation in Miami, and colleagues developed a “hub and spoke” platform to expand STEMI access to more than 100 million people in Brazil, Colombia, Mexico, and Argentina. For the effort, known as the Latin America Telemedicine Infarct Network (LATIN), “spokes” consisted of small clinics and primary health care centers in remote locations, while the “hubs” were medical centers that provided percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. There were 313 spokes, 47 hubs, and more than 2,000 health care professionals who participated in the endeavor, including about 600 physicians.

The study, which is the largest of its kind, implemented a 3T strategy: telemedicine, triage, and transport, “which was the hardest part,” Dr. Mehta said. “In some cases, the spokes were located up to 300 miles away from the hubs. Up to 11% of these spokes in the remote areas did not even have a physician. Some had nurses who were triaging the patients.”

Patients who presented at spoke sites were enrolled into LATIN and data were collected through a form that included patient demographics, previous medical history, and an ECG. This information was sent through an app to one of three telemedicine diagnosis centers with 24/7 access to a cardiologist: one in Colombia, one in Brazil, one in Argentina. Once STEMI was identified by ECG, the STEMI protocol was activated, sending alerts to both designated hub and spoke sites and triggering ambulance dispatch. At the spoke sites, thrombolysis, a pharmaco-invasive strategy, or a primary PCI was performed, depending on case and treatment availability. Patients with successful thrombolysis were stabilized for up to 24 hours before transferral to a hub. Patients for whom reperfusion failed were transferred immediately to a hub for rescue PCI.

Dr. Mehta reported findings from 780,234 telemedicine encounters that occurred in the LATIN network in 2018. Telemedicine experts diagnosed 8,395 patients (1%) with STEMI, of which 3,872 (46%) were urgently treated at 47 hubs. A total of 3,015 (78%) were reperfused with PCI. Time-to-telemedicine diagnosis averaged 3.5 minutes. “It used to take us 11 minutes of time to make a diagnosis by telemedicine,” Dr. Mehta said. “By the time we were done with the trial, the time to diagnosis was brought down to 3.5 minutes.” Average door-to-balloon time was 48 minutes and the STEMI mortality was 5.2%. This represents a 55% reduction in STEMI mortality from when LATIN began as a pilot project in 2013, Dr. Mehta said.

Hypertension was the most prevalent underlying disease (59%), followed by smoking (30%) and diabetes (29%), and the male to female STEMI diagnosis ratio was 1.71. The chief reason for nontreatment was coverage denial from insurance carriers (71%). “Getting payers onboard is extremely difficult, because being located here in Miami, is it very hard for me to convince them about the importance of supporting these people,” Dr. Mehta said. “However, as time has passed [and with] coverage of LATIN by the media, the program has become better known. We have been able to work mainly through the health secretaries [in these four countries], but is difficult from there onward.”

LATIN investigators faced other hurdles, which were unique in each of the four countries. “In Colombia, we were facing all sorts of geographical challenges; Brazil was challenging because of its size of the country and [difficulty establishing relationships with] some of the inner-city hospitals,” he said. “Mexico and Argentina were unique from the telemedicine point of view.” The fact that the care of LATIN patients was navigated from one of three telemedicine diagnosis centers “demonstrates the ability of telemedicine,” he said. “If I am able to guide a patient in Mexico from Bogotá, Colombia, it should be easy to guide a patient from Miami who’s presenting in Zambia.”

Dealing with the lack of ambulance services in Brazil, Colombia, Mexico, and Argentina has also been a hitch to the effort. “There is either a complete lack of ambulances or there is no central ambulance system,” he said. “In one of the earlier cities where we started the program in Colombia, 84% of patients used to self-transport. At the moment, 79% are being transported by ambulance. So, the halo effect of how LATIN has helped MI management has been impressive.”

Despite the lack of a comparator study as robust as LATIN, the program was estimated to reach between $39.6 million and $119 million USD total savings during the study period. This includes the cost of tele-emergency encounters, avoided transfers, and the cost of transportation. The investigators project that by the year 2026, 5 million patients could be triaged by this telemedicine pathway, saving $249 million. “As we are getting excited about the developments and the possibilities of telemedicine in the COVID-19 era, I think the work of LATIN becomes all the more relevant,” Dr. Mehta said during his main presentation.

During the press briefing, Timothy D. Henry, MD, praised the success of LATIN in reaching an underserved population. “The majority of these patients 10 years ago were not being treated with any reperfusion therapy at all,” said Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati. “With rapid diagnosis and the process of putting [LATIN] in place, that has increased to the point where 78% are now getting primary PCI. That is remarkable.”

dbrunk@mdedge.com

A novel telemedicine approach to remotely guide ST-segment elevation myocardial infarction treatment in four Latin American countries screened more than 780,000 patients and resulted in a mortality rate of 5.2%, results from a 1-year, prospective, observational study showed.

“We have created a modality where the care of acute MI can be remotely guided,” lead investigator Sameer Mehta, MD, MBA, said during a press briefing at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “This flattens the disparity between the developed and the developing countries, particularly in the poorer parts of Africa, the Middle East, and Southeast Asia.”

Dr. Mehta, chairman of the Lumen Foundation in Miami, and colleagues developed a “hub and spoke” platform to expand STEMI access to more than 100 million people in Brazil, Colombia, Mexico, and Argentina. For the effort, known as the Latin America Telemedicine Infarct Network (LATIN), “spokes” consisted of small clinics and primary health care centers in remote locations, while the “hubs” were medical centers that provided percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. There were 313 spokes, 47 hubs, and more than 2,000 health care professionals who participated in the endeavor, including about 600 physicians.

The study, which is the largest of its kind, implemented a 3T strategy: telemedicine, triage, and transport, “which was the hardest part,” Dr. Mehta said. “In some cases, the spokes were located up to 300 miles away from the hubs. Up to 11% of these spokes in the remote areas did not even have a physician. Some had nurses who were triaging the patients.”

Patients who presented at spoke sites were enrolled into LATIN and data were collected through a form that included patient demographics, previous medical history, and an ECG. This information was sent through an app to one of three telemedicine diagnosis centers with 24/7 access to a cardiologist: one in Colombia, one in Brazil, one in Argentina. Once STEMI was identified by ECG, the STEMI protocol was activated, sending alerts to both designated hub and spoke sites and triggering ambulance dispatch. At the spoke sites, thrombolysis, a pharmaco-invasive strategy, or a primary PCI was performed, depending on case and treatment availability. Patients with successful thrombolysis were stabilized for up to 24 hours before transferral to a hub. Patients for whom reperfusion failed were transferred immediately to a hub for rescue PCI.

Dr. Mehta reported findings from 780,234 telemedicine encounters that occurred in the LATIN network in 2018. Telemedicine experts diagnosed 8,395 patients (1%) with STEMI, of which 3,872 (46%) were urgently treated at 47 hubs. A total of 3,015 (78%) were reperfused with PCI. Time-to-telemedicine diagnosis averaged 3.5 minutes. “It used to take us 11 minutes of time to make a diagnosis by telemedicine,” Dr. Mehta said. “By the time we were done with the trial, the time to diagnosis was brought down to 3.5 minutes.” Average door-to-balloon time was 48 minutes and the STEMI mortality was 5.2%. This represents a 55% reduction in STEMI mortality from when LATIN began as a pilot project in 2013, Dr. Mehta said.

Hypertension was the most prevalent underlying disease (59%), followed by smoking (30%) and diabetes (29%), and the male to female STEMI diagnosis ratio was 1.71. The chief reason for nontreatment was coverage denial from insurance carriers (71%). “Getting payers onboard is extremely difficult, because being located here in Miami, is it very hard for me to convince them about the importance of supporting these people,” Dr. Mehta said. “However, as time has passed [and with] coverage of LATIN by the media, the program has become better known. We have been able to work mainly through the health secretaries [in these four countries], but is difficult from there onward.”

LATIN investigators faced other hurdles, which were unique in each of the four countries. “In Colombia, we were facing all sorts of geographical challenges; Brazil was challenging because of its size of the country and [difficulty establishing relationships with] some of the inner-city hospitals,” he said. “Mexico and Argentina were unique from the telemedicine point of view.” The fact that the care of LATIN patients was navigated from one of three telemedicine diagnosis centers “demonstrates the ability of telemedicine,” he said. “If I am able to guide a patient in Mexico from Bogotá, Colombia, it should be easy to guide a patient from Miami who’s presenting in Zambia.”

Dealing with the lack of ambulance services in Brazil, Colombia, Mexico, and Argentina has also been a hitch to the effort. “There is either a complete lack of ambulances or there is no central ambulance system,” he said. “In one of the earlier cities where we started the program in Colombia, 84% of patients used to self-transport. At the moment, 79% are being transported by ambulance. So, the halo effect of how LATIN has helped MI management has been impressive.”

Despite the lack of a comparator study as robust as LATIN, the program was estimated to reach between $39.6 million and $119 million USD total savings during the study period. This includes the cost of tele-emergency encounters, avoided transfers, and the cost of transportation. The investigators project that by the year 2026, 5 million patients could be triaged by this telemedicine pathway, saving $249 million. “As we are getting excited about the developments and the possibilities of telemedicine in the COVID-19 era, I think the work of LATIN becomes all the more relevant,” Dr. Mehta said during his main presentation.

During the press briefing, Timothy D. Henry, MD, praised the success of LATIN in reaching an underserved population. “The majority of these patients 10 years ago were not being treated with any reperfusion therapy at all,” said Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati. “With rapid diagnosis and the process of putting [LATIN] in place, that has increased to the point where 78% are now getting primary PCI. That is remarkable.”

dbrunk@mdedge.com

A novel telemedicine approach to remotely guide ST-segment elevation myocardial infarction treatment in four Latin American countries screened more than 780,000 patients and resulted in a mortality rate of 5.2%, results from a 1-year, prospective, observational study showed.

“We have created a modality where the care of acute MI can be remotely guided,” lead investigator Sameer Mehta, MD, MBA, said during a press briefing at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “This flattens the disparity between the developed and the developing countries, particularly in the poorer parts of Africa, the Middle East, and Southeast Asia.”

Dr. Mehta, chairman of the Lumen Foundation in Miami, and colleagues developed a “hub and spoke” platform to expand STEMI access to more than 100 million people in Brazil, Colombia, Mexico, and Argentina. For the effort, known as the Latin America Telemedicine Infarct Network (LATIN), “spokes” consisted of small clinics and primary health care centers in remote locations, while the “hubs” were medical centers that provided percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. There were 313 spokes, 47 hubs, and more than 2,000 health care professionals who participated in the endeavor, including about 600 physicians.

The study, which is the largest of its kind, implemented a 3T strategy: telemedicine, triage, and transport, “which was the hardest part,” Dr. Mehta said. “In some cases, the spokes were located up to 300 miles away from the hubs. Up to 11% of these spokes in the remote areas did not even have a physician. Some had nurses who were triaging the patients.”

Patients who presented at spoke sites were enrolled into LATIN and data were collected through a form that included patient demographics, previous medical history, and an ECG. This information was sent through an app to one of three telemedicine diagnosis centers with 24/7 access to a cardiologist: one in Colombia, one in Brazil, one in Argentina. Once STEMI was identified by ECG, the STEMI protocol was activated, sending alerts to both designated hub and spoke sites and triggering ambulance dispatch. At the spoke sites, thrombolysis, a pharmaco-invasive strategy, or a primary PCI was performed, depending on case and treatment availability. Patients with successful thrombolysis were stabilized for up to 24 hours before transferral to a hub. Patients for whom reperfusion failed were transferred immediately to a hub for rescue PCI.

Dr. Mehta reported findings from 780,234 telemedicine encounters that occurred in the LATIN network in 2018. Telemedicine experts diagnosed 8,395 patients (1%) with STEMI, of which 3,872 (46%) were urgently treated at 47 hubs. A total of 3,015 (78%) were reperfused with PCI. Time-to-telemedicine diagnosis averaged 3.5 minutes. “It used to take us 11 minutes of time to make a diagnosis by telemedicine,” Dr. Mehta said. “By the time we were done with the trial, the time to diagnosis was brought down to 3.5 minutes.” Average door-to-balloon time was 48 minutes and the STEMI mortality was 5.2%. This represents a 55% reduction in STEMI mortality from when LATIN began as a pilot project in 2013, Dr. Mehta said.

Hypertension was the most prevalent underlying disease (59%), followed by smoking (30%) and diabetes (29%), and the male to female STEMI diagnosis ratio was 1.71. The chief reason for nontreatment was coverage denial from insurance carriers (71%). “Getting payers onboard is extremely difficult, because being located here in Miami, is it very hard for me to convince them about the importance of supporting these people,” Dr. Mehta said. “However, as time has passed [and with] coverage of LATIN by the media, the program has become better known. We have been able to work mainly through the health secretaries [in these four countries], but is difficult from there onward.”

LATIN investigators faced other hurdles, which were unique in each of the four countries. “In Colombia, we were facing all sorts of geographical challenges; Brazil was challenging because of its size of the country and [difficulty establishing relationships with] some of the inner-city hospitals,” he said. “Mexico and Argentina were unique from the telemedicine point of view.” The fact that the care of LATIN patients was navigated from one of three telemedicine diagnosis centers “demonstrates the ability of telemedicine,” he said. “If I am able to guide a patient in Mexico from Bogotá, Colombia, it should be easy to guide a patient from Miami who’s presenting in Zambia.”

Dealing with the lack of ambulance services in Brazil, Colombia, Mexico, and Argentina has also been a hitch to the effort. “There is either a complete lack of ambulances or there is no central ambulance system,” he said. “In one of the earlier cities where we started the program in Colombia, 84% of patients used to self-transport. At the moment, 79% are being transported by ambulance. So, the halo effect of how LATIN has helped MI management has been impressive.”

Despite the lack of a comparator study as robust as LATIN, the program was estimated to reach between $39.6 million and $119 million USD total savings during the study period. This includes the cost of tele-emergency encounters, avoided transfers, and the cost of transportation. The investigators project that by the year 2026, 5 million patients could be triaged by this telemedicine pathway, saving $249 million. “As we are getting excited about the developments and the possibilities of telemedicine in the COVID-19 era, I think the work of LATIN becomes all the more relevant,” Dr. Mehta said during his main presentation.

During the press briefing, Timothy D. Henry, MD, praised the success of LATIN in reaching an underserved population. “The majority of these patients 10 years ago were not being treated with any reperfusion therapy at all,” said Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati. “With rapid diagnosis and the process of putting [LATIN] in place, that has increased to the point where 78% are now getting primary PCI. That is remarkable.”

dbrunk@mdedge.com

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

A polygenic risk score based on analysis of 29 discrete genetic variants linked with abdominal aortic aneurysms appeared better than the current criteria that clinicians use to identify people to screen for this disorder, potentially paving the way for more efficient use of screening resources.

Ryuji Suzuki

Future screening guidelines for abdominal aortic aneurysms (AAA) “should consider including individuals with high polygenic risk for screening ultrasonography,” Derek Klarin, MD, said at the virtual Vascular Discovery Scientific Sessions 2020, organized by the American Heart Association.

The data he reported showed that when researchers applied the polygenic risk score (PRS) to men aged older than 50 years in three independent validation cohorts of people with primarily European ancestry, those with scores in the top 5 percentile within each cohort had a collective AAA prevalence rate of 8.6% (95% CI 7.3%-9.8%).

This 8.6% pick-up rate using the PRS to help identify screening candidates for this male demographic subgroup compared favorably with previously reported prevalence rates of AAA detected by ultrasonography (defined as aneurysms of at least 3.0 cm in diameter) in men aged 65 years or older with a history of ever smoking. Last year, the U.S. Preventive Services Task Force issued an updated recommendation to perform a one-time ultrasound screening of 65- to 75-year-old men who ever smoked and cited five reported screening studies that found prevalence rates in these people of 3.3%-7.6% (JAMA. 2019 Dec 10;322[22]:2211-8). An earlier review of the topic by the task force cited an average estimated prevalence of 6%-7% in men at least 65 years old and with a smoking history (Ann Intern Med. 2014 Aug 19;161[4]: 281-90).

“You can use [the PRS] with other risk factors to increase the yield of identifying those at high risk,” Dr. Klarin said during a discussion of his report. He noted the possibility of using it to identify people at-risk early on, at birth, “prior to other risk factors being present,” as well as using the PRS as an add-on to known risk factors when assessing adults. He stressed that validations he has run so far still leave the PRS a step away from routine use, although it is “quite close,” said Dr. Klarin, a vascular surgeon at the University of Florida in Gainesville.

For use in routine practice, the PRS needs “further validation,” including further assessment of its performance in other age groups, in a wider range of ethnic groups, and in women, said Chris Semsarian, MBBS, professor of medicine at the University of Sydney and head of the Molecular Cardiology Program at its Centenary Institute. However, Dr. Semsarian also said that he saw great promise for the potential of the PRS, and its development so far had been solid.

“The study was meticulously undertaken, with a large number of AAA cases and controls. Both the derivation and validation are robust. There is great potential to use such a genetic risk score in the clinical setting, along with other risk factors such as smoking, high blood pressure, and lipid levels. The PRS adds another piece in the puzzle of risk of AAA by adding in genetic or inherited risk. An additional 1%-2% in pick-up rate would still lead to many thousands more AAA detected and lives saved. The PRS doesn’t replace environmental factors that contribute to AAA risk but adds a genetic component” when estimating a person’s overall risk and the appropriateness of screening ultrasound, Dr. Semsarian said in an interview.

The derivation analysis that Dr. Klarin and associates ran used data from the Million Veteran Program that included 7,642 people with AAA and matched them with more than 172,000 controls from the same database. This generated three alternative PRSs that involved testing for 29, 301, or 3,699 different mutations or polymorphisms that discriminated cases from controls. They compared these three scoring formulas in 1,000 AAA cases and 7,700 matched controls from the Mayo Clinic’s patient database, which showed that the 29-item PRS performed best, boosting identification of cases with a statistically significant odds ratio of 1.26.

They then ran the 29-item PRS in four additional large data banks, three that included mostly people of European ancestry and one that included mostly people with an African heritage. In the three data banks with people of mostly European background, the 29-item PRS performed even better than it did using the Mayo Clinic data, but this PRS was less informative in people with African ancestry. The analyses also suggested that the PRS identified elevated AAA risk independently of information on a family history of AAA, Dr. Klarin said.

The study had no commercial funding. Dr. Klarin has been a consultant to Regeneron.

mzoler@mdedge.com

SOURCE: Klarin D et al. Vascular Discovery 2020, abstract 170.

A polygenic risk score based on analysis of 29 discrete genetic variants linked with abdominal aortic aneurysms appeared better than the current criteria that clinicians use to identify people to screen for this disorder, potentially paving the way for more efficient use of screening resources.

Ryuji Suzuki

Future screening guidelines for abdominal aortic aneurysms (AAA) “should consider including individuals with high polygenic risk for screening ultrasonography,” Derek Klarin, MD, said at the virtual Vascular Discovery Scientific Sessions 2020, organized by the American Heart Association.

The data he reported showed that when researchers applied the polygenic risk score (PRS) to men aged older than 50 years in three independent validation cohorts of people with primarily European ancestry, those with scores in the top 5 percentile within each cohort had a collective AAA prevalence rate of 8.6% (95% CI 7.3%-9.8%).

This 8.6% pick-up rate using the PRS to help identify screening candidates for this male demographic subgroup compared favorably with previously reported prevalence rates of AAA detected by ultrasonography (defined as aneurysms of at least 3.0 cm in diameter) in men aged 65 years or older with a history of ever smoking. Last year, the U.S. Preventive Services Task Force issued an updated recommendation to perform a one-time ultrasound screening of 65- to 75-year-old men who ever smoked and cited five reported screening studies that found prevalence rates in these people of 3.3%-7.6% (JAMA. 2019 Dec 10;322[22]:2211-8). An earlier review of the topic by the task force cited an average estimated prevalence of 6%-7% in men at least 65 years old and with a smoking history (Ann Intern Med. 2014 Aug 19;161[4]: 281-90).

“You can use [the PRS] with other risk factors to increase the yield of identifying those at high risk,” Dr. Klarin said during a discussion of his report. He noted the possibility of using it to identify people at-risk early on, at birth, “prior to other risk factors being present,” as well as using the PRS as an add-on to known risk factors when assessing adults. He stressed that validations he has run so far still leave the PRS a step away from routine use, although it is “quite close,” said Dr. Klarin, a vascular surgeon at the University of Florida in Gainesville.

For use in routine practice, the PRS needs “further validation,” including further assessment of its performance in other age groups, in a wider range of ethnic groups, and in women, said Chris Semsarian, MBBS, professor of medicine at the University of Sydney and head of the Molecular Cardiology Program at its Centenary Institute. However, Dr. Semsarian also said that he saw great promise for the potential of the PRS, and its development so far had been solid.

“The study was meticulously undertaken, with a large number of AAA cases and controls. Both the derivation and validation are robust. There is great potential to use such a genetic risk score in the clinical setting, along with other risk factors such as smoking, high blood pressure, and lipid levels. The PRS adds another piece in the puzzle of risk of AAA by adding in genetic or inherited risk. An additional 1%-2% in pick-up rate would still lead to many thousands more AAA detected and lives saved. The PRS doesn’t replace environmental factors that contribute to AAA risk but adds a genetic component” when estimating a person’s overall risk and the appropriateness of screening ultrasound, Dr. Semsarian said in an interview.

The derivation analysis that Dr. Klarin and associates ran used data from the Million Veteran Program that included 7,642 people with AAA and matched them with more than 172,000 controls from the same database. This generated three alternative PRSs that involved testing for 29, 301, or 3,699 different mutations or polymorphisms that discriminated cases from controls. They compared these three scoring formulas in 1,000 AAA cases and 7,700 matched controls from the Mayo Clinic’s patient database, which showed that the 29-item PRS performed best, boosting identification of cases with a statistically significant odds ratio of 1.26.

They then ran the 29-item PRS in four additional large data banks, three that included mostly people of European ancestry and one that included mostly people with an African heritage. In the three data banks with people of mostly European background, the 29-item PRS performed even better than it did using the Mayo Clinic data, but this PRS was less informative in people with African ancestry. The analyses also suggested that the PRS identified elevated AAA risk independently of information on a family history of AAA, Dr. Klarin said.

The study had no commercial funding. Dr. Klarin has been a consultant to Regeneron.

mzoler@mdedge.com

SOURCE: Klarin D et al. Vascular Discovery 2020, abstract 170.

A polygenic risk score based on analysis of 29 discrete genetic variants linked with abdominal aortic aneurysms appeared better than the current criteria that clinicians use to identify people to screen for this disorder, potentially paving the way for more efficient use of screening resources.

Ryuji Suzuki

Future screening guidelines for abdominal aortic aneurysms (AAA) “should consider including individuals with high polygenic risk for screening ultrasonography,” Derek Klarin, MD, said at the virtual Vascular Discovery Scientific Sessions 2020, organized by the American Heart Association.

The data he reported showed that when researchers applied the polygenic risk score (PRS) to men aged older than 50 years in three independent validation cohorts of people with primarily European ancestry, those with scores in the top 5 percentile within each cohort had a collective AAA prevalence rate of 8.6% (95% CI 7.3%-9.8%).

This 8.6% pick-up rate using the PRS to help identify screening candidates for this male demographic subgroup compared favorably with previously reported prevalence rates of AAA detected by ultrasonography (defined as aneurysms of at least 3.0 cm in diameter) in men aged 65 years or older with a history of ever smoking. Last year, the U.S. Preventive Services Task Force issued an updated recommendation to perform a one-time ultrasound screening of 65- to 75-year-old men who ever smoked and cited five reported screening studies that found prevalence rates in these people of 3.3%-7.6% (JAMA. 2019 Dec 10;322[22]:2211-8). An earlier review of the topic by the task force cited an average estimated prevalence of 6%-7% in men at least 65 years old and with a smoking history (Ann Intern Med. 2014 Aug 19;161[4]: 281-90).

“You can use [the PRS] with other risk factors to increase the yield of identifying those at high risk,” Dr. Klarin said during a discussion of his report. He noted the possibility of using it to identify people at-risk early on, at birth, “prior to other risk factors being present,” as well as using the PRS as an add-on to known risk factors when assessing adults. He stressed that validations he has run so far still leave the PRS a step away from routine use, although it is “quite close,” said Dr. Klarin, a vascular surgeon at the University of Florida in Gainesville.

For use in routine practice, the PRS needs “further validation,” including further assessment of its performance in other age groups, in a wider range of ethnic groups, and in women, said Chris Semsarian, MBBS, professor of medicine at the University of Sydney and head of the Molecular Cardiology Program at its Centenary Institute. However, Dr. Semsarian also said that he saw great promise for the potential of the PRS, and its development so far had been solid.

“The study was meticulously undertaken, with a large number of AAA cases and controls. Both the derivation and validation are robust. There is great potential to use such a genetic risk score in the clinical setting, along with other risk factors such as smoking, high blood pressure, and lipid levels. The PRS adds another piece in the puzzle of risk of AAA by adding in genetic or inherited risk. An additional 1%-2% in pick-up rate would still lead to many thousands more AAA detected and lives saved. The PRS doesn’t replace environmental factors that contribute to AAA risk but adds a genetic component” when estimating a person’s overall risk and the appropriateness of screening ultrasound, Dr. Semsarian said in an interview.

The derivation analysis that Dr. Klarin and associates ran used data from the Million Veteran Program that included 7,642 people with AAA and matched them with more than 172,000 controls from the same database. This generated three alternative PRSs that involved testing for 29, 301, or 3,699 different mutations or polymorphisms that discriminated cases from controls. They compared these three scoring formulas in 1,000 AAA cases and 7,700 matched controls from the Mayo Clinic’s patient database, which showed that the 29-item PRS performed best, boosting identification of cases with a statistically significant odds ratio of 1.26.

They then ran the 29-item PRS in four additional large data banks, three that included mostly people of European ancestry and one that included mostly people with an African heritage. In the three data banks with people of mostly European background, the 29-item PRS performed even better than it did using the Mayo Clinic data, but this PRS was less informative in people with African ancestry. The analyses also suggested that the PRS identified elevated AAA risk independently of information on a family history of AAA, Dr. Klarin said.

The study had no commercial funding. Dr. Klarin has been a consultant to Regeneron.

mzoler@mdedge.com

SOURCE: Klarin D et al. Vascular Discovery 2020, abstract 170.

Patients with obstructive hypertrophic cardiomyopathy (HCM) who took an investigational agent that targets cardiac myosin over about 7 months showed across-the-board improvements in functional capacity, symptoms, and left ventricular outflow obstruction in a randomized, controlled trial.

Treatment with the oral drug mavacamten (or MYK-461) was well tolerated and showed no untoward safety issues, compared with placebo in the phase 3 EXPLORER-HCM trial, its developer, MyoKardia, announced in a press release. The top-line trial results were made public in advance of a more expansive presentation at a later date.

The company describes mavacamten as an allosteric modulator of cardiac myosin that “reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.”

In the EXPLORER-HCM trial, with its 251 patients with symptomatic obstructive HCM, 37% of those randomly assigned to receive once-daily mavacamten and 17% of those given placebo (P =.0005) reached the functional primary endpoint by 30 weeks, the company reported.

The primary endpoint was a composite of either a ≥1.5 mL/kg per min improvement in peak VO2 along with symptomatic improvement or ≥3.0 mL/kg per min improvement without deterioration of symptom status.

Patients taking mavacamten also showed significant improvement in the secondary endpoints of left ventricular outflow tract peak gradient after exercise, NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and HCM Symptom Questionnaire Shortness of Breath Domain score, all at P = .0001, and peak VO₂ at P = .0006, MyoKardia reported.

The company said beyond its bid to have the drug approved for obstructive HCM, based on its mechanism of action it foresees the drug as a potential treatment for nonobstructive HCM and for some patients with heart failure with preserved ejection fraction.

This article first appeared on Medscape.com.

Patients with obstructive hypertrophic cardiomyopathy (HCM) who took an investigational agent that targets cardiac myosin over about 7 months showed across-the-board improvements in functional capacity, symptoms, and left ventricular outflow obstruction in a randomized, controlled trial.

Treatment with the oral drug mavacamten (or MYK-461) was well tolerated and showed no untoward safety issues, compared with placebo in the phase 3 EXPLORER-HCM trial, its developer, MyoKardia, announced in a press release. The top-line trial results were made public in advance of a more expansive presentation at a later date.

The company describes mavacamten as an allosteric modulator of cardiac myosin that “reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.”

In the EXPLORER-HCM trial, with its 251 patients with symptomatic obstructive HCM, 37% of those randomly assigned to receive once-daily mavacamten and 17% of those given placebo (P =.0005) reached the functional primary endpoint by 30 weeks, the company reported.

The primary endpoint was a composite of either a ≥1.5 mL/kg per min improvement in peak VO2 along with symptomatic improvement or ≥3.0 mL/kg per min improvement without deterioration of symptom status.

Patients taking mavacamten also showed significant improvement in the secondary endpoints of left ventricular outflow tract peak gradient after exercise, NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and HCM Symptom Questionnaire Shortness of Breath Domain score, all at P = .0001, and peak VO₂ at P = .0006, MyoKardia reported.

The company said beyond its bid to have the drug approved for obstructive HCM, based on its mechanism of action it foresees the drug as a potential treatment for nonobstructive HCM and for some patients with heart failure with preserved ejection fraction.

This article first appeared on Medscape.com.

Patients with obstructive hypertrophic cardiomyopathy (HCM) who took an investigational agent that targets cardiac myosin over about 7 months showed across-the-board improvements in functional capacity, symptoms, and left ventricular outflow obstruction in a randomized, controlled trial.

Treatment with the oral drug mavacamten (or MYK-461) was well tolerated and showed no untoward safety issues, compared with placebo in the phase 3 EXPLORER-HCM trial, its developer, MyoKardia, announced in a press release. The top-line trial results were made public in advance of a more expansive presentation at a later date.

The company describes mavacamten as an allosteric modulator of cardiac myosin that “reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.”

In the EXPLORER-HCM trial, with its 251 patients with symptomatic obstructive HCM, 37% of those randomly assigned to receive once-daily mavacamten and 17% of those given placebo (P =.0005) reached the functional primary endpoint by 30 weeks, the company reported.

The primary endpoint was a composite of either a ≥1.5 mL/kg per min improvement in peak VO2 along with symptomatic improvement or ≥3.0 mL/kg per min improvement without deterioration of symptom status.

Patients taking mavacamten also showed significant improvement in the secondary endpoints of left ventricular outflow tract peak gradient after exercise, NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and HCM Symptom Questionnaire Shortness of Breath Domain score, all at P = .0001, and peak VO₂ at P = .0006, MyoKardia reported.

The company said beyond its bid to have the drug approved for obstructive HCM, based on its mechanism of action it foresees the drug as a potential treatment for nonobstructive HCM and for some patients with heart failure with preserved ejection fraction.

This article first appeared on Medscape.com.

Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.

“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.

“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.

In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.

Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.

“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.

In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.

Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.

mzoler@mdedge.com

Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.

“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.

“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.

In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.

Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.

“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.

In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.

Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.

mzoler@mdedge.com

Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.

“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.

“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.

In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.

Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.

“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.

In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.

Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.

mzoler@mdedge.com

The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet.

“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.

The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.

But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.

The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”

“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m²,” he added. “The relationship was pretty tight, pretty quick.”

“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.

Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.

“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.

“We should think of them as a susceptible population.”

Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.

“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
 

Trio of mechanisms explain obesity’s extra COVID-19 risks

Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.

When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.

Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.

The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.

Median BMI among study participants was 29.3 kg/m², with only a quarter having a BMI lower than 26 kg/m² and another 25% having a BMI higher than 34.7 kg/m².

Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”

He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.

For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.

“Morbid obesity itself is sort of proinflammatory,” he continued.

“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”

Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.

“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
 

Sensitivity needed in public messaging about risks, but test sooner

With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.

Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”

Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”

But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.

And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.

“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.

Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.

Kass and Heymsfield have declared no relevant financial relationships.

This article first appeared on Medscape.com.

The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet.

“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.

The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.

But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.

The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”

“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m²,” he added. “The relationship was pretty tight, pretty quick.”

“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.

Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.

“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.

“We should think of them as a susceptible population.”

Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.

“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
 

Trio of mechanisms explain obesity’s extra COVID-19 risks

Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.

When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.

Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.

The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.

Median BMI among study participants was 29.3 kg/m², with only a quarter having a BMI lower than 26 kg/m² and another 25% having a BMI higher than 34.7 kg/m².

Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”

He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.

For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.

“Morbid obesity itself is sort of proinflammatory,” he continued.

“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”

Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.

“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
 

Sensitivity needed in public messaging about risks, but test sooner

With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.

Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”

Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”

But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.

And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.

“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.

Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.

Kass and Heymsfield have declared no relevant financial relationships.

This article first appeared on Medscape.com.

The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet.

“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.

The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.

But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.

The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”

“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m²,” he added. “The relationship was pretty tight, pretty quick.”

“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.

Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.

“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.

“We should think of them as a susceptible population.”

Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.

“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
 

Trio of mechanisms explain obesity’s extra COVID-19 risks

Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.

When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.

Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.

The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.

Median BMI among study participants was 29.3 kg/m², with only a quarter having a BMI lower than 26 kg/m² and another 25% having a BMI higher than 34.7 kg/m².

Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”

He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.

For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.

“Morbid obesity itself is sort of proinflammatory,” he continued.

“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”

Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.

“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
 

Sensitivity needed in public messaging about risks, but test sooner

With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.

Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”

Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”

But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.

And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.

“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.

Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.

Kass and Heymsfield have declared no relevant financial relationships.

This article first appeared on Medscape.com.

Evolocumab proved effective, well tolerated, and safe for the treatment of refractory dyslipidemia in persons living with HIV in the phase 3, randomized, double-blind BEIJERINCK study.

At 24 weeks, nearly three-quarters of patients randomized to evolocumab (Repatha) achieved at least a 50% reduction in LDL cholesterol while on maximally tolerated background lipid lowering with a statin and/or other drugs. This was accompanied by significant reductions in other atherogenic lipids, Franck Boccara, MD, PhD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Evolocumab thus shows the potential to help fill a major unmet need for more effective treatment of dyslipidemia in HIV-positive patients, who number an estimated 38 million worldwide, including 1.1 million in the United States. Access to highly active antiretroviral therapies has transformed HIV infection into a chronic manageable disease, but this major advance has been accompanied by a rate of premature atherosclerotic cardiovascular disease that’s nearly twice that of the general population, observed Dr. Boccara, a cardiologist at Sorbonne University, Paris.

The BEIJERINCK study included 464 HIV-infected patients in the United States and 14 other countries on five continents. Participants had a mean baseline LDL cholesterol of 133 mg/dL and triglycerides of about 190 mg/dL while on maximally tolerated lipid-lowering therapy. They had been diagnosed with HIV an average of 18 years earlier. One-third of them had known atherosclerotic cardiovascular disease. More than one-quarter of participants were cigarette smokers. Patients were randomized 2:1 to 24 weeks of double-blind subcutaneous evolocumab at 420 mg once monthly or placebo, then an additional 24 weeks of open-label evolocumab for all.

The primary endpoint was change in LDL from baseline to week 24: a 56.2% reduction in the evolocumab group and a 0.7% increase with placebo. About 73% of patients on evolocumab achieved at least a 50% reduction in LDL cholesterol, as did less than 1% of controls. Likewise, 73% of the evolocumab group got their LDL cholesterol below 70 mg/dL, compared with 7.9% with placebo.

The evolocumab group also experienced favorable placebo-subtracted differences from baseline of 23% in triglycerides, 27% in lipoprotein(a), and 22% in very-low-density lipoprotein cholesterol.

As was the case in the earlier, much larger landmark clinical trials, evolocumab was well tolerated in BEIJERINCK, with a side effect profile similar to placebo. Notably, there was no increase in liver abnormalities in evolocumab-treated patients on highly active antiretroviral therapy, and no one developed evolocumab neutralizing antibodies.

Dr. Boccara reported receiving a research grant from Amgen, the study sponsor, as well as lecture fees from several other pharmaceutical companies.

Simultaneous with the presentation at ACC 2020, the primary results of the BEIJERINCK study were published online (J Am Coll Cardiol. 2020 Mar 19. doi: 10.1016/j.jacc.2020.03.025).

bjancin@mdedge.com

Evolocumab proved effective, well tolerated, and safe for the treatment of refractory dyslipidemia in persons living with HIV in the phase 3, randomized, double-blind BEIJERINCK study.

At 24 weeks, nearly three-quarters of patients randomized to evolocumab (Repatha) achieved at least a 50% reduction in LDL cholesterol while on maximally tolerated background lipid lowering with a statin and/or other drugs. This was accompanied by significant reductions in other atherogenic lipids, Franck Boccara, MD, PhD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Evolocumab thus shows the potential to help fill a major unmet need for more effective treatment of dyslipidemia in HIV-positive patients, who number an estimated 38 million worldwide, including 1.1 million in the United States. Access to highly active antiretroviral therapies has transformed HIV infection into a chronic manageable disease, but this major advance has been accompanied by a rate of premature atherosclerotic cardiovascular disease that’s nearly twice that of the general population, observed Dr. Boccara, a cardiologist at Sorbonne University, Paris.

The BEIJERINCK study included 464 HIV-infected patients in the United States and 14 other countries on five continents. Participants had a mean baseline LDL cholesterol of 133 mg/dL and triglycerides of about 190 mg/dL while on maximally tolerated lipid-lowering therapy. They had been diagnosed with HIV an average of 18 years earlier. One-third of them had known atherosclerotic cardiovascular disease. More than one-quarter of participants were cigarette smokers. Patients were randomized 2:1 to 24 weeks of double-blind subcutaneous evolocumab at 420 mg once monthly or placebo, then an additional 24 weeks of open-label evolocumab for all.

The primary endpoint was change in LDL from baseline to week 24: a 56.2% reduction in the evolocumab group and a 0.7% increase with placebo. About 73% of patients on evolocumab achieved at least a 50% reduction in LDL cholesterol, as did less than 1% of controls. Likewise, 73% of the evolocumab group got their LDL cholesterol below 70 mg/dL, compared with 7.9% with placebo.

The evolocumab group also experienced favorable placebo-subtracted differences from baseline of 23% in triglycerides, 27% in lipoprotein(a), and 22% in very-low-density lipoprotein cholesterol.

As was the case in the earlier, much larger landmark clinical trials, evolocumab was well tolerated in BEIJERINCK, with a side effect profile similar to placebo. Notably, there was no increase in liver abnormalities in evolocumab-treated patients on highly active antiretroviral therapy, and no one developed evolocumab neutralizing antibodies.

Dr. Boccara reported receiving a research grant from Amgen, the study sponsor, as well as lecture fees from several other pharmaceutical companies.

Simultaneous with the presentation at ACC 2020, the primary results of the BEIJERINCK study were published online (J Am Coll Cardiol. 2020 Mar 19. doi: 10.1016/j.jacc.2020.03.025).

bjancin@mdedge.com

Evolocumab proved effective, well tolerated, and safe for the treatment of refractory dyslipidemia in persons living with HIV in the phase 3, randomized, double-blind BEIJERINCK study.

At 24 weeks, nearly three-quarters of patients randomized to evolocumab (Repatha) achieved at least a 50% reduction in LDL cholesterol while on maximally tolerated background lipid lowering with a statin and/or other drugs. This was accompanied by significant reductions in other atherogenic lipids, Franck Boccara, MD, PhD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Evolocumab thus shows the potential to help fill a major unmet need for more effective treatment of dyslipidemia in HIV-positive patients, who number an estimated 38 million worldwide, including 1.1 million in the United States. Access to highly active antiretroviral therapies has transformed HIV infection into a chronic manageable disease, but this major advance has been accompanied by a rate of premature atherosclerotic cardiovascular disease that’s nearly twice that of the general population, observed Dr. Boccara, a cardiologist at Sorbonne University, Paris.

The BEIJERINCK study included 464 HIV-infected patients in the United States and 14 other countries on five continents. Participants had a mean baseline LDL cholesterol of 133 mg/dL and triglycerides of about 190 mg/dL while on maximally tolerated lipid-lowering therapy. They had been diagnosed with HIV an average of 18 years earlier. One-third of them had known atherosclerotic cardiovascular disease. More than one-quarter of participants were cigarette smokers. Patients were randomized 2:1 to 24 weeks of double-blind subcutaneous evolocumab at 420 mg once monthly or placebo, then an additional 24 weeks of open-label evolocumab for all.

The primary endpoint was change in LDL from baseline to week 24: a 56.2% reduction in the evolocumab group and a 0.7% increase with placebo. About 73% of patients on evolocumab achieved at least a 50% reduction in LDL cholesterol, as did less than 1% of controls. Likewise, 73% of the evolocumab group got their LDL cholesterol below 70 mg/dL, compared with 7.9% with placebo.

The evolocumab group also experienced favorable placebo-subtracted differences from baseline of 23% in triglycerides, 27% in lipoprotein(a), and 22% in very-low-density lipoprotein cholesterol.

As was the case in the earlier, much larger landmark clinical trials, evolocumab was well tolerated in BEIJERINCK, with a side effect profile similar to placebo. Notably, there was no increase in liver abnormalities in evolocumab-treated patients on highly active antiretroviral therapy, and no one developed evolocumab neutralizing antibodies.

Dr. Boccara reported receiving a research grant from Amgen, the study sponsor, as well as lecture fees from several other pharmaceutical companies.

Simultaneous with the presentation at ACC 2020, the primary results of the BEIJERINCK study were published online (J Am Coll Cardiol. 2020 Mar 19. doi: 10.1016/j.jacc.2020.03.025).

bjancin@mdedge.com