Heart Failure

Treatment with oral tafamidis at 80 mg/day provided a significantly greater survival benefit than dosing at 20 mg/day in patients with transthyretin amyloid cardiomyopathy in the long-term extension of the landmark ATTR-ACT trial, Thibaud Damy, MD, PhD, reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Moreover, the superior survival benefit achieved by taking four 20-mg capsules of tafamidis (Vyndaqel) once daily – or its more convenient once-daily, single-capsule, 61-mg bioequivalent formulation marketed as Vyndamax – came at no cost in terms of side effects and toxicity, compared with low-dose therapy for this progressive multisystem disease, according to Dr. Damy, professor of cardiology at the University of Paris and head of the French National Referral Center for Cardiac Amyloidosis at Henri Mondor University Hospital, Créteil, France.

“There are no side effects with tafamidis,” he said. “It doesn’t act on any receptors, it just acts on the formation of amyloid fibrils, so there are no side effects at whatever dosage is used. And in ATTR-ACT there was actually a trend towards increased side effects in the placebo group because the amyloidosis is everywhere, so by decreasing the amyloidosis process you improve not only the heart but all the organs, and the patient has a better quality of life.”

ATTR-ACT (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) was a phase 3, double-blind study in which 441 patients with transthyretin amyloidosis cardiomyopathy (TAC) in 13 countries were randomized to tafamidis at either 80 mg or 20 mg per day or placebo and followed prospectively for 30 months. At 30 months, all-cause mortality was 29.5% in patients who received tafamidis, compared with 42.9% in controls, for a statistically significant and clinically important 30% relative risk reduction, establishing tafamidis as the first disease-modifying therapy for this disease (N Engl J Med. 2018 Sep 13;379[11]:1007-16).

Patients in the 80-mg group had a 20% reduction in the risk of death, compared with the 20-mg group, at 30 months in an analysis adjusted for baseline age, 6-minute walk distance, and N-terminal pro-B-type natriuretic peptide, all of which are known to impact survival in TAC. This between-group survival difference wasn’t statistically significant, providing one impetus for the subsequent long-term extension study, in which patients remained on their original dose of tafamidis, and the controls who’d been on placebo for 30 months were randomized 2:1 to tafamidis at 80 mg or 20 mg per day.

The primary endpoint in the long-term extension was a composite of all-cause mortality, heart transplantation, or implantation of a ventricular assist device. At a median follow-up of 39 months since ATTR-ACT began, the high-dose tafamidis group had an adjusted 33% reduction in the risk of this endpoint, compared with patients on 20 mg per day, a difference that barely missed statistical significance. At that point, everyone in the long-term extension was switched to the once-daily 61-mg formulation of tafamidis free acid, which is bioequivalent to four 20-mg capsules of tafamidis.

Dr. Damy’s key message: At a median of 51 months of follow-up, the group originally on 80 mg of tafamidis displayed a highly significant adjusted 43% reduction in risk of the composite endpoint, compared with those who had been on 20 mg per day.

Session chair Petar M. Seferovic, MD, PhD, pronounced the ATTR-ACT trial and its long-term extension “a breakthrough advancement.”

“This is the first time in human medical history that we have a drug which improves the long-term outcome, including survival, in patients with this form of hypertrophic cardiomyopathy. So this is extremely important. It’s one of the major steps forward in the treatment of patients with myocardial disease,” said Dr. Seferovic, president of the European Society of Cardiology Heart Failure Association and professor of internal medicine at the University of Belgrade, Serbia.

Discussant Loreena Hill, PhD, of Queen’s University in Belfast, Northern Ireland, observed that TAC is a devastating disease with a formidable symptom burden and an average survival of just 2-5 years after diagnosis.

“It is often underdiagnosed, and yet it is estimated to account for up to 13% of patients with heart failure and preserved ejection fraction,” she said, adding that she considers the long-term extension results “extremely positive.”
 

Nailing down the prevalence of hereditary TAC: the DISCOVERY study

TAC occurs when transthyretin, a transport protein, becomes destabilized and misfolds, promoting deposition of amyloid fibrils in the myocardium and elsewhere. In the heart, the result is progressive ventricular wall thickening and stiffness, manifest as restrictive cardiomyopathy and progressive nonischemic heart failure. The cause of transthyretin destabilization can be either autosomal dominant inheritance of any of more than 100 pathogenic mutations in the transthyretin gene identified to date or a spontaneous wild-type protein.

Dr. Damy was a coinvestigator in the recently published multicenter DISCOVERY study, in which 1,001 patients with clinically suspected cardiac amyloidosis, the great majority of them from the United States, were screened for pathogenic transthyretin genetic mutations. The overall prevalence of such mutations was 8% in the American patients, with the Val122Ile mutation being identified in 11% of African Americans (Amyloid. 2020 May 26;1-8).

The prevalence of wild-type amyloidosis causing TAC hasn’t yet been studied with anything approaching the rigor of DISCOVERY, but the available evidence suggests the wild-type version is roughly as common as the hereditary forms.

Although DISCOVERY and other studies indicate that TAC is far more common than generally realized, Pfizer has priced Vyndaqel and Vyndamax as though TAC is a rare disease, with a U.S. list price of around $225,000 per year.

“Obviously, the cost will go down over time,” Dr. Seferovic predicted.
 

Diagnosing TAC

Audience members mostly wanted to know how to identify individuals with TAC who are buried within the huge population of patients with heart failure with preserved ejection fraction. Dr. Damy said it’s actually a simple matter using a screening framework developed by an 11-member TAC expert panel on which he served. A definitive diagnosis can usually be achieved noninvasively at a low cost using bone scintigraphy, he added.

The panel recommended screening via bone scintigraphy in patients with an increased left ventricular wall thickness of 14 mm or more in men over age 65 and women older than 70 who either have heart failure or red flag symptoms.

These red flags for TAC include an echocardiographic finding of reduced longitudinal strain with relative apical sparing, a discrepancy between left ventricular wall thickness on imaging and normal or low-normal voltages on a standard 12-lead ECG, diffuse gadolinium enhancement or marked extracellular volume expansion on cardiac magnetic resonance imaging, a history of bilateral carpal tunnel syndrome, symptoms of polyneuropathy, and mildly increased serum troponin levels on multiple occasions (JACC Heart Fail. 2019 Aug;7[8]:709-16).

Dr. Damy reported receiving institutional research grant support from Pfizer, the study sponsor, and serving on a scientific advisory board for the company.

bjancin@mdedge.com

Treatment with oral tafamidis at 80 mg/day provided a significantly greater survival benefit than dosing at 20 mg/day in patients with transthyretin amyloid cardiomyopathy in the long-term extension of the landmark ATTR-ACT trial, Thibaud Damy, MD, PhD, reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Moreover, the superior survival benefit achieved by taking four 20-mg capsules of tafamidis (Vyndaqel) once daily – or its more convenient once-daily, single-capsule, 61-mg bioequivalent formulation marketed as Vyndamax – came at no cost in terms of side effects and toxicity, compared with low-dose therapy for this progressive multisystem disease, according to Dr. Damy, professor of cardiology at the University of Paris and head of the French National Referral Center for Cardiac Amyloidosis at Henri Mondor University Hospital, Créteil, France.

“There are no side effects with tafamidis,” he said. “It doesn’t act on any receptors, it just acts on the formation of amyloid fibrils, so there are no side effects at whatever dosage is used. And in ATTR-ACT there was actually a trend towards increased side effects in the placebo group because the amyloidosis is everywhere, so by decreasing the amyloidosis process you improve not only the heart but all the organs, and the patient has a better quality of life.”

ATTR-ACT (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) was a phase 3, double-blind study in which 441 patients with transthyretin amyloidosis cardiomyopathy (TAC) in 13 countries were randomized to tafamidis at either 80 mg or 20 mg per day or placebo and followed prospectively for 30 months. At 30 months, all-cause mortality was 29.5% in patients who received tafamidis, compared with 42.9% in controls, for a statistically significant and clinically important 30% relative risk reduction, establishing tafamidis as the first disease-modifying therapy for this disease (N Engl J Med. 2018 Sep 13;379[11]:1007-16).

Patients in the 80-mg group had a 20% reduction in the risk of death, compared with the 20-mg group, at 30 months in an analysis adjusted for baseline age, 6-minute walk distance, and N-terminal pro-B-type natriuretic peptide, all of which are known to impact survival in TAC. This between-group survival difference wasn’t statistically significant, providing one impetus for the subsequent long-term extension study, in which patients remained on their original dose of tafamidis, and the controls who’d been on placebo for 30 months were randomized 2:1 to tafamidis at 80 mg or 20 mg per day.

The primary endpoint in the long-term extension was a composite of all-cause mortality, heart transplantation, or implantation of a ventricular assist device. At a median follow-up of 39 months since ATTR-ACT began, the high-dose tafamidis group had an adjusted 33% reduction in the risk of this endpoint, compared with patients on 20 mg per day, a difference that barely missed statistical significance. At that point, everyone in the long-term extension was switched to the once-daily 61-mg formulation of tafamidis free acid, which is bioequivalent to four 20-mg capsules of tafamidis.

Dr. Damy’s key message: At a median of 51 months of follow-up, the group originally on 80 mg of tafamidis displayed a highly significant adjusted 43% reduction in risk of the composite endpoint, compared with those who had been on 20 mg per day.

Session chair Petar M. Seferovic, MD, PhD, pronounced the ATTR-ACT trial and its long-term extension “a breakthrough advancement.”

“This is the first time in human medical history that we have a drug which improves the long-term outcome, including survival, in patients with this form of hypertrophic cardiomyopathy. So this is extremely important. It’s one of the major steps forward in the treatment of patients with myocardial disease,” said Dr. Seferovic, president of the European Society of Cardiology Heart Failure Association and professor of internal medicine at the University of Belgrade, Serbia.

Discussant Loreena Hill, PhD, of Queen’s University in Belfast, Northern Ireland, observed that TAC is a devastating disease with a formidable symptom burden and an average survival of just 2-5 years after diagnosis.

“It is often underdiagnosed, and yet it is estimated to account for up to 13% of patients with heart failure and preserved ejection fraction,” she said, adding that she considers the long-term extension results “extremely positive.”
 

Nailing down the prevalence of hereditary TAC: the DISCOVERY study

TAC occurs when transthyretin, a transport protein, becomes destabilized and misfolds, promoting deposition of amyloid fibrils in the myocardium and elsewhere. In the heart, the result is progressive ventricular wall thickening and stiffness, manifest as restrictive cardiomyopathy and progressive nonischemic heart failure. The cause of transthyretin destabilization can be either autosomal dominant inheritance of any of more than 100 pathogenic mutations in the transthyretin gene identified to date or a spontaneous wild-type protein.

Dr. Damy was a coinvestigator in the recently published multicenter DISCOVERY study, in which 1,001 patients with clinically suspected cardiac amyloidosis, the great majority of them from the United States, were screened for pathogenic transthyretin genetic mutations. The overall prevalence of such mutations was 8% in the American patients, with the Val122Ile mutation being identified in 11% of African Americans (Amyloid. 2020 May 26;1-8).

The prevalence of wild-type amyloidosis causing TAC hasn’t yet been studied with anything approaching the rigor of DISCOVERY, but the available evidence suggests the wild-type version is roughly as common as the hereditary forms.

Although DISCOVERY and other studies indicate that TAC is far more common than generally realized, Pfizer has priced Vyndaqel and Vyndamax as though TAC is a rare disease, with a U.S. list price of around $225,000 per year.

“Obviously, the cost will go down over time,” Dr. Seferovic predicted.
 

Diagnosing TAC

Audience members mostly wanted to know how to identify individuals with TAC who are buried within the huge population of patients with heart failure with preserved ejection fraction. Dr. Damy said it’s actually a simple matter using a screening framework developed by an 11-member TAC expert panel on which he served. A definitive diagnosis can usually be achieved noninvasively at a low cost using bone scintigraphy, he added.

The panel recommended screening via bone scintigraphy in patients with an increased left ventricular wall thickness of 14 mm or more in men over age 65 and women older than 70 who either have heart failure or red flag symptoms.

These red flags for TAC include an echocardiographic finding of reduced longitudinal strain with relative apical sparing, a discrepancy between left ventricular wall thickness on imaging and normal or low-normal voltages on a standard 12-lead ECG, diffuse gadolinium enhancement or marked extracellular volume expansion on cardiac magnetic resonance imaging, a history of bilateral carpal tunnel syndrome, symptoms of polyneuropathy, and mildly increased serum troponin levels on multiple occasions (JACC Heart Fail. 2019 Aug;7[8]:709-16).

Dr. Damy reported receiving institutional research grant support from Pfizer, the study sponsor, and serving on a scientific advisory board for the company.

bjancin@mdedge.com

Treatment with oral tafamidis at 80 mg/day provided a significantly greater survival benefit than dosing at 20 mg/day in patients with transthyretin amyloid cardiomyopathy in the long-term extension of the landmark ATTR-ACT trial, Thibaud Damy, MD, PhD, reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Moreover, the superior survival benefit achieved by taking four 20-mg capsules of tafamidis (Vyndaqel) once daily – or its more convenient once-daily, single-capsule, 61-mg bioequivalent formulation marketed as Vyndamax – came at no cost in terms of side effects and toxicity, compared with low-dose therapy for this progressive multisystem disease, according to Dr. Damy, professor of cardiology at the University of Paris and head of the French National Referral Center for Cardiac Amyloidosis at Henri Mondor University Hospital, Créteil, France.

“There are no side effects with tafamidis,” he said. “It doesn’t act on any receptors, it just acts on the formation of amyloid fibrils, so there are no side effects at whatever dosage is used. And in ATTR-ACT there was actually a trend towards increased side effects in the placebo group because the amyloidosis is everywhere, so by decreasing the amyloidosis process you improve not only the heart but all the organs, and the patient has a better quality of life.”

ATTR-ACT (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) was a phase 3, double-blind study in which 441 patients with transthyretin amyloidosis cardiomyopathy (TAC) in 13 countries were randomized to tafamidis at either 80 mg or 20 mg per day or placebo and followed prospectively for 30 months. At 30 months, all-cause mortality was 29.5% in patients who received tafamidis, compared with 42.9% in controls, for a statistically significant and clinically important 30% relative risk reduction, establishing tafamidis as the first disease-modifying therapy for this disease (N Engl J Med. 2018 Sep 13;379[11]:1007-16).

Patients in the 80-mg group had a 20% reduction in the risk of death, compared with the 20-mg group, at 30 months in an analysis adjusted for baseline age, 6-minute walk distance, and N-terminal pro-B-type natriuretic peptide, all of which are known to impact survival in TAC. This between-group survival difference wasn’t statistically significant, providing one impetus for the subsequent long-term extension study, in which patients remained on their original dose of tafamidis, and the controls who’d been on placebo for 30 months were randomized 2:1 to tafamidis at 80 mg or 20 mg per day.

The primary endpoint in the long-term extension was a composite of all-cause mortality, heart transplantation, or implantation of a ventricular assist device. At a median follow-up of 39 months since ATTR-ACT began, the high-dose tafamidis group had an adjusted 33% reduction in the risk of this endpoint, compared with patients on 20 mg per day, a difference that barely missed statistical significance. At that point, everyone in the long-term extension was switched to the once-daily 61-mg formulation of tafamidis free acid, which is bioequivalent to four 20-mg capsules of tafamidis.

Dr. Damy’s key message: At a median of 51 months of follow-up, the group originally on 80 mg of tafamidis displayed a highly significant adjusted 43% reduction in risk of the composite endpoint, compared with those who had been on 20 mg per day.

Session chair Petar M. Seferovic, MD, PhD, pronounced the ATTR-ACT trial and its long-term extension “a breakthrough advancement.”

“This is the first time in human medical history that we have a drug which improves the long-term outcome, including survival, in patients with this form of hypertrophic cardiomyopathy. So this is extremely important. It’s one of the major steps forward in the treatment of patients with myocardial disease,” said Dr. Seferovic, president of the European Society of Cardiology Heart Failure Association and professor of internal medicine at the University of Belgrade, Serbia.

Discussant Loreena Hill, PhD, of Queen’s University in Belfast, Northern Ireland, observed that TAC is a devastating disease with a formidable symptom burden and an average survival of just 2-5 years after diagnosis.

“It is often underdiagnosed, and yet it is estimated to account for up to 13% of patients with heart failure and preserved ejection fraction,” she said, adding that she considers the long-term extension results “extremely positive.”
 

Nailing down the prevalence of hereditary TAC: the DISCOVERY study

TAC occurs when transthyretin, a transport protein, becomes destabilized and misfolds, promoting deposition of amyloid fibrils in the myocardium and elsewhere. In the heart, the result is progressive ventricular wall thickening and stiffness, manifest as restrictive cardiomyopathy and progressive nonischemic heart failure. The cause of transthyretin destabilization can be either autosomal dominant inheritance of any of more than 100 pathogenic mutations in the transthyretin gene identified to date or a spontaneous wild-type protein.

Dr. Damy was a coinvestigator in the recently published multicenter DISCOVERY study, in which 1,001 patients with clinically suspected cardiac amyloidosis, the great majority of them from the United States, were screened for pathogenic transthyretin genetic mutations. The overall prevalence of such mutations was 8% in the American patients, with the Val122Ile mutation being identified in 11% of African Americans (Amyloid. 2020 May 26;1-8).

The prevalence of wild-type amyloidosis causing TAC hasn’t yet been studied with anything approaching the rigor of DISCOVERY, but the available evidence suggests the wild-type version is roughly as common as the hereditary forms.

Although DISCOVERY and other studies indicate that TAC is far more common than generally realized, Pfizer has priced Vyndaqel and Vyndamax as though TAC is a rare disease, with a U.S. list price of around $225,000 per year.

“Obviously, the cost will go down over time,” Dr. Seferovic predicted.
 

Diagnosing TAC

Audience members mostly wanted to know how to identify individuals with TAC who are buried within the huge population of patients with heart failure with preserved ejection fraction. Dr. Damy said it’s actually a simple matter using a screening framework developed by an 11-member TAC expert panel on which he served. A definitive diagnosis can usually be achieved noninvasively at a low cost using bone scintigraphy, he added.

The panel recommended screening via bone scintigraphy in patients with an increased left ventricular wall thickness of 14 mm or more in men over age 65 and women older than 70 who either have heart failure or red flag symptoms.

These red flags for TAC include an echocardiographic finding of reduced longitudinal strain with relative apical sparing, a discrepancy between left ventricular wall thickness on imaging and normal or low-normal voltages on a standard 12-lead ECG, diffuse gadolinium enhancement or marked extracellular volume expansion on cardiac magnetic resonance imaging, a history of bilateral carpal tunnel syndrome, symptoms of polyneuropathy, and mildly increased serum troponin levels on multiple occasions (JACC Heart Fail. 2019 Aug;7[8]:709-16).

Dr. Damy reported receiving institutional research grant support from Pfizer, the study sponsor, and serving on a scientific advisory board for the company.

bjancin@mdedge.com

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.

“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.

It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.

“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”

Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.

The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m² who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.

The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.

The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.

Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.

“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.

It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.

“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”

Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.

The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m² who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.

The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.

The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.

Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.

“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.

It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.

“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”

Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.

The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m² who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.

The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.

The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.

Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.

A version of this article originally appeared on Medscape.com.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.

The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.

The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.

The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.

The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.

Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.

A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.

Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.

bjancin@mdedge.com

Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.

The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.

The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.

The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.

The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.

Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.

A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.

Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.

bjancin@mdedge.com

Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.

The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.

The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.

The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.

The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.

Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.

A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.

Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.

bjancin@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.

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.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com