Heart Failure Society of America 2026 Preview: 6 Trials to Watch

The Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 is scheduled to begin on October 9, 2026, and is expected to present the clearest view of how heart failure (HF) care has evolved in the past year. Readouts from major trials of both investigational drugs and operations to improve major biomarkers and reduce side effects have been announced, with many more likely to be revealed once the conference begins.

The HCPLive editorial team will be on-site in Phoenix, Arizona for the duration of the conference, providing both written coverage and key clinician perspectives on all of the most impactful news. Keep an eye on our coverage here – and in the meantime, check out what to expect from HFSA 2026 below:

Trials to Watch

1. A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic HFrEF: The Cycle-1 REF Trial

Presentation Time: 9:27 am MT on Sunday, October 11

Presenter: James Udelson, MD

The first half of the CYCLE trials presented at HFSA focuses on HF with reduced ejection fraction (HFrEF), contrasting 3 doses of tovinontrine (CRD-750) with placebo. Roughly 560 patients were enrolled with a primary endpoint of change in NT-proBNP, which is released by the heart during HF. This trial and its companion finished enrollment in 2025, and detailed results will be presented in full at the conference for the first time.

2. A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic HFpEF: The Cycle-2 PEF Trial

Presentation Time: 9:34 am MT on Sunday, October 11

Presenter: James Udelson, MD

Cycle-2 PEF is the second trial in the Cycle pairing, studying patients with HF with preserved ejection fraction (HFpEF). Roughly 300 patients were enrolled, and the trial evaluated a single dose of tovinontrine against placebo for the same endpoint as Cycle-1 REF. The orally administered PDE9 inhibitor aims to enhance the natriuretic peptide signaling (NPS) pathway; parent company Cardurion is the first company to bring this type of inhibitor into clinical development for chronic HF.

3. Effect of Eplontersen on Health Status in Patients with Transthyretin Amyloid Cardiomyopathy Enrolled in the CARDIO-TTRansform Trial

Presentation Time: 9:48 am MT on Sunday, October 11

Presenter: Brett Sperry, MD

While eplontersen failed to achieve its primary endpoint of reducing cardiovascular death and recurrent cardiovascular events compared to placebo in the CARDIO-TTRansform trial, patients receiving the drug did display a lesser decline in exercise capacity and health-related quality of life. Clinicians have also indicated potential nominal improvements in these metrics. To address this potential benefit, this analysis will be presented at HFSA 2026 as investigators continue to analyze the findings from the original trial.

4. Global Efficacy Of Aficamten In Nonobstructive Hypertrophic Cardiomyopathy: Results From ACACIA-HCM

Presentation Time: 9:26 am MT on Monday, October 12

Presenter: Martin Maron, MD

Results from the ACACIA-HCM trial were first presented at the European Society of Cardiology Congress in Munich, Germany – based on those data, investigators have concluded that aficamten effectively improved exercise capacity and patient-reported health status versus placebo in patients with symptomatic nonobstructive HCM. After 36 weeks, the patients assigned to aficamten saw significant changes in peak oxygen uptake and reductions in left ventricular ejection fraction with limited adverse events.

5. Prevalence of Cardiovascular Inflammation and Associated Patient Characteristics and Biomarker Profiles Across the Heart Failure Spectrum in the United States: Results From the POSEIDON Study

Presentation Time: 9:50 am MT on Monday, October 12

Presenter: Marat Fudim, MD

First published in May 2026, the POSEIDON study was constructed to evaluate the prevalence of inflammatory risk in patients with HF across the EF spectrum. Specifically, it examined high sensitivity C-reactive protein (hsCRP) in this patient population, and ultimately determined that elevated hsCRP levels were present in roughly 4 in 10 patients. Additionally, it has been associated with more severe HF and a cardio-kidney-metabolic phenotype. At HFSA 2026, further details from the study will be presented, continuing to establish the association between HF and inflammation.

6. Six-Month Outcomes of Subcutaneous Cardiac Microcurrent Therapy: Comparative Analysis of the C-MIC III Pilot Study with the C-MIC II Randomized Trial

Presentation Time: 10:14 am MT on Monday, October 12

Presenter: Stefan Simovic, MD, PhD

C-MIC II was an open-label, randomized controlled trial aiming to evaluate the original surgical Cardiac Microcurrent (CMIC) device on top of guideline-directed medical therapy to improve left ventricular ejection fraction (LVEF). The trial ultimately found that, after 6 months, the patients receiving the implanted device saw a significant mean improvement in LVEF, 6-minute walk distance, and functional NYHA class. The C-MIC III study, meanwhile, is a first-in-human trial of a less invasive, subcutaneous approach to delivering the same microcurrent therapy. These data will be presented for the first time at HFSA 2026, contrasting invasive surgery against a simpler, less involved operation to accomplish the same goal.