Find Recruiting Clinical Trials for Heart Failure

Heart failure has a rich and increasingly differentiated trial landscape by subtype. HFrEF trials (LVEF ≤40%) test novel cardiac myosin activators, next-generation ARNI formulations, oral soluble guanylate cyclase (sGC) stimulators like vericiguat, gene therapy vectors targeting calcium handling proteins (SERCA2a), novel MRA agents, and device optimization strategies. HFpEF trials (LVEF ≥50%) are the most actively enrolling and include SGLT2 inhibitor extension studies, GLP-1 receptor agonist trials (particularly relevant for obese HFpEF patients), novel anti-inflammatory and anti-fibrotic agents, aldosterone synthase inhibitors, and trials combining pharmacotherapy with structured exercise. Cardiometabolic trials test interventions at the intersection of heart failure, obesity, and type 2 diabetes. Device trials test MitraClip for functional mitral regurgitation, CRT optimization, LVAD as destination therapy, and implantable hemodynamic monitoring sensors. Cardiac rehabilitation trials test structured exercise programs and remote monitoring. Knowing your most recent echocardiogram LVEF measurement is essential for trial searching.

HFrEF (heart failure with reduced ejection fraction) and HFpEF (heart failure with preserved ejection fraction) are fundamentally different diseases that happen to share the name "heart failure." HFrEF — defined as LVEF ≤40% — is characterized by a dilated, weakened heart that cannot contract adequately. It has four pillars of guideline-directed medical therapy (ACEi/ARNI, beta-blocker, MRA, SGLT2 inhibitor) that are proven to reduce mortality. Most landmark heart failure trials over the past three decades enrolled HFrEF patients, and the evidence base is robust. HFpEF — defined as LVEF ≥50% — involves a stiff, non-compliant heart that contracts normally but cannot relax and fill properly. It is now the predominant form of heart failure (>50% of cases) and is strongly associated with obesity, hypertension, diabetes, and atrial fibrillation. Historically, HFpEF had no proven disease-modifying therapies — until SGLT2 inhibitors (dapagliflozin and empagliflozin) demonstrated clinical benefit. HFpEF is now the most active frontier in heart failure drug development. From a trial perspective: if your LVEF is ≤40% you are HFrEF; if ≥50% you are HFpEF; 41–49% is HFmrEF. These categories are not interchangeable — the same trial will almost never enroll both HFrEF and HFpEF patients.

Yes — LVEF is the single most critical eligibility criterion in heart failure clinical trials. Almost every heart failure drug trial specifies an exact LVEF threshold or range measured by echocardiogram (or cardiac MRI). Common thresholds: LVEF ≤35% (many HFrEF device and drug trials targeting the most impaired hearts), LVEF ≤40% (standard HFrEF trials), LVEF ≥40% or ≥45% (some HFmrEF-inclusive trials), LVEF ≥45% or ≥50% (HFpEF trials). To determine trial eligibility, you need a recent echocardiogram — ideally within 3–6 months of screening (some trials specify within 12 months). The LVEF must be documented in your medical records. Bring your most recent echocardiogram report to any trial screening appointment. Note that LVEF can change over time — particularly in patients who start or optimize GDMT, where "recovered" EF (LVEF improving to >50% on treatment) may reclassify you from HFrEF to HFpEF. Some trials specifically enroll patients with recovered EF.

The New York Heart Association (NYHA) functional classification is a standardized system for rating the severity of heart failure symptoms based on how much physical activity triggers symptoms. Class I: no limitation of physical activity; ordinary activity does not cause symptoms. Class II: slight limitation; comfortable at rest but ordinary physical activity causes fatigue, palpitations, or dyspnea. Class III: marked limitation; comfortable at rest but less-than-ordinary activity causes symptoms. Class IV: unable to carry out any physical activity without discomfort; symptoms may be present at rest. NYHA class is assessed by your physician based on your reported symptoms and functional status. For clinical trial eligibility: most drug trials enroll NYHA Class II and III patients — symptomatic enough to have meaningful endpoints but stable enough to participate safely over months to years. Class I patients (asymptomatic) may be excluded because disease modification is harder to measure. Class IV patients (severely symptomatic) are often excluded from drug trials due to safety and tolerability concerns, but are specifically targeted by device trials (LVAD, transcatheter procedures) and palliative care studies. Stable NYHA Class III patients in particular have many options.