The Sarcomeric Human Cardiomyopathy Registry: Race Associated with Disease Expression and Clinical Outcomes Among Patients with Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy and race: differences in disease expression, inequitable care provision, and disparate clinical outcomes

Hypertrophic cardiomyopathy (HCM) is the most common inherited genetic disorder of the myocardium, and the number one culprit of sudden cardiac death in athletes, particularly African Americans.

“Is race associated with differential disease expression, inequitable care provision, or disparate clinical outcomes among patients with hypertrophic cardiomyopathy?”

In order to answer the above question, Lauren A. Eberly, et al. studied 2,467 patients with hypertrophic cardiomyopathy. In a retrospective cohort study, black and white patients with hypertrophic cardiomyopathy from the US-based sites of the Sarcomeric Human Cardiomyopathy Registry from 1989 through 2018 compared in terms of baseline characteristics; genetic architecture; adverse outcomes such as cardiac arrest, cardiac transplantation or left ventricular assist device implantation, cardioverter-defibrillator implantation, all-cause mortality, atrial fibrillation, stroke,  prevalence and likelihood of developing heart failure; and receiving septal reduction therapies.

According to the results of this study (8.3 percent black; 91.7 percent white), published in the JAMA CARDIOLOGY (December 2019), compared with white patients, black patients with HCM were younger (mean age, 36.5 versus 41.9 years), were less likely to have sarcomere mutations (26.1 versus 40.5 percent), had a higher prevalence of New York Heart Association (NYHA) class III or IV heart failure at presentation (22.6 versus 15.8 percent) and were more prone to developing heart failure (hazard ratio, 1.45). Lower rates of genetic testing (26.1 versus 40.5 percent) have been observed in black patients. Although there were no racial differences in implantation of implantable cardioverter-defibrillators, the invasive septal reduction was less common among African Americans (14.6 versus 23 percent). Nevertheless, Black patients had fewer incidents of atrial fibrillation (35 [17.1 percent] versus 608 [26.9 percent].

The results of this study were in accordance with the previous studies that mentioned a higher prevalence of complicated hypertrophic cardiomyopathy in African Americans in contrast to the lower prevalence of HCM in this community.  Eberly, et al. believe that racial differences in disease expression and adverse clinical outcomes are not only because of different characteristics of the disease in African Americans but also inequities in clinical care provision might be responsible for these observed differences.

Nationwide Study Shows New-onset Left Bundle Branch Block After Transcatheter Aortic Valve Replacement Occurred in 15% of Intermediate Risk Patients and Is Associated with Worse 2 Year Outcomes

According to a new nationwide study,  new onset left bundle branch block (LBBB) post transcatheter aortic valve replacement (TAVR), a recently established therapy for intermediate risk surgical candidates with symptomatic, severe aortic stenosis, is associated with adverse long term clinical outcomes in patients without baseline conduction disturbances or pacemaker.  Based on the findings published in the European Heart Journal, these outcomes include cardiovascular mortality, re-hospitalization, new pacemaker implantation, and worsened left ventricular systolic function in intermediate risk patients.

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Meta-analysis Shows Vitamin D Supplementation Does Not Improve Cardiovascular Outcomes

In the largest updated meta-analysis study conducted to understand the inverse association between low serum vitamin D supplementation and increased cardiovascular disease (CVD) risks, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality) or all-cause mortality.  The findings published in the Journal of the American Medical Association Cardiology suggest vitamin D supplementation may not confer cardiovascular protection and may not be indicated for this purpose. Continue reading

New 22 Year Follow Up Study Shows Bariatric Surgery Associated with Lower Risk of Heart Failure in Obese Patients

In a study published in the European Heart Journal, Dr. Shabbar Jamaly and his team showed that in patients with obesity and no history of heart failure, being treated with bariatric surgery was associated with a reduced risk of heart failure.

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A 5% Absolute Increase in Influenza Activity Associated with a 24% Increase in Heart Failure Hospitalizations, According to New Study The Atherosclerosis Risk in Communities Study

A study conducted by Sonja Kytömaa and Sheila Hegde of the cardiovascular division, Brigham and Women’s Hospital, Boston, Massachusetts, reported that influenza activity was temporally associated with an increase in HF hospitalizations across 4 influenza seasons. According to the publication in JAMA Cardiology, these data suggested that influenza could contribute to the risk of HF hospitalization in the general population. Continue reading

Dapagliflozin and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Prior MI ACC 2019: A Sub-analysis From DECLARE TIMI-58 Trial

According to a presentation by Dr. Marc P. Bonaca at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA on March 18, 2019, patients with type 2 diabetes mellitus (T2DM) and prior MI are at high risk of major adverse cardiovascular events (MACE) and cardiovascular (CV) death/HHF. Dapagliflozin appears to robustly reduce the risk of both composite outcomes in these patients. These results were published online in Circulation. Continue reading

HeartMate3 Found to be More Superior Than Other LVADs on Endpoints of Stroke, Pump Thrombosis and Bleeding Complications ACC 2019: A Fully Magnetically Levitated Left Ventricular Assist Device — Final Report

The largest LVAD trial ever to be performed, led by Dr. Mandeep Mehra published the final analysis of a fully magnetically levitated left ventricular assist device in the New England Journal of Medicine. According to this, among patients with advanced heart failure, a fully magnetically levitated centrifugal- flow pump has been found to be superior to a mechanical-bearing axial-flow pump in advanced heart failure patients in terms of survival free of disabling stroke or reoperation for removal in case of device malfunction. Continue reading

Findings From a Randomized Controlled Trial May Usher the Adoption of Angiotensin–Neprilysin Inhibition to the Heart-Failure Armamentarium Presented At the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA.

The results of a trial presented by Dr. Adam DeVore at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, reflected that among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration as compared with enalapril therapy. In addition to this, the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two arms. Continue reading

U.S. Food and Drug Administration (FDA) Continues To Investigate Recall of Contaminated Blood Pressure Medication Potentially carcinogenic nitrosamine impurities found in angiotensin receptor blockers (ARBs)

The US food and drug Administration (FDA) has recently been conducting an investigation on voluntary recalls of multiple generic angiotensin II receptor blocker (ARB) drug products used to treat high blood pressure and heart failure. The recalls initiated in July 2018 and continue to date due to the presence of Nitrosamine impurities, including N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA), which are potential human carcinogens in different ARB products. Last week, AurobindoPharma USA notified that it is expanding its recall to include 38 more lots of valsartan and amlodipine/valsartan tablets due to objectionable levels of N-Nitrosodiethylamine (NDEA). This was later followed by an expanded voluntary recall of losartan potassium produced by Hetero Labs (India) when they were found to be contaminated by N-Nitroso-N-methyl-4-aminobutyric acid (NMBA). Camber Pharmaceuticals called back 87 lots of losartan potassium tablets (25 mg, 50 mg and 100 mg), 114 lots of losartan potassium or losartan potassium/hydrochlorothiazide tablets, and one lot of losartan potassium/hydrochlorothiazide tablets. Continue reading

Did the Hospital Readmissions Reduction Program Impact Heart Failure Readmission or Mortality? Comparison of the change in heart failure readmission and mortality rates between hospitals subject to hospital readmission reduction program penalties and critical access hospitals

An article by Sandhu et al. published in the American Heart Journal reported that on using critical access hospitals (CAHs) as a control group, the introduction of financial penalties was only associated with modest reductions in readmissions and an uncertain association with mortality. Continue reading

CHIPping Away at the Pathogenesis of Chronic Heart Failure: What is the Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential (CHIP)? Association of Mutations Contributing to Clonal Hematopoiesis With Prognosis in Chronic Ischemic Heart Failure

In a study published in JAMA cardiology, the data suggested that somatic mutations in hematopoietic cells, specifically in the most commonly mutated CHIP driver genes TET2 and DNMT3A, could be significantly associated with the progression and poor prognosis of CHF. The study was led by Dr. Lena Dorsheimer from the Department of Medicine, Goethe University Hospital, Frankfurt, Germany. Continue reading

2018: Cardiology News at A Glance Most important trials published in 2018

COAPT trial

This prospective, multicenter, open-label, randomized trial aimed to assess the use of transcatheter mitral valve repair in heart failure (HF) patients with mitral regurgitation due to left ventricular dysfunction. A total of 614 patients were randomized to either receiving guideline-directed medical therapy (GDMT) alone or GDMT in addition to transcatheter mitral-valve repair. The primary efficacy endpoint was all hospitalizations due to heart failure at 24 months of follow-up, while the primary safety endpoint was freedom from device-related complications at 12 months of follow-up. The study showed that the device group had a lower risk of hospitalization for HF (HR 0.53, 95% CI 0.4-0.7) and all-cause mortality (HR 0.62, 95% CI 0.46-0.82) at 24 months. Moreover, the rate of freedom from device complications at 12 months was 96.6% which exceeded the prespecified safety threshold. Continue reading

Flu Shot Linked to Heart Failure Survival Influenza Vaccine in Heart Failure: Cumulative Number of Vaccinations, Frequency, Timing, and Survival: A Danish Nationwide Cohort Study

Patients with heart failure (HF) who receive influenza vaccination may be at a lower risk of both all-cause mortality and cardiovascular death after adjustment for confounders, according to a large-scale observational nationwide study of Danish citizens. “Annual influenza vaccination may be an effective treatment strategy to improve survival in heart failure,” lead author Daniel Modin (Department of Cardiology, Herlev & Gentofte Hospital, Denmark), and colleagues wrote in their paper recently published in Circulation. Continue reading

NT-ProBNP-Guided Medical Therapy Failed To Show Superiority Compared To Usual Care In HFrEF Results from the GUIDE-IT trial

Results of a multi-center, randomized clinical trial which enrolled 894 patients with heart failure (HF) with reduced ejection fraction (EF ≤40%) published in the most recent issue of the Journal of the American College of Cardiology (JACC) have shown that management, using NT-ProBNP-guided optimal medical therapy, has higher total costs and fails to show superior efficacy in improving quality of life (QoL) outcomes compared to usual care (titration of guideline-recommended therapy to doses established in pivotal clinical trials).

The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial planned to prospectively enroll 1100 patients from 45 clinical sites in the United States and Canada. After a scheduled review by the DSMB, the study was stopped for lack of efficacy of the biomarker-guided strategy. The patients included in the study presented with chronic HF and an EF of ≤40%; these subjects were randomly assigned in a 1:1 fashion to an NT-proBNP-guided treatment strategy (n=446) or usual care (n=448). Patients in the NT-proBNP- guided strategy received medical therapy with a goal of achieving a NT-proBNP level <1000 pg/ml. Structured evaluations performed at baseline and 3, 6, 12, and 24 months post-randomization were employed to collect and compare data on quality of life (QoL). The Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI) were used to stratify pre-specified QoL measures. In addition, researchers examined the costs associated with either treatment strategy in 735 US patients. The results showed that both the KCCQ and the DASI improved over the first 6 months ( 11-point improvement in the 4 KCCQ composite scales which included physical limitations, total symptoms, QoL, and social limitations), but no evidence was found for a strategy-related difference (mean difference [biomarker-guided usual care] at 24 months of follow-up, 2.0 for DASI [95% confidence interval (CI): 1.3 to 5.3] and 1.1 for KCCQ [95% CI: 3.7 to 5.9]). Albeit the lack of strategy-related difference, both treatment arms did show improvements in KCCQ and DASI scores overall. Total winsorized costs (to reduce the effect of possibly false outliers) averaged $5,919 higher in the biomarker-guided strategy (95% CI: $1,795 + $13,602) over 15-month median follow-up.

“The big message from GUIDE-IT, or a big message from GUIDE-IT, is that, regardless of which arm you ran patients on or who got treated more aggressively, when we were able to get their NT-proBNP levels down, the lower did better regardless of which treatment arm they were in.” – G. Michael Felker, MD, MHS (Duke University Medical Center)

Previous trials have revealed various effective management strategies for HF patients that lead to symptomatic relief (primarily dyspnea) and improve prognosis but other major symptoms such as fatigue and exercise intolerance have not been well correlated with either central measures of cardiac performance or measures of patient-reported QoL. Indeed, most of the clinical trials of effective medical therapies in HF that included QoL measurement showed small or no changes in QoL. NT‐proBNP has emerged as a powerful biomarker in various cardiovascular diseases and serves to provide strong and independent prognostic information in patients with heart failure. The investigators of the GUIDE-IT trial aimed to study whether the attempt to achieve a sufficiently low NT-proBNP level would affect QoL either beneficially or adversely. The investigators concluded that they found no evidence of a QoL effect associated with randomization to the strategy of NT-proBNP– guided therapy. In 735 patients enrolled in the United States, medical costs were increased in the biomarker-guided arm, primarily due to extra hospital-based care.

The limitations of the study included early termination with less follow-up time than was planned for in the trial design, secondly the unblinded nature of the analyses may have contributed to the lack of benefit seen in the biomarker-guided arm. Thirdly, both groups had more frequent medical contacts related to study participation compared to standard of care.

Mechanistic Study Delves Into Heart Failure Benefits Noted With Empagliflozin EMPA-HEART Cardiolink-6 - EMPA-HEART

The EMPA-HEART trial showed that empagliflozin resulted in beneficial effects on left ventricular remodeling at 6 months among patients with type 2 diabetes mellitus and stable coronary artery disease (CAD) but normal ejection fraction and without a clear heart failure history. The findings were presented by Dr. Subodh Verma at the American Heart Association Annual Scientific Sessions (AHA 2018) in Chicago, Illinois. Continue reading

TRED-HF: Tread With Caution While Withdrawing Heart Failure Medication in Recovered Dilated Cardiomyopathy Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy: an open-label, pilot, randomised trial

The results of the TRED-HF trial published in The Lancet showed that withdrawal of heart failure medications among patients with dilated cardiomyopathy (DCM) who had recovered their LV function resulted in the relapse of HF. According to Halliday and his colleagues, until robust predictors of relapse are defined, treatment should continue indefinitely. Continue reading

Canakinumab: A New Hope for Post MI Patients with Increased hsCRP in the Prevention of Heart Failure The exploratory analysis of the CANTOS trial showed that canakinumab can decrease hear failure hospitalizations in ischemic patients in a dose-dependent manner

Canakinumab (an IL-B inhibitor) is associated with decreased heart failure (HF) hospitalizations and the composite of heart failure hospitalization and heart-failure related mortality in patients with a history of myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hsCRP), according to a new study published in Circulation. Continue reading

Superior Efficacy of Sacubitril-Valsartan Compared to Enalapril for lowering NT Pro-BNP in Patients Hospitalized for HFrEF Pioneering a new strategy for managing acute decompensation in HFrEF (Results from the PIONEER-HF trial)

Results from a multi-center, randomized, double-blind, double dummy, parallel group clinical trial which enrolled 881 patients with heart failure (HF) with reduced ejection fraction (HFrEF-left ventricular ejection fraction of 40% or less) have shown superior efficacy of Sacubitril–Valsartan combination (Entresto; Novartis) in reducing N-terminal pro-B-type natriuretic peptide compared to Enalapril alone. The patients were hospitalized for acute decompensation of HF, and treatment with Sacubitril–Valsartan achieved a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations without any significant offsetting serious adverse events. Findings from the trial were presented at the 2018 AHA Scientific Session and simultaneously published in the New England Journal of Medicine (NEJM). Continue reading

Does a Low Salt Diet Improve Heart Failure Prognosis? Reduced Salt Intake for Heart Failure: A Systematic Review

A systematic review conducted by Kamal R. Mahtani et al in JAMA looked into the evidence of salt restriction recommendation on heart failure prognosis. The investigators evaluated previous trials but could not find a conclusive relationship between salt consumption and heart failure prognosis. Continue reading

Cardiogenic Shock in Takotsubo Syndrome: Incidence, Predictors, and Outcomes Results from the RETAKO registery

Cardiogenic shock (CS) is not a rare complication in patients with Takotsubo syndrome (TTS). Moreover, it is associated with an increased risk of adverse outcomes in the short- and long-term follow-up, according to a new study published in the Journal of the American College of Cardiology. Continue reading