Heart Failure With Reduced Ejection Fraction

RECOVER HF is a clinical study designed to evaluate the safety and efficacy of Synchronized Diaphragmatic Stimulation delivered using the VisONE System in the treatment of patients with heart failure.

The aim of this study is to evaluate, in adults with HFrEF in Sri Lanka, the effects of an HFrEF polypill implementation strategy on the composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations, compared with usual care over a minimum of 12-months of follow-up. Primary outcome of the study: 1\) Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration Secondary outcomes of the study: 1. Rate of cardiovascular disease mortality over study duration 2. Rate of recurrent heart failure hospitalizations over the study duration 3. Rate of all-cause mortality over the study duration 4. Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram 5. Change in BNP levels at 12 months and end of study 6. Change in overall and domain specific health-related quality of life at 12-months and end of study assessed by a translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) 7. Change in physician-reported New York Heart Association class at 12-months and end of study 8. Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire at baseline, 1-, 6-, 12-months, and end of study. Persistence assessed as continuation of assigned therapy at each follow-up visit. Dose optimization assessed as proportion achieving target doses (Strength 3 of the polypill, or comparable individual GDMT doses in the comparator arm) at 6-, 12-months, and end of study. Safety outcomes: 1. Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration 2. Proportion of participants with adverse events of special interest over study duration 3. Proportion of participants with adverse events leading to HF drug discontinuation over study duration 4. Mean change from baseline to 12-months and end of study in serum potassium (mEq/L) 5. Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL) Participants will be randomly assigned 1:1 stratified by sex and site to one of two groups, intervention (experimental arm) or usual care (control arm). The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options. Both groups will be observed over a minimum of 12-months of follow-up to assess key outcomes.

The goal of this clinical study is to evaluate the safety and efficacy of percutaneous pulmonary artery denervation with the Multi-Pole Pulmonary Artery Radiofrequency Ablation Enhancor System in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) associated with left heart disease (LHD). This randomized control trial will compare the investigational device (The Enhancor System) to control (medical therapy.) Participants who will consist of patients with chronic heart failure (HF) who are receiving maximally tolerated guideline-directed medical therapy (GDMT) for left heart failure, are clinically stable, and who have been diagnosed with CpcPH by right heart catheterization (RHC), will be treated with PADN and followed for 3 years.

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of HJB647 at two different doses in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).

Heart failure reduces the amount of blood the heart pumps, which can lead to memory and thinking problems in many patients. One possible reason is that heart failure triggers brain inflammation, a process in which certain brain immune cells (called microglia) become overactive. A heart failure medication called sacubitril-valsartan has been shown to reduce the risk of developing dementia, but it is not known whether this is because it reduces brain inflammation. This study uses a new experimental brain scan drug called \[11C\]PS13 (PS13) to measure brain inflammation directly and non-invasively, using a technique called positron emission tomography (PET). PS13 sticks to a molecule called COX-1, which is found mainly in brain immune cells (microglia). By measuring how much PS13 accumulates in the brain, researchers can estimate how much brain inflammation is present. In this pilot study, 18 patients with heart failure and mild memory or thinking problems who are being started on sacubitril-valsartan by their cardiologist (as standard clinical care) will undergo two brain PET scans: one before starting sacubitril-valsartan, and one approximately 12 weeks after. The study will also assess memory, thinking, daily function, mood, and social well-being using standard questionnaires. The study will test whether sacubitril-valsartan is associated with measurable changes in brain inflammation, and whether this type of imaging is feasible in heart failure patients. The study is funded by the American Heart Association and the National Institute on Aging, and an independent Data and Safety Monitoring Board oversees participant safety. The results will be used to design a larger study.

This prospective observational study aims to evaluate intermediate clinical, renal, and functional outcomes in patients with heart failure with reduced ejection fraction treated with contemporary guideline-directed medical therapy over a 6 to 12 month follow-up period.

The purpose of this study is to find out if the investigational drug called omecamtiv mecarbil can reduce the risk of the effects of heart failure, like hospitalization, transplantation, or death in patients with heart failure and severely reduced ejection fraction.

The purpose of the study is to implement point of care ultrasound (POCUS) to generate preliminary, or pilot, data to support a full future POCUS study across multiple Corewell Health outpatient rural facilities. The study aims to demonstrate feasibility of the procedure utilizing input from the patient, provider, and the clinic staff. Preliminary data will also be used to estimate the magnitude of effect in estimating sample size and power in participants who receive the POCUS procedure versus those who continue with standard of care. Up to 100 participants will be enrolled.

The clinical study compares the benefits of yoga based rehabilitation programme versus an educational package during recovery of patients with heart failure. Cardiac rehabilitation programmes help patients with cardiac illness to return as quickly as possible to full and productive life and to reduce the chances of further cardiac illness or death. We want to know whether our package of yoga classes can provide effective cardiac rehabilitation and how that compares with a package of educational classes. Both packages are especially designed by us to improve heart health

The evidence-based pharmacologic treatments available for patients with heart failure with reduced ejection fraction (HFrEF) has been established over the last few decades of cardiovascular research. These treatments, termed Foundational Guideline-Directed-Medical Therapies (GDMT), prolong patient life, improve patient-reported symptoms, and reduce hospitalizations for heart failure. A direct effect of most medication classes encompassed within GDMT is the reduction in blood pressure due to their mechanisms of action. In addition, as patients with HFrEF become more advanced in their disease, a significant proportion develop hypotension related to pump failure and autonomic dysfunction, amongst other possible mechanisms. As a result, a significant proportion of HFrEF patients are not optimized on GDMT with hypotension as their limiting barrier that would otherwise have served to improve their heart function, heart failure symptoms, and mortality. Currently, there does not exist any evidence-based strategies to address the problem of hypotension in HFrEF patients who are not optimized on GDMT. Midodrine is an alpha-adrenergic agonist (α1-AR) that exerts its effects on peripheral venous and arteriolar vasculature to increase blood pressure. This medication has been used off-label by some clinicians in the hypotensive HFrEF population to increase blood pressure and has been reported to have beneficial effects in improving GDMT utilization as well as increasing left ventricular ejection fraction (LVEF) in published case reports/case series. There does not exist any randomized prospective data on the use of midodrine in the hypotensive HFrEF population. The investigators' objective is to complete the first open-label, randomized control trial of midodrine in the hypotensive HFrEF population to demonstrate feasibility in performing a trial in this patient population and to show efficacy in increasing blood pressure without associated harm. The results of this trial will be used as the foundation and rationale for future studies assessing the impact of midodrine use on GDMT utilization as well as hard cardiovascular outcomes in the hypotensive HFrEF population, including hospitalizations for heart failure and mortality.

This is a multicenter, randomized, open-label pilot study to evaluate whether stepwise withdrawal of two heart failure medications-angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitor (SGLT2i)-is safe in patients with Heart Failure with improved Ejection Fraction (HFimpEF) whose underlying structural cause (valvular heart disease or ischemic cardiomyopathy) has been completely corrected by surgery or intervention. Eighty adult patients (40 per arm) whose left ventricular ejection fraction (LVEF) has recovered to 50% or higher and whose NT-proBNP is ≤ 250 ng/L will be randomized 1:1 to either (1) stepwise withdrawal of ARNI followed by SGLT2i over one month under close echocardiographic monitoring, or (2) continuation of their current guideline-directed medical therapy. The primary outcome is the change in LVEF at 12 months, with non-inferiority of the withdrawal strategy declared if the LVEF decline is within 5 percentage points of the continuation arm. Secondary outcomes include cardiovascular death, heart failure hospitalization, NT-proBNP, quality of life (KCCQ-12), 6-minute walk distance, and adverse events. Results from this pilot will inform the design and sample size of a subsequent definitive non-inferiority trial and may provide initial evidence to guide deprescribing decisions in clinical practice.

The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study. The hypotheses for this trial are: * HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.

In this single-center, longitudinal observational study, we will comprehensively examine clinical characteristics, proteomic, metabolomic, genomic and imaging data to better understand how different heart failure types may develop and progress over time. We will evaluate distinct sub-groups of heart failure (also known as heart failure phenotypes) and cardiomyopathies including amyloidosis with an ultimate goal of bringing the right medications and therapy to the right patients to optimize benefit and minimized side effects, an effort to improve precision medicine in heart failure.

The purpose of this study is to compare the impact of inspiratory muscle training (IMT) combined with cardiac rehabilitation (CR) on cardiovascular function in patients with heart failure.

Cognitive impairment (CI) is highly prevalent in patients with heart failure with reduced ejection fraction (HFrEF), which has significant implications for disease management, quality of life and clinical outcomes. Currently, there are no specific treatments for CI aside from the current standard of care therapy for HF, making this a high unmet medical need. Impaired cerebral autoregulation is a proposed mechanistic factor that leads to cerebral hypoperfusion, ischemic damage and the development for CI. Preclinical data indicates that restoring CFTR-protein expression normalizes cerebral microvascular function and cerebral blood flow (CBF) in models of HF. The purpose of this study is to investigate whether CFTR-targeting therapy enhances cerebral perfusion and cognitive function in heart failure patients using the CFTR-corrector Lumacaftor.

An increasing number of guideline-directed medical therapies (GDMT) have been developed for patients with chronic heart failure with reduced ejection fraction (HFrEF). When used in combination at recommended doses, patients often experience significant improvements in cardiac function, quality of life, and survival.1,2 However, GDMT underuse occurs for the vast majority of patients with HFrEF. Two recent trials demonstrated improved GDMT prescribing during a clinic visit, each using automated delivery of a patient-centered decision support tool to promote a proactive and holistic approach to prescribing: EPIC-HF (NCT03334188) tested a brief video and checklist document sent to patients just prior to a clinic visit encouraging them to work with their clinicians to make at least 1 positive change to their GDMT; PROMPT-HF (NCT05433220) tested tailored electronic health record (EHR) alerts for GDMT intensification delivered to clinicians during clinic visits. The current I-I-CAPTAIN-HF study aims to broadly implement and test the EPIC-HF patient-facing and PROMPT-HF clinician-facing tools for HFrEF medication intensification at 5 health systems around the country through a pragmatic cluster-randomized implementation-effectiveness trial. This will occur through an initial phase of adaptation of the 2 tools at each health system. Once ready, the 2 tools will be tested using a 2x2 randomization at the clinician-level. In parallel, formal assessment of the implementation of EPIC-HF and PROMPT-HF will work to understand the most effective means of intervention design and delivery, as well as adaptations due to contextual factors to optimize use.

The CardioClip study is exploring the use of a wireless sensor to monitor pressure in the pulmonary artery. This sensor is inserted much like the mTEER procedure, a non-surgical method through a vein in the groin. The investigators want to find out if the sensor, by constantly sending information about heart function, can help improve patient outcomes. This means doctors could adjust medications based on real-time pressure changes detected by the sensor. The results from this study will help pave the way for future trials, asking if using these wireless sensors could benefit people with valve disease and heart failure.

The benefit of weight loss in patients with obesity and heart failure with reduced ejection fraction (HFrEF) is controversial. Semaglutide has shown cardiovascular (CV) risk-reduction and impact on CV risk factors including overweight, dysglycaemia and hypertension in subjects with type 2 diabetes (T2D). The STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) recently demonstrated, at 1-year, to not only reduce weight considerably, but also significantly improve health-related quality of life, functional status scores and 6-min walk distance in patients with heart failure with preserved ejection fraction (HFpEF). Also, the recently concluded SELECT trial was the first CV outcome trial with semaglutide in patients with overweight or obesity and established CV disease, including heart failure (but no T2D). Semaglutide demonstrated a 20% reduction in MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. These landmark findings have important implications for clinicians -as they mean that weight loss and/or semaglutide as anti-obesity pharmacotherapy could be a treatment strategy for secondary prevention of CV disease in patients with overweight or obesity. It is, however, unknown whether weight loss with either calorie-restricted diet or semaglutide has beneficial effects in obese subjects with heart failure and reduced ejection fraction. Also it is unclear whether semaglutide has cardiovascular benefits irrespective of starting weight and amount of weight loss. Purpose: The study aims to investigate whether weight loss treatment with semaglutide is superior to weight loss with calorie-restricted diet in improving peak oxygen uptake in patients with obesity and heart failure with reduced ejection fraction.

This is a prospective, observational study evaluating whether heart sounds (phonocardiograms) and three-lead electrocardiograms (ECGs) recorded using the Eko CORE 500 digital stethoscope can help detect pulmonary hypertension (PH) and low left ventricular ejection fraction (EF ≤ 40%). PH is a condition characterized by high blood pressure in the pulmonary arteries, which can lead to heart failure and carries significant risks if undiagnosed. Low EF, which indicates reduced pumping ability of the heart, is also associated with increased risk of severe cardiac events but can remain undetected because patients often have no symptoms or only nonspecific symptoms. In this study, adults undergoing clinically indicated echocardiograms or right heart catheterization at outpatient sites will be invited to participate. Participants will complete a single study session lasting about 20 minutes, during which heart sounds and a three-lead ECG will be collected using the Eko CORE 500 device. If participants have had a clinical 12-lead ECG within 30 days of their echocardiogram or right heart catheterization, those data may also be used for analysis. A clinically indicated echocardiogram or right heart catheterization (RHC) performed within seven days before or after the Eko CORE 500 recording will serve as the reference standard to confirm the presence or absence of PH and low EF. Up to 3,850 participants may be enrolled across multiple sites to ensure that approximately 3,500 complete the study. The data collected will be used to develop and validate artificial intelligence (AI) algorithms that aim to detect PH and identify low EF, potentially enabling earlier and simpler screening for these conditions in clinical practice.

To evaluate whether percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) combined with guideline-directed medical therapy (GDMT), compared to GDMT alone, reduces the time to first occurrence of major adverse cardiovascular events (MACE) during a median follow-up of at least 24 months, measured at the time the last enrolled patient reaches 12 months, in patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤40%. MACE is a composite of cardiovascular \[CV\] death, myocardial infarction (MI), heart failure (HF) related rehospitalization, heart transplantation, requirement for durable left ventricular assist device \[LVAD\] implantation, or worsening heart failure treated as an out-patient requiring treatment with intravenous medications.

STRATUS-PCI is a pilot clinical trial that compares two ways of running a small heart pump called Impella CP during a high-risk procedure to open blocked heart arteries (percutaneous coronary intervention, or PCI) in patients with weakened heart muscle. The pump is placed temporarily through an artery in the leg and sits across the aortic valve to help maintain blood flow during the procedure. Fifty patients will be randomly assigned in equal numbers to one of two pump settings: an automatic mode that adjusts flow up to higher levels as needed, or a fixed lower-flow mode (P-2). The doctor performing the heart procedure will not know which setting is being used (double-blind). A separate doctor monitors blood pressure and is allowed to change the pump setting at any time if the patient becomes unstable. The main question is whether the automatic mode helps doctors complete the planned heart procedure more successfully and without drops in blood pressure or other complications. Results will help design a larger future trial.

Heart failure (HF) continues to be a leading cause of morbidity and mortality worldwide, despite advances in treatment. HF is often characterized by an altered metabolism in the heart, where glucose is favored over fatty acids as the primary energy substrate. This metabolic shift has been hypothesized to contribute to disease progression. Previous studies using animal models have demonstrated that restoring fatty acid metabolism through dietary intervention can reverse the adverse metabolic effects and improve heart function. A transgenic murine model with mitochondrial defects, for instance, exhibited improved cardiac function after an HFD intervention. These findings were reinforced by a translational pig model of non-ischemic DCM, where a high-fat diet significantly improved LVEF compared to a standard diet. Building upon these promising preclinical results, a small-scale human study showed that lipid infusion, rather than glucose, improved cardiac function in HF patients. However, the long-term benefits of a HFD in heart failure patients have yet to be thoroughly explored. The HF4HF trial aims to fill this gap by evaluating the effects of an HFD over a two-month period in patients with non-ischemic DCM and reduced LVEF. The "High Fat Diet for Heart Failure" (HF4HF) study is a proof-of-concept randomized controlled trial designed to investigate the efficacy of a high-fat diet (HFD) as a therapeutic intervention in patients with non-ischemic dilated cardiomyopathy (DCM) and reduced left ventricular ejection fraction (LVEF). The study hypothesizes that cardiac metabolic reprogramming, achieved through a controlled nutritional intervention involving an HFD, can enhance systolic function, myocardial energetics, and overall heart function in heart failure (HF) patients. Cofunded by the European Commission and national entities, the trial is spearheaded by a consortium of cardiovascular research centers across four countries: Spain, Italy, France, and Romania.

Heart failure with reduced ejection fraction (HFrEF) is frequently associated with abnormalities in body composition, including reduced skeletal muscle mass and sarcopenia, which are independent predictors of reduced exercise tolerance, impaired quality of life, and increased mortality. Despite advances in pharmacological therapy, evidence-based non-pharmacological strategies aimed at preventing muscle mass loss remain limited. This randomized controlled trial aims to evaluate the effects of dietary intervention based on the DASH diet with high-protein elements, resistance exercise training, and their combination on skeletal muscle mass, functional capacity, echocardiographic parameters, biochemical markers, and quality of life in patients with HFrEF.

DigiCare-HFrEF is an investigator-initiated, multicentre, randomised, open-label, endpoint-blinded, superiority trial designed to evaluate whether a structured digital remote-management platform can optimise guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) after hospital discharge. Eligible adults (≥18 years) with a confirmed diagnosis of HFrEF within the past 3 months (left ventricular ejection fraction ≤40%) who are not optimally treated with GDMT-defined as at least two of the four foundational drug classes (ACEi/ARB or ARNi, β-blocker, MRA, SGLT2 inhibitor) either not initiated or prescribed at \<50% of the target dose-will be randomly assigned in a 1:1 ratio to digital remote management or usual care. In the intervention arm, patients will report symptoms and key physiologic measures (e.g., blood pressure, heart rate, and body weight) via the platform; an algorithm will perform risk stratification and generate GDMT optimisation suggestions and decongestion prompts, as well as a comprehensive management for core health metrics, which are reviewed and confirmed by clinicians before implementation. The primary endpoint is the change in GDMT score from baseline to 3 months (ΔGDMT).

The Yale HF Registry is a live EHR based registry that allows for retrospective and real-time monitoring of Heart Failure case across the Yale New Haven Health System.