HFSA 2025 Preview: 8 Late-Breaking Studies to Know

The Heart Failure Society of America (HFSA) Annual Scientific Meeting returns September 27–30, 2025, in Minneapolis, Minnesota, bringing together leading investigators, clinicians, and industry to spotlight the latest advances in heart failure research and patient care.
This year’s late-breaking clinical science program underscores both the diversity and urgency of innovation across the field—from disease-modifying therapies in hypertrophic cardiomyopathy and amyloidosis, to novel agents for acute decompensation and cardiogenic shock, to precision-focused analyses that refine treatment strategies in HFpEF and HFrEF.

To help prepare for the meeting, our editorial team has compiled a list of 8 late-breaking clinical trials to know from the meeting, which are highlighted below.

1. Safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy: a 96-week analysis from FOREST-HCM

Presentation Time: Sunday, September 28, 9:41 - 9:48 CST
Presenter: Ahmad Masri, MD
Background Info: FOREST-HCM, a landmark phase 2/3 trial investigating aficamten in patients with obstructive hypertrophic cardiomyopathy, is an ongoing open-label extension study expected to conclude in March of 2028. 48-week results from the trial were published in June of 2025, indicating aficamten’s efficacy and durability in treating obstruction and symptom burden, as well as lowering cardiac biomarker levels. This presentation will provide data on the next follow-up interval for the patient group, examining the long-term maintenance of positive endpoints and further establishing the safety and efficacy of aficamten.1

2. Divergent Effect of Aficamten Versus Metoprolol on Exercise Performance in Obstructive Hypertrophic Cardiomyopathy: A Prespecified Analysis of MAPLE-HCM

Presentation Time: Sunday, September 28, 9:49 – 9:56 CST
Presenter: Roberto Barriales-Villa, MD, PhD
Background Info: MAPLE-HCM was a double-blind, double-dummy trial comparing aficamten to metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy. Investigators found aficamten superior to metoprolol in improving peak oxygen uptake and hemodynamics, as well as decreasing symptoms. Results were initially published in August of 2025.This presentation from Cytokinetics will more specifically analyze both medications’ outcomes on exercise performance, highlighting another clinically relevant area of comparison to further establish aficamten’s superiority.2

3. Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis from ATTRibute-CM

Presentation Time: Sunday, September 28, 10:05 – 10:12 CST
Presenter: Kevin Alexander, MD
Background Info: The ATTRibute-CM phase 3 study evaluated the safety and efficacy of acoramidis (Attruby) HCI 800 mg in patients with symptomatic transthyretin amyloid cardiomyopathy. Completed in May of 2023, the study highlighted a substantially better 4-step primary hierarchical outcome, components of which included mortality, morbidity, and function.This upcoming exploratory analysis will provide an alternative analysis of the existing data, highlighting cumulative and recurrent cardiovascular outcomes.3

4. Vericiguat efficacy and safety across baseline background therapy in contemporary ambulatory patients with HFrEF enrolled in the VICTOR trial

Presentation Time: Monday, September 29, 9:29 – 9:36 CST
Presenter: Javed Butler, MD, MPH
Background Info: VICTOR, a double-blind, placebo-controlled, phase 3 trial investigating vericiguat (VERQUVO) in patients with heart failure with reduced ejection fraction, ultimately saw no significant reduction in a composite endpoint of time to cardiovascular death or heart failure hospitalization. However, the data did show fewer cardiovascular deaths in the vericiguat group than placebo.This trial will examine the safety and efficacy of vericiguat specifically across baseline background therapy.4

5. Safety and Efficacy of Intravenous administration of Istaroxime for 48 hours in Patients with SCAI C Cardiogenic Shock due to acute heart failure

Presentation Time: Monday, September 29, 9:52 – 9:59 CST
Presenter: Marianela Barros, MD
Background Info: Istaroxime proved its efficacy in patients hospitalized for acute heart failure related Society for Cardiovascular Angiography and Interventions (SCAI) stage B pre-cardiogenic shock in a 2022 trial. The investigative therapy improved blood pressure and some echocardiography measures related to heart failure and maintained a good tolerability.This upcoming presentation will instead examine SCAI stage C cardiogenic shock, detailing istaroxime’s efficacy in an as-yet-uninvestigated patient group with acute heart failure.5

6. Effects of Tirzepatide in Obesity-Related HFpEF by Sex: A Prespecified Secondary Analysis from the SUMMIT Trial

Presentation Time: Monday, September 29, 10:00 – 10:07 CST
Presenter: Barry Borlaug, MD
Background Info: Initially presented at the American Heart Association 2024 Scientific Sessions, the SUMMIT trial demonstrated the safety and efficacy of tirzepatide in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Shortly after the presentation, parent company Eli Lilly and Company withdrew their application for approval in heart failure care.This secondary analysis will specifically examine the effects of tirzepatide based on sex among the same patient group.6

7. GDF-15 Neutralization in Patients with Heart Failure: Primary Results of the GARDEN-TIMI 74 Trial

Presentation Time: Monday, September 29, 10:08 – 10:15 CST
Presenter: David Berg, MD, MPH
Background Info: Pfizer’s GARDEN-TIMI 74 phase 2 trial is testing the effects of ponsegromab, a monoclonal antibody directed against growth differentiation factor (GDF)-15 on health status and physical activity in patients with heart failure and elevated circulating GDF-15 concentrations. Patients were randomly assigned to receive either ponsegromab or placebo every 4 weeks for the 20-week treatment period. Follow-up was conducted at weeks 24 and 32.The presentation will provide a first look at the primary results from the study, which was completed in March and investigated a total of 455 participants with heart failure.7

8. Danicamtiv restores ventricular and atrial function in patients with dilated cardiomyopathy caused by genetic variants that depress sarcomere function

Presentation Time: Monday, September 29, 10:20 – 10:27 CST
Presenter: Neal Lakdawala, MD
Background Info: Danicamtiv, a second-generation cardiac-specific myosin activator in development by Kardigan, entered clinical trials in 2022. Since then, it has displayed improved function compared to first-generation myosin activator omecamtiv mecarbil in patients with heart failure. This presentation will highlight the effects of danicamtiv in patients with genetically induced dilated cardiomyopathy.8

References

1. Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of Aficamten in Adults with HCM (FOREST-HCM). ClinicalTrials.gov identifier: NCT04848506. Updated June 4, 2025. Accessed September 23, 2025. https://clinicaltrials.gov/study/NCT04848506

2. Garcia-Pavia P, Maron MS, Masri A, et al. Aficamten or metoprolol monotherapy for obstructive hypertrophic cardiomyopathy. New England Journal of Medicine. 2025;393(10):949-960. doi:10.1056/nejmoa2504654

3. Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and safety of ACORAMIDIS in transthyretin amyloid cardiomyopathy. New England Journal of Medicine. 2024;390(2):132-142. doi:10.1056/nejmoa2305434

4. Butler J, McMullan CJ, Anstrom KJ, et al. Vericiguat in patients with chronic heart failure and reduced ejection fraction (Victor): A double-blind, placebo-controlled, randomised, phase 3 trial. The Lancet. Published online August 29, 2025. doi:10.1016/s0140-6736(25)01665-4

5. Metra M, Chioncel O, Cotter G, et al. Safety and efficacy of istaroxime in patients with acute heart failure-related pre-cardiogenic shock - a multicentre, randomized, double-blind, placebo-controlled, parallel group study (SEISMiC). Eur J Heart Fail. 2022;24(10):1967-1977. doi:10.1002/ejhf.2629

6. A Study of Tirzepatide (LY3298176) in Participants with Heart Failure with Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial. ClinicalTrials.gov identifier: NCT04847557. Updated August 20, 2025. Accessed September 23, 2025. https://clinicaltrials.gov/study/NCT04847557

7. A Study of Ponsegromab in People with Heart Failure (GARDEN TIMI 74). ClinicalTrials.gov identifier: NCT05492500. Updated June 13, 2025. Accessed September 23, 2025. https://clinicaltrials.gov/study/NCT05492500

8. Choi J, Wood PT, Holmes JB, et al. Differential effects of myosin activators on myocardial contractile function in nonfailing and failing human hearts. Am J Physiol Heart Circ Physiol. 2025;328(1):H161-H173. doi:10.1152/ajpheart.00252.2024