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

Worse Clinical Outcomes of Atrial Fibrillation in Patients with HFpEF Compared to HFrEF Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry

A multinational prospective cohort study performed by Barak Zafrir et al. and published in the European Heart Journal concluded that worse cardiovascular outcomes of atrial fibrillation (AF) were associated with heart failure with preserved ejection fraction (HFpEF) and heart failure with middle range ejection fraction (HFmrEF) but not associated with heart failure with reduced ejection fraction (HFrEF). Continue reading

SGLT-2 Inhibitors Associated with Lower Heart Failure Hospitalization Tighter glycemic control is not associated with lower risk of HF hospitalization: A Meta-Analysis

A new meta-analysis published in the Journal of American College of Cardiology showed that sodium glucose co-transporter (SGLT)-2 inhibitors are more effective than glucagon-like peptide (GLP)-1 agonists and dipeptidyl peptidase (DPP)-4 inhibitors in reducing the risk of Heart Failure (HF) hospitalization in patients with type 2 diabetes mellitus. Continue reading

Pulmonary Artery Denervation Improves Pulmonary HTN in Heart Failure Pulmonary Artery Denervation Significantly Increases 6-minute Walk Distance for Patients with Combined Pre- and Post-capillary Pulmonary Hypertension Associated with the Left Heart Failure: PADN-5 Study

The findings of the Pulmonary artery denervation (PADN) trial, presented at the TCT conference on Sept 23rd have shown that PADN is associated with significant improvements in hemodynamic and clinical outcomes including 6-minute walk distance (6MWD) and pulmonary vascular resistance (PVR) in patients with combined pre- and post-capillary pulmonary hypertension CpcPH. The results of this study were simultaneously published in JACC: Interventions. Continue reading

Landmark COAPT trial Demonstrates the Benefit of Transcatheter Mitral-Valve Repair Using MitraClip in Patients with Heart Failure TCT 2018: Findings of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial

The spectacular results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial, presented at TCT 2018, show that transcatheter mitral valve approximation using the MitraClip, on a background of maximally tolerated guideline-directed medical therapy (GDMT) was superior to GDMT alone in the reduction of Heart Failure (HF) hospitalization and mortality in symptomatic HF patients with grade 3-4+ Mitral regurgitation (MR). These landmark findings were simultaneously published today in the New England Journal of Medicine. Continue reading

Coronary Microvascular Dysfunction: A Promising Therapeutic Target in Heart Failure with Preserved EF? PROMIS-HFpEF: Results from ESC 2018

PROMIS-HFpEF (PRevalence Of MIcrovascular dySfunction in Heart Failure with Preserved Ejection Fraction) is an echocardiographic trial showcasing a high prevalence of coronary microvascular dysfunction (CMD) in HFpEF and its association with systemic endothelial dysfunction (RHI, UACR) and markers of HF severity (NT-proBNP and RV dysfunction). The results of the trial were recently published in the European Heart Journal. Continue reading

Transcatheter Interatrial shunt device appears safe at 1 year for heart failure with preserved ejection fraction ESC 2018: REDUCE LAP HF-1, 1 year results from phase 2

The 1-year results of a phase 2, sham-controlled RCT have confirmed the safety of a transcatheter interatrial shunt device (IASD; Corvia Medical) with no significant cardiovascular or renal events as compared to those receiving sham control treatment. It has also confirmed the long-term patency of the device. The findings were presented at the ESC and have also been simultaneously published in JAMA Cardiology. Continue reading

Pre-PCI Impella Device Improves Outcome in Acute MI complicated by Cardiogenic Shock (AMICS)

A non-randomized study published in the American Heart Journal showed increased survival rates in patients with Impella device being used as the first support strategy for patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) when invasive hemodynamic monitoring was used, and at centers with higher Impella implantation volume. Continue reading

Tafamidis, A Real Hope for People with Transthyretin Cardiomyopathy?

On Thursday, March 29th, Pfizer announced positive topline results from ATTR-ACT trial of tafamidis in patients with transthyretin cardiomyopathy. According to Pfizer, “Tafamidis met its primary endpoint, demonstrating a statistically significant reduction in the composite of all-cause mortality and frequency of cardiovascular-related hospitalizations compared to placebo at 30 months. The preliminary safety data showed that tafamidis was generally well tolerated in this population and no new safety signals were identified”. Continue reading

Association of High-Sensitivity Cardiac Troponins (hs-cTn) and the Risk of New-onset Heart Failure

A recent study, published in the Journal of American College of Cardiology, concluded that there is a strong association of high sensitivity cardiac troponin (hs-cTn) with the risk of new-onset heart failure (HF), independent of population at risk, cardiovascular risk factors, and natriuretic peptide levels. Continue reading

ICON RELOADED: A New Future for NT-proBNP

A multicenter, international, North American study published in the Journal of the American College of Cardiology has indicated that N-terminal pro–B-type natriuretic peptide (NT-proBNP) testing may be valuable in the identification or exclusion of heart failure in emergency department patients with shortness of breath.

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