Study Shows Aortic Valve Replacement Was Associated With Better Outcomes in Patients with Low-Gradient Aortic Stenosis and Preserved Left Ventricular Ejection Fraction Compared With High-Gradient Aortic Stenosis Analysis of PARTNER 2A randomized trial and SAPIEN 3 registry

A recent study by Dr. Salaun, published in Circulation: Cardiovascular Interventions, demonstrated that aortic valve replacement in patients with the low gradient (LG, defined as mean gradient <40 mmHg) severe aortic stenosis (AS) and preserved ejection fraction (EF) has resulted in better outcomes versus in those with the high gradient (HG, defined as a mean transvalvular gradient (MG) 40 mmHg) AS. Also, the study revealed that patients with classical low flow, low gradient (CLF-LG, defined as MG <40 mmHg and LVEF <50%) AS were at higher risk of death, rehospitalization, or stroke at 2 years.

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DAPA-HF Trial: Compared to Placebo, Dapagliflozin Was Beneficial in Patients with Heart Failure and Reduced Ejection Fraction Regardless of Background Diuretic Therapy

A recent study by Dr. Alice M. Jackson M.D., published in Circulation journal, showed that the use of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with reduced ejection fraction heart failure (HF) is associated with reduced risk of cardiovascular (CV) death or a worsening HF event, and all-cause death. These effects remained consistent among different subgroups of diuretic therapy. 
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Integrated Management of Atrial Fibrillation in Primary Care Demonstrates 45% Reduction in All-Cause Mortality Compared to Usual Care in Elderly Patients

In a recent Dutch study, published in European Heart Journalintegrated care for elderly atrial fibrillation (AF) patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.

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Cohort Study Showed a Large Number of Patients Receiving Anticancer Therapy Demonstrate Myocardial Injury or Left Ventricular Dysfunction, With Only Few Showing Severe Cardiotoxicity

A recent study by Dr. Lopez-Sendon, published in European Heart Journal, showed that cardiotoxicity in the form of left ventricular dysfunction or myocardial injury affects a large portion of patients receiving high-risk anticancer therapy with only severe form strongly associated with all-cause mortality.

Cardiotoxicity has been known as one of the major side effects of anti-cancer therapy that may present with left ventricular dysfunction and heart failure. Given that the early recognition and treatment of these side effects have been associated with a higher recovery rate, a united diagnostic and management guideline seems necessary.

The CARDIOTOX (CARDIOvascular TOXicity induced by cancer-related therapies) registry has been established to determine the prevalence of cardiotoxicity markers as well as their association with guideline-based heart failure criteria and treatment in patients receiving chemotherapeutic agents. To achieve this purpose, a total of 865 patients receiving anticancer regimens associated with moderate to high cardiotoxicity were selected and followed for a median of 24 months. Clinical data, blood samples, and echocardiographic features were collected before the initiation of anticancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years afterward. Patients with past or current history of heart failure or reduced left ventricular ejection fraction (< 40%) and those with a history of previous cancer therapy including chemotherapy and radiation therapy were excluded from the study. Cardiotoxicity was defined as any new deterioration from the baseline of myocardial/ventricular function during follow-up periods. Cardiotoxicity was also sub-classified into four stages depending on the worst myocardial dysfunction/injury observed in the follow-up period. Myocardial dysfunction/injury stages include the following: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥ 50%; moderate, LVD with LVEF 40–49%; and severe, LVD with LVEF ≤ 40% or symptomatic heart failure.

The study indicated a high incidence (37.5%) of ventricular dysfunction among the patients, of whom only 3.1% were classified as having severe dysfunction and the majority have been classified as mild (31.6%). All-cause mortality was also observed to be higher among those with severe cardiotoxicity than other groups. According to the author, the relatively low prevalence of severe cardiotoxicity in the study population was due to the exclusion of patients with a previous history of cardiac dysfunction and the improvement in the follow-up of the cancer patients in the context of cardio-oncology service. Severe cardiotoxicity has also been associated with a 10-fold increase in total mortality compared to a less severe form of cardiotoxicity. A classification of cardiotoxicity using current heart failure guidelines is also proposed by the authors for future studies. This study acknowledged the critical role of comprehensive monitoring and follow-up for the development of cardiovascular symptoms and left ventricular dysfunction in patients receiving chemotherapeutic agents with potential cardiotoxicity.

Limitations that are worthy of mentioning include the inclusion of patients with some degree of abnormality in biomarkers and echocardiographic findings at baseline. Secondly, the prevalence of myocardial damage may be underestimated due to a number of missing visits or incomplete data collection during the follow-up period. Future research is warranted to approve the relationship of different stages of cardiotoxicity with clinical outcomes.

Study Shows Hepatitis C Status Not Associated With Adverse Events in Adult Heart Transplant Patients by 1 Year

A recent study by Dr. Kilic, published in the American Heart Association Journal, showed similar adverse outcomes in the 1-year survival, rejection rates, and complications of patients who received a heart transplant using hepatitis C-positive (HCV+) donors whereas those using hepatitis C-negative donors.

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Elevated Coronary Sinus Neuropeptide Y Levels Are Associated With Adverse Outcomes in Patients With Chronic Heart Failure

The study by Dr. Ajijola, published in JAMA Cardiology, found that elevated coronary sinus neuropeptide Y (NPY) level is associated with adverse cardiovascular events in stable patients with chronic heart failure and therefore, it may have prognostic value in this population.

Increased cardiac sympathetic signaling has been associated with adverse cardiovascular outcomes. Biomarkers of the sympathetic system are of significant interest in the assessment of cardiovascular outcomes. NPY is one of the circulating catecholamines, which may predict the risk of death in patients with chronic heart failure.

Dr. Ajijola and his colleagues conducted a prospective observational cohort study at a single-center, tertiary care hospital. They observed 105 patients with stable heart failure undergoing elective cardiac resynchronization therapy (CRT) device implantation between 2013 and 2015. Patients with NYHA class I, severe aortic stenosis, cardiac surgery within prior 90 days, severe obstructive pulmonary disease requiring oxygen or with recent decompensation (< 30 days), current pregnancy, primary pulmonary hypertension, continuous intravenous drug infusion for heart failure, and life expectancy under 6 months were excluded from the study. At the time of the intervention, the coronary sinus blood sample was taken and checked for the NPY levels. Patients were evaluated for major adverse cardiovascular events (MACE) as well as responses to CRT.  Composite endpoint was defined as death, cardiac transplant (OHT), or ventricular assist device (VAD) placement.

The results of the study showed that NPY levels of coronary sinus were associated with prognostic implications in patients with heart failure. 20 out of 105 (19%) patients showed composite endpoints at a median follow-up of 29 months. Also, the NPY levels of greater than 130 pg/mL were associated with worse outcomes compared with those with lower levels (HR, 8.9; 95% CI, 3.1 – 25.7; P < 0.001). The results remained significant even after adjusting for age, eGFR, and LVEF (HR, 9.5; 95% CI, 2.92 – 30.5; P < 0.001).  According to Dr. Ajijola, “Coronary sinus NPY levels may identify patients in whom close clinical monitoring and more aggressive interventions are needed to prevent adverse events. It may also identify those in whom CRT is likely to be ineffective, and such patients may be considered sooner for OHT or VAD.”

This study is limited by some points. First, although NPY levels were irrespective of CRT response, the presence of CRT devices limits the external validity of the study. Second, the sample size was small for formal statistical validation of the study including the NPY thresholds. Future studies are warranted to further validate the results of this study and to clarify the prognostic value of NPY levels.

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.