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30-day readmissions after STEMI with cardiogenic shock 13%
WASHINGTON – and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.
Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.
In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.
Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.
The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.
“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.
“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.
WASHINGTON – and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.
Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.
In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.
Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.
The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.
“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.
“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.
WASHINGTON – and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.
Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.
In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.
Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.
The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.
“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.
“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.
REPORTING FROM CRT 2019
FDA: Programmable heart failure device approved
. Specifically, these patients are unsuited for other treatments, have marked physical limitations related to their heart failure, and have remained symptomatic despite optimal medical therapy. They also have a regular heart rhythm, are not candidates for resynchronization, and possess a left ventricular ejection fraction of 25%-45%.
The cardiac contractility modulation system is indicated to improve 6-minute hall walk distance, quality of life, and functional status in these patients.
The system is made up of several components, including the implantable pulse generator, a programmer, and software. The pulse generator is connected to three leads that have been implanted in the heart, after which the device is tested and programmed to deliver pulses during normal heartbeats, which improves the heart’s squeezing capability. In randomized, multicenter clinical trials, the system plus optimal medical therapy demonstrated improvements in distance during 6-minute walking tests and standard assessments of heart failure symptoms when compared with optimal medical therapy alone.
The Breakthrough Device designation means this system treats a life-threatening disease and addresses unmet medical needs among some patients. “The FDA recognized the unmet need for these patients and worked with the manufacturer through our Breakthrough Device Program to efficiently bring this product to market, while ensuring it meets our regulatory requirements for safety and effectiveness,” Bram Zuckerman, MD, the director of the division of cardiovascular devices in the FDA’s Center for Devices and Radiological Health said in a news release from the agency.
. Specifically, these patients are unsuited for other treatments, have marked physical limitations related to their heart failure, and have remained symptomatic despite optimal medical therapy. They also have a regular heart rhythm, are not candidates for resynchronization, and possess a left ventricular ejection fraction of 25%-45%.
The cardiac contractility modulation system is indicated to improve 6-minute hall walk distance, quality of life, and functional status in these patients.
The system is made up of several components, including the implantable pulse generator, a programmer, and software. The pulse generator is connected to three leads that have been implanted in the heart, after which the device is tested and programmed to deliver pulses during normal heartbeats, which improves the heart’s squeezing capability. In randomized, multicenter clinical trials, the system plus optimal medical therapy demonstrated improvements in distance during 6-minute walking tests and standard assessments of heart failure symptoms when compared with optimal medical therapy alone.
The Breakthrough Device designation means this system treats a life-threatening disease and addresses unmet medical needs among some patients. “The FDA recognized the unmet need for these patients and worked with the manufacturer through our Breakthrough Device Program to efficiently bring this product to market, while ensuring it meets our regulatory requirements for safety and effectiveness,” Bram Zuckerman, MD, the director of the division of cardiovascular devices in the FDA’s Center for Devices and Radiological Health said in a news release from the agency.
. Specifically, these patients are unsuited for other treatments, have marked physical limitations related to their heart failure, and have remained symptomatic despite optimal medical therapy. They also have a regular heart rhythm, are not candidates for resynchronization, and possess a left ventricular ejection fraction of 25%-45%.
The cardiac contractility modulation system is indicated to improve 6-minute hall walk distance, quality of life, and functional status in these patients.
The system is made up of several components, including the implantable pulse generator, a programmer, and software. The pulse generator is connected to three leads that have been implanted in the heart, after which the device is tested and programmed to deliver pulses during normal heartbeats, which improves the heart’s squeezing capability. In randomized, multicenter clinical trials, the system plus optimal medical therapy demonstrated improvements in distance during 6-minute walking tests and standard assessments of heart failure symptoms when compared with optimal medical therapy alone.
The Breakthrough Device designation means this system treats a life-threatening disease and addresses unmet medical needs among some patients. “The FDA recognized the unmet need for these patients and worked with the manufacturer through our Breakthrough Device Program to efficiently bring this product to market, while ensuring it meets our regulatory requirements for safety and effectiveness,” Bram Zuckerman, MD, the director of the division of cardiovascular devices in the FDA’s Center for Devices and Radiological Health said in a news release from the agency.
MitraClip improves survival and health status for at least 2 years
, based on results from a substudy of the COAPT trial.
Significant improvements seen at 1 month in the TMVr group had waned only slightly by the 2-year time point, reported lead author Suzanne V. Arnold, MD, of Saint Luke’s Mid America Heart Institute and University of Missouri–Kansas City, who presented the findings at the annual meeting of the American College of Cardiology. The study was simultaneously published in the Journal of the American College of Cardiology.
“Considering the previously reported benefits of TMVr on survival and heart failure hospitalization, these health status findings further support the device as a valuable treatment option for heart failure patients with severe secondary mitral regurgitation who remain symptomatic despite maximally-tolerated guideline-directed medical therapy,” Dr. Arnold and her colleagues concluded.
Primary findings from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial showed that TMVr reduced hospitalizations due to heart failure and all-cause mortality over 2 years, leading the Food and Drug Administration to grant an extended indication to MitraClip. With the present substudy, the investigators sought to learn more about impacts of TMVr on overall health.
“Beyond prolonging survival and reducing hospitalizations, improving patients’ health status (i.e., symptoms, functional status, quality of life) is a key treatment goal of TMVr,” the investigators wrote. “In fact, among older patients with comorbidities and high symptom burden, health status improvement may be of greater importance to patients than improved survival.”
To measure these outcomes, the investigators employed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey, which they administered to 302 patients in the TMVr group and 312 patients in the standard care group. The primary endpoint was the KCCQ overall summary score (KCCQ-OS), which ranges from 0 to 100, with higher scores indicating better health status.
Across all patients, the average baseline KCCQ-OS score was 52.4 ± 23.0. After 1 month, the average KCCQ-OS score rose 2.1 points in the standard care group, while the TMVr group saw a 16.9-point increase, most heavily through the questionnaire’s quality of life domain. These figures translate to a mean between-group difference of 15.9 points, a value that decreased only slightly after 2 years, to 12.8 points. Further suggesting that TMVr had beneficial and lasting effects, a significantly greater percentage of patients in the TMVr group than in the standard care group were alive with a moderately large health improvement after 2 years (36.4% vs 16.6%; P less than .001).
The study was funded by Abbott Vascular. Several of the investigators reported financial relationships with Abbott as well as Novartis, Bayer, V-wave, Corvia, and others.
SOURCE: Arnold et al. J Am Coll Cardiol. 2019 Mar 17.
, based on results from a substudy of the COAPT trial.
Significant improvements seen at 1 month in the TMVr group had waned only slightly by the 2-year time point, reported lead author Suzanne V. Arnold, MD, of Saint Luke’s Mid America Heart Institute and University of Missouri–Kansas City, who presented the findings at the annual meeting of the American College of Cardiology. The study was simultaneously published in the Journal of the American College of Cardiology.
“Considering the previously reported benefits of TMVr on survival and heart failure hospitalization, these health status findings further support the device as a valuable treatment option for heart failure patients with severe secondary mitral regurgitation who remain symptomatic despite maximally-tolerated guideline-directed medical therapy,” Dr. Arnold and her colleagues concluded.
Primary findings from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial showed that TMVr reduced hospitalizations due to heart failure and all-cause mortality over 2 years, leading the Food and Drug Administration to grant an extended indication to MitraClip. With the present substudy, the investigators sought to learn more about impacts of TMVr on overall health.
“Beyond prolonging survival and reducing hospitalizations, improving patients’ health status (i.e., symptoms, functional status, quality of life) is a key treatment goal of TMVr,” the investigators wrote. “In fact, among older patients with comorbidities and high symptom burden, health status improvement may be of greater importance to patients than improved survival.”
To measure these outcomes, the investigators employed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey, which they administered to 302 patients in the TMVr group and 312 patients in the standard care group. The primary endpoint was the KCCQ overall summary score (KCCQ-OS), which ranges from 0 to 100, with higher scores indicating better health status.
Across all patients, the average baseline KCCQ-OS score was 52.4 ± 23.0. After 1 month, the average KCCQ-OS score rose 2.1 points in the standard care group, while the TMVr group saw a 16.9-point increase, most heavily through the questionnaire’s quality of life domain. These figures translate to a mean between-group difference of 15.9 points, a value that decreased only slightly after 2 years, to 12.8 points. Further suggesting that TMVr had beneficial and lasting effects, a significantly greater percentage of patients in the TMVr group than in the standard care group were alive with a moderately large health improvement after 2 years (36.4% vs 16.6%; P less than .001).
The study was funded by Abbott Vascular. Several of the investigators reported financial relationships with Abbott as well as Novartis, Bayer, V-wave, Corvia, and others.
SOURCE: Arnold et al. J Am Coll Cardiol. 2019 Mar 17.
, based on results from a substudy of the COAPT trial.
Significant improvements seen at 1 month in the TMVr group had waned only slightly by the 2-year time point, reported lead author Suzanne V. Arnold, MD, of Saint Luke’s Mid America Heart Institute and University of Missouri–Kansas City, who presented the findings at the annual meeting of the American College of Cardiology. The study was simultaneously published in the Journal of the American College of Cardiology.
“Considering the previously reported benefits of TMVr on survival and heart failure hospitalization, these health status findings further support the device as a valuable treatment option for heart failure patients with severe secondary mitral regurgitation who remain symptomatic despite maximally-tolerated guideline-directed medical therapy,” Dr. Arnold and her colleagues concluded.
Primary findings from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial showed that TMVr reduced hospitalizations due to heart failure and all-cause mortality over 2 years, leading the Food and Drug Administration to grant an extended indication to MitraClip. With the present substudy, the investigators sought to learn more about impacts of TMVr on overall health.
“Beyond prolonging survival and reducing hospitalizations, improving patients’ health status (i.e., symptoms, functional status, quality of life) is a key treatment goal of TMVr,” the investigators wrote. “In fact, among older patients with comorbidities and high symptom burden, health status improvement may be of greater importance to patients than improved survival.”
To measure these outcomes, the investigators employed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey, which they administered to 302 patients in the TMVr group and 312 patients in the standard care group. The primary endpoint was the KCCQ overall summary score (KCCQ-OS), which ranges from 0 to 100, with higher scores indicating better health status.
Across all patients, the average baseline KCCQ-OS score was 52.4 ± 23.0. After 1 month, the average KCCQ-OS score rose 2.1 points in the standard care group, while the TMVr group saw a 16.9-point increase, most heavily through the questionnaire’s quality of life domain. These figures translate to a mean between-group difference of 15.9 points, a value that decreased only slightly after 2 years, to 12.8 points. Further suggesting that TMVr had beneficial and lasting effects, a significantly greater percentage of patients in the TMVr group than in the standard care group were alive with a moderately large health improvement after 2 years (36.4% vs 16.6%; P less than .001).
The study was funded by Abbott Vascular. Several of the investigators reported financial relationships with Abbott as well as Novartis, Bayer, V-wave, Corvia, and others.
SOURCE: Arnold et al. J Am Coll Cardiol. 2019 Mar 17.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
FDA approves new valsartan generic
In response to a medication shortage, the Food and Drug Administration has approved a new generic of valsartan (Diovan), produced by Alkem Laboratories, for the treatment of high blood pressure and heart failure, the regulatory agency announced in a statement.
The FDA conducted an investigation into generic angiotensin II receptor blocker (ARB) products following reports of N-nitrosodimethylamine impurities being found in a separate valsartan product in the summer of 2018. Since that time, nitrosamine impurities have been detected in multiple ARBs, and as of March 1, 2019, hundreds of lots of ARBs produced by several companies have been recalled. The FDA has implemented new rules to prevent further contamination, but the ongoing recalls have caused a significant shortage.
“[To] address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA commissioner Scott Gottlieb, MD, said in the statement.
For the new generic’s approval, the FDA assessed Alkem Laboratories’ manufacturing process and ensured that the company used proper testing methods to rule out the presence of nitrosamine impurities.
“We hope that today’s approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products,” Dr. Gottlieb said.
In response to a medication shortage, the Food and Drug Administration has approved a new generic of valsartan (Diovan), produced by Alkem Laboratories, for the treatment of high blood pressure and heart failure, the regulatory agency announced in a statement.
The FDA conducted an investigation into generic angiotensin II receptor blocker (ARB) products following reports of N-nitrosodimethylamine impurities being found in a separate valsartan product in the summer of 2018. Since that time, nitrosamine impurities have been detected in multiple ARBs, and as of March 1, 2019, hundreds of lots of ARBs produced by several companies have been recalled. The FDA has implemented new rules to prevent further contamination, but the ongoing recalls have caused a significant shortage.
“[To] address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA commissioner Scott Gottlieb, MD, said in the statement.
For the new generic’s approval, the FDA assessed Alkem Laboratories’ manufacturing process and ensured that the company used proper testing methods to rule out the presence of nitrosamine impurities.
“We hope that today’s approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products,” Dr. Gottlieb said.
In response to a medication shortage, the Food and Drug Administration has approved a new generic of valsartan (Diovan), produced by Alkem Laboratories, for the treatment of high blood pressure and heart failure, the regulatory agency announced in a statement.
The FDA conducted an investigation into generic angiotensin II receptor blocker (ARB) products following reports of N-nitrosodimethylamine impurities being found in a separate valsartan product in the summer of 2018. Since that time, nitrosamine impurities have been detected in multiple ARBs, and as of March 1, 2019, hundreds of lots of ARBs produced by several companies have been recalled. The FDA has implemented new rules to prevent further contamination, but the ongoing recalls have caused a significant shortage.
“[To] address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA commissioner Scott Gottlieb, MD, said in the statement.
For the new generic’s approval, the FDA assessed Alkem Laboratories’ manufacturing process and ensured that the company used proper testing methods to rule out the presence of nitrosamine impurities.
“We hope that today’s approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products,” Dr. Gottlieb said.
Newer antihyperglycemic drugs have distinctive CV, kidney benefits
The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.
The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.
“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.
Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.
The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.
Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.
Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.
By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.
Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.
“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.
Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.
Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.
Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.
SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.
The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.
The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.
“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.
Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.
The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.
Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.
Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.
By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.
Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.
“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.
Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.
Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.
Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.
SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.
The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.
The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.
“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.
Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.
The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.
Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.
Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.
By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.
Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.
“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.
Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.
Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.
Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.
SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.
FROM CIRCULATION
Five pitfalls in optimizing medical management of HFrEF
SNOWMASS, COLO. – Many of the abundant missed opportunities to optimize pharmacotherapy for heart failure with reduced ejection fraction revolve around not getting fully on board with the guideline-directed medical therapy shown to be highly effective at improving clinical outcomes, Akshay S. Desai, MD, asserted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“If you take nothing else away from this talk, is really quite profound,” declared Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, and a cardiologist at Harvard Medical School, Boston.
He highlighted five common traps or pitfalls for physicians with regard to medical therapy of patients with heart failure with reduced ejection fraction (HFrEF):
Underutilization of guideline-directed medical therapy
The current ACC/American Heart Association/Heart Failure Society of America guidelines on heart failure management (Circulation. 2017 Aug 8;136[6]:e137-61) reflect 20 years of impressive progress in improving heart failure outcomes through the use of increasingly effective guideline-directed medical therapy (GDMT). The magnitude of this improvement was nicely captured in a meta-analysis of 57 randomized controlled trials published during 1987-2015. The meta-analysis showed that, although ACE inhibitor therapy alone had no significant impact on all-cause mortality compared to placebo in patients with HFrEF, the sequential addition of guideline-directed drugs conferred stepwise improvements in survival. This approach culminated in a 56% reduction in all-cause mortality with the combination of an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), compared with placebo, and a 63% reduction with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and MRA (Circ Heart Fail. 2017 Jan;10(1). pii: e003529).
Moreover, the benefits of contemporary GDMT extend beyond reductions in all-cause mortality, death due to heart failure, and heart failure–related hospitalizations into areas where one wouldn’t necessarily have expected to see much benefit. For example, an analysis of data on more than 40,000 HFrEF patients in 12 clinical trials showed a sharp decline in the rate of sudden death over the years as new agents were incorporated into GDMT. The cumulative incidence of sudden death within 90 days after randomization plunged from 2.4% in the earliest trial to 1.0% in the most recent one (N Engl J Med. 2017 Jul 6;377[1]:41-51).
“We’re at the point where we now question whether routine use of implantable cardioverter-defibrillators in primary prevention patients with nonischemic heart failure is really worthwhile on the backdrop of effective medical therapy,” Dr. Desai observed.
But there’s a problem: “We don’t do a great job with GDMT, even with this incredible evidence base that we have,” the cardiologist said.
He cited a report from the CHAMP-HF registry that scrutinized the use of GDMT in more than 3,500 ambulatory HFrEF patients in 150 U.S. primary care and cardiology practices. It found that 67% of patients deemed eligible for an MRA weren’t on one. Neither were 33% with no contraindications to beta-blocker therapy and 27% who were eligible for an ACE inhibitor, angiotensin receptor blocker (ARB), or ARNI (J Am Coll Cardiol. 2018 Jul 24;72[4]:351-66).
“This highlights a huge opportunity for further guideline-directed optimization of therapy,” he said.
Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (JACC Heart Fail. 2016 Oct;4[10]:816-22). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”
Inadequate laboratory monitoring
The MRAs, spironolactone and eplerenone (Inspra), are the GDMT drugs for which laboratory surveillance takes on the greatest importance because of their potential to induce hyperkalemia. The guidelines are clear that a potassium level and measurement of renal function should be obtained within a week of initiating therapy with an MRA, again at 4 weeks, and periodically thereafter.
“In general, this is done in clinical practice almost never,” Dr. Desai stressed.
These agents should be avoided in patients with prior hyperkalemia or advanced chronic kidney disease, and used with care in groups known to be at increased risk for hyperkalemia, including the elderly and patients with diabetes.
He considers spironolactone equivalent to eplerenone so long as the dosing is adequate. He generally reserves eplerenone for patients with poorly tolerated antiandrogenic effects on spironolactone.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
SNOWMASS, COLO. – Many of the abundant missed opportunities to optimize pharmacotherapy for heart failure with reduced ejection fraction revolve around not getting fully on board with the guideline-directed medical therapy shown to be highly effective at improving clinical outcomes, Akshay S. Desai, MD, asserted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“If you take nothing else away from this talk, is really quite profound,” declared Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, and a cardiologist at Harvard Medical School, Boston.
He highlighted five common traps or pitfalls for physicians with regard to medical therapy of patients with heart failure with reduced ejection fraction (HFrEF):
Underutilization of guideline-directed medical therapy
The current ACC/American Heart Association/Heart Failure Society of America guidelines on heart failure management (Circulation. 2017 Aug 8;136[6]:e137-61) reflect 20 years of impressive progress in improving heart failure outcomes through the use of increasingly effective guideline-directed medical therapy (GDMT). The magnitude of this improvement was nicely captured in a meta-analysis of 57 randomized controlled trials published during 1987-2015. The meta-analysis showed that, although ACE inhibitor therapy alone had no significant impact on all-cause mortality compared to placebo in patients with HFrEF, the sequential addition of guideline-directed drugs conferred stepwise improvements in survival. This approach culminated in a 56% reduction in all-cause mortality with the combination of an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), compared with placebo, and a 63% reduction with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and MRA (Circ Heart Fail. 2017 Jan;10(1). pii: e003529).
Moreover, the benefits of contemporary GDMT extend beyond reductions in all-cause mortality, death due to heart failure, and heart failure–related hospitalizations into areas where one wouldn’t necessarily have expected to see much benefit. For example, an analysis of data on more than 40,000 HFrEF patients in 12 clinical trials showed a sharp decline in the rate of sudden death over the years as new agents were incorporated into GDMT. The cumulative incidence of sudden death within 90 days after randomization plunged from 2.4% in the earliest trial to 1.0% in the most recent one (N Engl J Med. 2017 Jul 6;377[1]:41-51).
“We’re at the point where we now question whether routine use of implantable cardioverter-defibrillators in primary prevention patients with nonischemic heart failure is really worthwhile on the backdrop of effective medical therapy,” Dr. Desai observed.
But there’s a problem: “We don’t do a great job with GDMT, even with this incredible evidence base that we have,” the cardiologist said.
He cited a report from the CHAMP-HF registry that scrutinized the use of GDMT in more than 3,500 ambulatory HFrEF patients in 150 U.S. primary care and cardiology practices. It found that 67% of patients deemed eligible for an MRA weren’t on one. Neither were 33% with no contraindications to beta-blocker therapy and 27% who were eligible for an ACE inhibitor, angiotensin receptor blocker (ARB), or ARNI (J Am Coll Cardiol. 2018 Jul 24;72[4]:351-66).
“This highlights a huge opportunity for further guideline-directed optimization of therapy,” he said.
Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (JACC Heart Fail. 2016 Oct;4[10]:816-22). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”
Inadequate laboratory monitoring
The MRAs, spironolactone and eplerenone (Inspra), are the GDMT drugs for which laboratory surveillance takes on the greatest importance because of their potential to induce hyperkalemia. The guidelines are clear that a potassium level and measurement of renal function should be obtained within a week of initiating therapy with an MRA, again at 4 weeks, and periodically thereafter.
“In general, this is done in clinical practice almost never,” Dr. Desai stressed.
These agents should be avoided in patients with prior hyperkalemia or advanced chronic kidney disease, and used with care in groups known to be at increased risk for hyperkalemia, including the elderly and patients with diabetes.
He considers spironolactone equivalent to eplerenone so long as the dosing is adequate. He generally reserves eplerenone for patients with poorly tolerated antiandrogenic effects on spironolactone.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
SNOWMASS, COLO. – Many of the abundant missed opportunities to optimize pharmacotherapy for heart failure with reduced ejection fraction revolve around not getting fully on board with the guideline-directed medical therapy shown to be highly effective at improving clinical outcomes, Akshay S. Desai, MD, asserted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“If you take nothing else away from this talk, is really quite profound,” declared Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, and a cardiologist at Harvard Medical School, Boston.
He highlighted five common traps or pitfalls for physicians with regard to medical therapy of patients with heart failure with reduced ejection fraction (HFrEF):
Underutilization of guideline-directed medical therapy
The current ACC/American Heart Association/Heart Failure Society of America guidelines on heart failure management (Circulation. 2017 Aug 8;136[6]:e137-61) reflect 20 years of impressive progress in improving heart failure outcomes through the use of increasingly effective guideline-directed medical therapy (GDMT). The magnitude of this improvement was nicely captured in a meta-analysis of 57 randomized controlled trials published during 1987-2015. The meta-analysis showed that, although ACE inhibitor therapy alone had no significant impact on all-cause mortality compared to placebo in patients with HFrEF, the sequential addition of guideline-directed drugs conferred stepwise improvements in survival. This approach culminated in a 56% reduction in all-cause mortality with the combination of an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), compared with placebo, and a 63% reduction with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and MRA (Circ Heart Fail. 2017 Jan;10(1). pii: e003529).
Moreover, the benefits of contemporary GDMT extend beyond reductions in all-cause mortality, death due to heart failure, and heart failure–related hospitalizations into areas where one wouldn’t necessarily have expected to see much benefit. For example, an analysis of data on more than 40,000 HFrEF patients in 12 clinical trials showed a sharp decline in the rate of sudden death over the years as new agents were incorporated into GDMT. The cumulative incidence of sudden death within 90 days after randomization plunged from 2.4% in the earliest trial to 1.0% in the most recent one (N Engl J Med. 2017 Jul 6;377[1]:41-51).
“We’re at the point where we now question whether routine use of implantable cardioverter-defibrillators in primary prevention patients with nonischemic heart failure is really worthwhile on the backdrop of effective medical therapy,” Dr. Desai observed.
But there’s a problem: “We don’t do a great job with GDMT, even with this incredible evidence base that we have,” the cardiologist said.
He cited a report from the CHAMP-HF registry that scrutinized the use of GDMT in more than 3,500 ambulatory HFrEF patients in 150 U.S. primary care and cardiology practices. It found that 67% of patients deemed eligible for an MRA weren’t on one. Neither were 33% with no contraindications to beta-blocker therapy and 27% who were eligible for an ACE inhibitor, angiotensin receptor blocker (ARB), or ARNI (J Am Coll Cardiol. 2018 Jul 24;72[4]:351-66).
“This highlights a huge opportunity for further guideline-directed optimization of therapy,” he said.
Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (JACC Heart Fail. 2016 Oct;4[10]:816-22). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”
Inadequate laboratory monitoring
The MRAs, spironolactone and eplerenone (Inspra), are the GDMT drugs for which laboratory surveillance takes on the greatest importance because of their potential to induce hyperkalemia. The guidelines are clear that a potassium level and measurement of renal function should be obtained within a week of initiating therapy with an MRA, again at 4 weeks, and periodically thereafter.
“In general, this is done in clinical practice almost never,” Dr. Desai stressed.
These agents should be avoided in patients with prior hyperkalemia or advanced chronic kidney disease, and used with care in groups known to be at increased risk for hyperkalemia, including the elderly and patients with diabetes.
He considers spironolactone equivalent to eplerenone so long as the dosing is adequate. He generally reserves eplerenone for patients with poorly tolerated antiandrogenic effects on spironolactone.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
REPORTING FROM ACC SNOWMASS 2019
Forget what you learned about infective endocarditis
This week in MDedge Cardiocast: Infective endocarditis isn’t what it used to be, there’s a new, lower goal for Americans’ dietary intake of sodium, a drug to treat multiple myeloma also raises heart failure risk, and Big Pharma says it can’t drop drug list prices alone.
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Apple Podcasts
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TuneIn
This week in MDedge Cardiocast: Infective endocarditis isn’t what it used to be, there’s a new, lower goal for Americans’ dietary intake of sodium, a drug to treat multiple myeloma also raises heart failure risk, and Big Pharma says it can’t drop drug list prices alone.
Amazon Alexa
Apple Podcasts
Google Podcasts
TuneIn
This week in MDedge Cardiocast: Infective endocarditis isn’t what it used to be, there’s a new, lower goal for Americans’ dietary intake of sodium, a drug to treat multiple myeloma also raises heart failure risk, and Big Pharma says it can’t drop drug list prices alone.
Amazon Alexa
Apple Podcasts
Google Podcasts
TuneIn
Infective endocarditis isn’t what it used to be
SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.
“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.
“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.
This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
Outcomes are ‘sobering’
In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.
Refer early for multimodality imaging and surgical consultation
Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.
The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).
Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.
If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.
“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.
The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
Don’t use half measures when it comes to removal of cardiac implanted electronic devices
The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.
“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
Know when the cardiologist should say ‘no’ to early aggressive surgery
While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.
“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.
“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.
This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
Outcomes are ‘sobering’
In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.
Refer early for multimodality imaging and surgical consultation
Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.
The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).
Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.
If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.
“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.
The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
Don’t use half measures when it comes to removal of cardiac implanted electronic devices
The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.
“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
Know when the cardiologist should say ‘no’ to early aggressive surgery
While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.
“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.
“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.
This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
Outcomes are ‘sobering’
In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.
Refer early for multimodality imaging and surgical consultation
Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.
The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).
Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.
If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.
“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.
The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
Don’t use half measures when it comes to removal of cardiac implanted electronic devices
The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.
“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
Know when the cardiologist should say ‘no’ to early aggressive surgery
While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
REPORTING FROM ACC SNOWMASS 2019
Commentary: Should AVFs be ligated after kidney transplant?
Hemodynamic complications of arteriovenous (AV) access are uncommon but can be potentially life threatening. Fistulas and grafts can cause a decrease in systemic vascular resistance and secondary increase in cardiac output in patients who may already have myocardial dysfunction secondary to their end-stage renal disease.1 This increased cardiac output is usually insignificant but in rare cases can result in clinically significant cardiac failure. Patients with high-output fistulas with volume flow greater than 2 L/min may be at increased risk of heart failure but volume flow less than 2 L/min does not preclude this complication.2
In patients with AV access–related heart failure, optimal medical management and reduction of fistula flow or ligation of the dialysis access should be considered. If continued hemodialysis is necessary, loss of a functioning dialysis access is problematic and difficult management decisions must be made. Following successful renal transplantation, ligation of vascular access in the presence of symptomatic heart failure may represent a straightforward decision. Nonetheless, there is no clear consensus of how to manage patent fistulas or grafts in patients following renal transplantation in the absence of significant cardiac symptoms with particular concern to the important issues of transplant survival and long-term cardiac prognosis. Yaffe and Greenstein3 recommend preservation of almost all fistulas after transplantation in the absence of significant complications such as venous hypertension, pseudoaneurysm, significant high-output cardiac failure or hand ischemia. They recommend taking into account the 10-year adjusted renal transplantation graft survival rates and the relative paucity of donors, recognizing the possibility that the patient may have to return to dialysis at some point in the future. They also reference the lack of information regarding the beneficial impact of fistula ligation on cardiac morphology and function as a rationale for access preservation.
A recent presentation at the American Heart Association Scientific Sessions by Michael B. Stokes, MD,4 from the department of cardiology at Royal Adelaide Hospital in Australia, suggests that cardiovascular disease is responsible for 40% of deaths among kidney transplant recipients and that left ventricular (LV) mass is strongly associated with cardiovascular mortality.
He states that, although there is no guideline consensus on the management of an AV fistula following successful renal transplantation, the fistula continues to contribute adversely to cardiac remodeling and function. The lack of previous randomized controlled trials in this area led Dr. Stokes and his colleagues to randomly assign 64 patients at least 1 year following successful kidney transplantation with stable renal function and a functioning AV fistula to either fistula ligation or no intervention. All patients underwent cardiac MRI at baseline and 6 months.
The primary endpoint of decrease in LV mass at 6 months was significant in the ligation group but not in the control group. The ligation group also had significant decrease in LV end diastolic volume, LV end systolic volume, and multiple other parameters. In addition, NT-proBNP levels and left atrial volume were significantly reduced in the ligation group when compared with the control group. Complications in the ligation group included six patients with thrombosis of their fistula vein and two infections, all of which resolved with outpatient anti-inflammatory or antimicrobial therapy.
Dr. Stokes believes that control patients in his study face “persisting and substantial deleterious cardiac remodeling” and that “further investigation would clarify the impact of AV fistula ligation on clinical outcomes following kidney transplantation.”
I believe this is important information and represents the first randomized controlled data regarding the long-term adverse cardiac effects of a patent fistula after renal transplantation. Unfortunately, information regarding baseline fistula volume flow is not provided in this abstract. As discussed earlier, patients with high-flow fistulas may be at increased risk of heart failure and hemodynamic data can be critical in establishing an algorithm for managing these challenging patients.
Ligation of a functioning and asymptomatic access in a patient with a successful renal transplant should be recommended only after informed discussion with the patient weighing the ongoing potential negative effects on cardiac function of continued access patency versus the potential need for future hemodialysis. Dr. Stokes presents interesting data that must be considered in this controversy. I believe that, in the absence of a universally applicable algorithm, the clinical decision to recommend AV fistula ligation after successful kidney transplantation should be individualized and based on ongoing assessment of cardiac and renal function and fistula complications and hemodynamics.
References
1. Eur Heart J 2017;38:1913-23.
2. Nephrol Dial Transplant 2008;23:282-7.
3. J Vasc Access 2012;13:405-8.
4. Stokes MB, et al. LBS.05 – Late Breaking Clinical Trial: Hot News in HF. Presented at American Heart Association Scientific Sessions. 2018 Nov 10-12. Chicago.
Larry A. Scher, MD, is a vascular surgeon at the Montefiore Greene Medical Arts Pavilion, New York, and an associate medical editor for Vascular Specialist.
Hemodynamic complications of arteriovenous (AV) access are uncommon but can be potentially life threatening. Fistulas and grafts can cause a decrease in systemic vascular resistance and secondary increase in cardiac output in patients who may already have myocardial dysfunction secondary to their end-stage renal disease.1 This increased cardiac output is usually insignificant but in rare cases can result in clinically significant cardiac failure. Patients with high-output fistulas with volume flow greater than 2 L/min may be at increased risk of heart failure but volume flow less than 2 L/min does not preclude this complication.2
In patients with AV access–related heart failure, optimal medical management and reduction of fistula flow or ligation of the dialysis access should be considered. If continued hemodialysis is necessary, loss of a functioning dialysis access is problematic and difficult management decisions must be made. Following successful renal transplantation, ligation of vascular access in the presence of symptomatic heart failure may represent a straightforward decision. Nonetheless, there is no clear consensus of how to manage patent fistulas or grafts in patients following renal transplantation in the absence of significant cardiac symptoms with particular concern to the important issues of transplant survival and long-term cardiac prognosis. Yaffe and Greenstein3 recommend preservation of almost all fistulas after transplantation in the absence of significant complications such as venous hypertension, pseudoaneurysm, significant high-output cardiac failure or hand ischemia. They recommend taking into account the 10-year adjusted renal transplantation graft survival rates and the relative paucity of donors, recognizing the possibility that the patient may have to return to dialysis at some point in the future. They also reference the lack of information regarding the beneficial impact of fistula ligation on cardiac morphology and function as a rationale for access preservation.
A recent presentation at the American Heart Association Scientific Sessions by Michael B. Stokes, MD,4 from the department of cardiology at Royal Adelaide Hospital in Australia, suggests that cardiovascular disease is responsible for 40% of deaths among kidney transplant recipients and that left ventricular (LV) mass is strongly associated with cardiovascular mortality.
He states that, although there is no guideline consensus on the management of an AV fistula following successful renal transplantation, the fistula continues to contribute adversely to cardiac remodeling and function. The lack of previous randomized controlled trials in this area led Dr. Stokes and his colleagues to randomly assign 64 patients at least 1 year following successful kidney transplantation with stable renal function and a functioning AV fistula to either fistula ligation or no intervention. All patients underwent cardiac MRI at baseline and 6 months.
The primary endpoint of decrease in LV mass at 6 months was significant in the ligation group but not in the control group. The ligation group also had significant decrease in LV end diastolic volume, LV end systolic volume, and multiple other parameters. In addition, NT-proBNP levels and left atrial volume were significantly reduced in the ligation group when compared with the control group. Complications in the ligation group included six patients with thrombosis of their fistula vein and two infections, all of which resolved with outpatient anti-inflammatory or antimicrobial therapy.
Dr. Stokes believes that control patients in his study face “persisting and substantial deleterious cardiac remodeling” and that “further investigation would clarify the impact of AV fistula ligation on clinical outcomes following kidney transplantation.”
I believe this is important information and represents the first randomized controlled data regarding the long-term adverse cardiac effects of a patent fistula after renal transplantation. Unfortunately, information regarding baseline fistula volume flow is not provided in this abstract. As discussed earlier, patients with high-flow fistulas may be at increased risk of heart failure and hemodynamic data can be critical in establishing an algorithm for managing these challenging patients.
Ligation of a functioning and asymptomatic access in a patient with a successful renal transplant should be recommended only after informed discussion with the patient weighing the ongoing potential negative effects on cardiac function of continued access patency versus the potential need for future hemodialysis. Dr. Stokes presents interesting data that must be considered in this controversy. I believe that, in the absence of a universally applicable algorithm, the clinical decision to recommend AV fistula ligation after successful kidney transplantation should be individualized and based on ongoing assessment of cardiac and renal function and fistula complications and hemodynamics.
References
1. Eur Heart J 2017;38:1913-23.
2. Nephrol Dial Transplant 2008;23:282-7.
3. J Vasc Access 2012;13:405-8.
4. Stokes MB, et al. LBS.05 – Late Breaking Clinical Trial: Hot News in HF. Presented at American Heart Association Scientific Sessions. 2018 Nov 10-12. Chicago.
Larry A. Scher, MD, is a vascular surgeon at the Montefiore Greene Medical Arts Pavilion, New York, and an associate medical editor for Vascular Specialist.
Hemodynamic complications of arteriovenous (AV) access are uncommon but can be potentially life threatening. Fistulas and grafts can cause a decrease in systemic vascular resistance and secondary increase in cardiac output in patients who may already have myocardial dysfunction secondary to their end-stage renal disease.1 This increased cardiac output is usually insignificant but in rare cases can result in clinically significant cardiac failure. Patients with high-output fistulas with volume flow greater than 2 L/min may be at increased risk of heart failure but volume flow less than 2 L/min does not preclude this complication.2
In patients with AV access–related heart failure, optimal medical management and reduction of fistula flow or ligation of the dialysis access should be considered. If continued hemodialysis is necessary, loss of a functioning dialysis access is problematic and difficult management decisions must be made. Following successful renal transplantation, ligation of vascular access in the presence of symptomatic heart failure may represent a straightforward decision. Nonetheless, there is no clear consensus of how to manage patent fistulas or grafts in patients following renal transplantation in the absence of significant cardiac symptoms with particular concern to the important issues of transplant survival and long-term cardiac prognosis. Yaffe and Greenstein3 recommend preservation of almost all fistulas after transplantation in the absence of significant complications such as venous hypertension, pseudoaneurysm, significant high-output cardiac failure or hand ischemia. They recommend taking into account the 10-year adjusted renal transplantation graft survival rates and the relative paucity of donors, recognizing the possibility that the patient may have to return to dialysis at some point in the future. They also reference the lack of information regarding the beneficial impact of fistula ligation on cardiac morphology and function as a rationale for access preservation.
A recent presentation at the American Heart Association Scientific Sessions by Michael B. Stokes, MD,4 from the department of cardiology at Royal Adelaide Hospital in Australia, suggests that cardiovascular disease is responsible for 40% of deaths among kidney transplant recipients and that left ventricular (LV) mass is strongly associated with cardiovascular mortality.
He states that, although there is no guideline consensus on the management of an AV fistula following successful renal transplantation, the fistula continues to contribute adversely to cardiac remodeling and function. The lack of previous randomized controlled trials in this area led Dr. Stokes and his colleagues to randomly assign 64 patients at least 1 year following successful kidney transplantation with stable renal function and a functioning AV fistula to either fistula ligation or no intervention. All patients underwent cardiac MRI at baseline and 6 months.
The primary endpoint of decrease in LV mass at 6 months was significant in the ligation group but not in the control group. The ligation group also had significant decrease in LV end diastolic volume, LV end systolic volume, and multiple other parameters. In addition, NT-proBNP levels and left atrial volume were significantly reduced in the ligation group when compared with the control group. Complications in the ligation group included six patients with thrombosis of their fistula vein and two infections, all of which resolved with outpatient anti-inflammatory or antimicrobial therapy.
Dr. Stokes believes that control patients in his study face “persisting and substantial deleterious cardiac remodeling” and that “further investigation would clarify the impact of AV fistula ligation on clinical outcomes following kidney transplantation.”
I believe this is important information and represents the first randomized controlled data regarding the long-term adverse cardiac effects of a patent fistula after renal transplantation. Unfortunately, information regarding baseline fistula volume flow is not provided in this abstract. As discussed earlier, patients with high-flow fistulas may be at increased risk of heart failure and hemodynamic data can be critical in establishing an algorithm for managing these challenging patients.
Ligation of a functioning and asymptomatic access in a patient with a successful renal transplant should be recommended only after informed discussion with the patient weighing the ongoing potential negative effects on cardiac function of continued access patency versus the potential need for future hemodialysis. Dr. Stokes presents interesting data that must be considered in this controversy. I believe that, in the absence of a universally applicable algorithm, the clinical decision to recommend AV fistula ligation after successful kidney transplantation should be individualized and based on ongoing assessment of cardiac and renal function and fistula complications and hemodynamics.
References
1. Eur Heart J 2017;38:1913-23.
2. Nephrol Dial Transplant 2008;23:282-7.
3. J Vasc Access 2012;13:405-8.
4. Stokes MB, et al. LBS.05 – Late Breaking Clinical Trial: Hot News in HF. Presented at American Heart Association Scientific Sessions. 2018 Nov 10-12. Chicago.
Larry A. Scher, MD, is a vascular surgeon at the Montefiore Greene Medical Arts Pavilion, New York, and an associate medical editor for Vascular Specialist.
Heart failure outcomes are worse in select HIV-infected individuals
People living with HIV (PLHIV) who have a low CD4 count or detectable viral load (VL) have an increased 30-day heart failure (HF) readmission rate as well as increased cardiovascular and all-cause mortality, compared with uninfected controls, according to Raza M. Alvi, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his colleagues.
Overall, the 30-day HF hospital readmission rate was higher among PLHIV versus non-HIV–infected individuals (49% vs. 32%, P less than .001), according to the results of their cohort study of 2,308 individuals admitted to the hospital with decompensated HF.
PLHIV and the non-HIV control groups were both followed over 2 years with a median follow-up period of 19 months, the authors wrote in the American Heart Journal. Demographic make-up of the two groups was similar; in particular, there was no difference in blood pressure and heart rate between the PLHIV and non-HIV controls, suggesting that adherence with HF medications may be similar between groups. The cohorts differed primarily in that pulmonary artery systolic pressure was significantly higher (45 vs. 40 mm Hg; P less than .001) in the HIV group, as was cocaine use (36% vs. 19%; P less than .001) and hepatitis C virus (HCV) infection (13% vs. 7%; P less than .001).
The differing results between the two cohorts were primarily caused by the fact that, for PLHIV with HF, CD4 count and VL were risk factors for adverse outcomes among patients with all types of HF. (30-day HF readmission, cardiovascular [CV] mortality, and all-cause mortality), compared with those with CD4 count greater than or equal to 200 cells/mm3. In addition, a low CD4 count/high VL independently related to an increased 30-day HF readmission rate even after the researchers controlled for major traditional and nontraditional HF risk factors.
“Rates of 30-day HF readmission, CV mortality, and all-cause mortality are worse among individuals with a low CD4 count or nonsuppressed viral load,” the researchers concluded.
The National Institutes of Health sponsored the study. The authors reported that they had no conflicts.
SOURCE: Alvi RM et al. Am Heart J. 2019 Apr;210:39-48.
People living with HIV (PLHIV) who have a low CD4 count or detectable viral load (VL) have an increased 30-day heart failure (HF) readmission rate as well as increased cardiovascular and all-cause mortality, compared with uninfected controls, according to Raza M. Alvi, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his colleagues.
Overall, the 30-day HF hospital readmission rate was higher among PLHIV versus non-HIV–infected individuals (49% vs. 32%, P less than .001), according to the results of their cohort study of 2,308 individuals admitted to the hospital with decompensated HF.
PLHIV and the non-HIV control groups were both followed over 2 years with a median follow-up period of 19 months, the authors wrote in the American Heart Journal. Demographic make-up of the two groups was similar; in particular, there was no difference in blood pressure and heart rate between the PLHIV and non-HIV controls, suggesting that adherence with HF medications may be similar between groups. The cohorts differed primarily in that pulmonary artery systolic pressure was significantly higher (45 vs. 40 mm Hg; P less than .001) in the HIV group, as was cocaine use (36% vs. 19%; P less than .001) and hepatitis C virus (HCV) infection (13% vs. 7%; P less than .001).
The differing results between the two cohorts were primarily caused by the fact that, for PLHIV with HF, CD4 count and VL were risk factors for adverse outcomes among patients with all types of HF. (30-day HF readmission, cardiovascular [CV] mortality, and all-cause mortality), compared with those with CD4 count greater than or equal to 200 cells/mm3. In addition, a low CD4 count/high VL independently related to an increased 30-day HF readmission rate even after the researchers controlled for major traditional and nontraditional HF risk factors.
“Rates of 30-day HF readmission, CV mortality, and all-cause mortality are worse among individuals with a low CD4 count or nonsuppressed viral load,” the researchers concluded.
The National Institutes of Health sponsored the study. The authors reported that they had no conflicts.
SOURCE: Alvi RM et al. Am Heart J. 2019 Apr;210:39-48.
People living with HIV (PLHIV) who have a low CD4 count or detectable viral load (VL) have an increased 30-day heart failure (HF) readmission rate as well as increased cardiovascular and all-cause mortality, compared with uninfected controls, according to Raza M. Alvi, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his colleagues.
Overall, the 30-day HF hospital readmission rate was higher among PLHIV versus non-HIV–infected individuals (49% vs. 32%, P less than .001), according to the results of their cohort study of 2,308 individuals admitted to the hospital with decompensated HF.
PLHIV and the non-HIV control groups were both followed over 2 years with a median follow-up period of 19 months, the authors wrote in the American Heart Journal. Demographic make-up of the two groups was similar; in particular, there was no difference in blood pressure and heart rate between the PLHIV and non-HIV controls, suggesting that adherence with HF medications may be similar between groups. The cohorts differed primarily in that pulmonary artery systolic pressure was significantly higher (45 vs. 40 mm Hg; P less than .001) in the HIV group, as was cocaine use (36% vs. 19%; P less than .001) and hepatitis C virus (HCV) infection (13% vs. 7%; P less than .001).
The differing results between the two cohorts were primarily caused by the fact that, for PLHIV with HF, CD4 count and VL were risk factors for adverse outcomes among patients with all types of HF. (30-day HF readmission, cardiovascular [CV] mortality, and all-cause mortality), compared with those with CD4 count greater than or equal to 200 cells/mm3. In addition, a low CD4 count/high VL independently related to an increased 30-day HF readmission rate even after the researchers controlled for major traditional and nontraditional HF risk factors.
“Rates of 30-day HF readmission, CV mortality, and all-cause mortality are worse among individuals with a low CD4 count or nonsuppressed viral load,” the researchers concluded.
The National Institutes of Health sponsored the study. The authors reported that they had no conflicts.
SOURCE: Alvi RM et al. Am Heart J. 2019 Apr;210:39-48.
FROM THE AMERICAN HEART JOURNAL