Research highlighting acoramidis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and danicamtiv for dilated cardiomyopathy (DCM) were presented during the Heart Failure Society of America (HFSA) 2025 meeting, held Sept. 26-29 in Minneapolis, MN, and simultaneously published in JACC. Another study presented at the meeting and published in JACC: Heart Failure looked at the decline in acceptance of advanced heart failure/transplant cardiology (AHFTC) fellowship openings.

ATTRibute-CM: Acoramidis For ATTR-CM

In the first study, acoramidis was associated with a significant 49% reduction in the cumulative risk of cardiovascular mortality or recurrent cardiovascular hospitalizations at 30 months, compared with placebo, in patients with ATTR-CM, according to a post hoc exploratory analysis of data from the ATTRibute-CM trial and its open label extension. The results were presented during HFSA 2025 and simultaneously published in JACC.

A total of 611 patients in the ATTRibute-CM trial were included in this recurrent event analysis. They had been randomized to acoramidis HCI 800 mg acoramidis (n=409) or placebo (n=202) twice daily. On average, they were 77 years old and 88% were White and 9% women. Their mean duration of ATTR-CM was 1.2 years and 90% had wild-type ATTR-CM.

Results showed at 30 months that acoramidis significantly reduced the cumulative risk of cardiovascular mortality or recurrent cardiovascular hospitalizations (hazard ratio [HR], 0.51; p<0.0001). Notably, the treatment effect was seen at one month and the difference between groups increased over time, with 53 events avoided per 100 participants in the treatment arm at 30 months; 19% of the cardiovascular mortality events and 22% of the cardiovascular hospitalization events occurred in the first six months.

Moreover, with acoramidis vs. placebo, cardiovascular mortality was reduced at 42 months (HR, 0.55).

Ahmad Masri, MD, MS, FACC, et al., write that "acoramidis-mediated near-complete TTR stabilization results in early and sustained increases in serum TTR." Furthermore, these findings "underscore the importance of strategies for prompt treatment initiation following a diagnosis of ATTR-CM."

Danicamtiv For DCM

In the second study, danicamtiv, a novel investigational small molecule that selectively-enhances cardiac myosin function, when given in vitro in a phase 2, open label trial was associated with increased activity of wildtype and DCM myosin, thereby increasing force production in cardiac fibers. The results were presented at HFSA 2025 and simultaneously published in JACC.

Furthermore, in this proof-of-principle trial that included 41 participants with DCM, two-weeks of twice-daily oral danicamtiv was well tolerated. Their mean age was 50 years, 37% were women and the baseline LVEF was 33%.

Results showed that treatment-emergent adverse events occurred in 22 participants (54%), with the most common being headache, diarrhea, dizziness and fatigue, and one discontinuation related to COVID-19.

At the end of the treatment period, participants with DCM linked to cardiac beta-myosin heavy chain (MYH7) (n=12) or titin (TTN) (n=14) pathogenic variants showed greater improvement in LVEF from baseline (MYH7, 9%; TTN, 6%) compared to other causes (n=15; 4%).

"We speculate that patients with DCM caused by pathogenic variants in MYH7 or TTN, which impair sarcomere thick filament function, may derive the greatest benefit from treatment with a myosin activator such as danicamtiv," write study investigators Neal K. Lakdawala, MD, and colleagues. "Genetic diagnosis could be used to personalize DCM therapy by identifying patients more likely to benefit from danicamtiv."

Current Trends in AHFTC Fellowship Programs

Finally, a retrospective cohort study to understand the reasons for the decline in accepting fellowships in AHFTC training programs found more than 60% of spots have not been filled over the last five years, and that hospital reputation and clinical volume best predict successful matching, according to research presented at HFSA 2025 and simultaneously published in JACC: Heart Failure.

Eiran Z. Gorodeski, MD, MPH, FACC, et al., examined nine variables for all AHFTC fellowship programs in the U.S. for the 2021-2025 appointment years. They found that 50% of fellows in the AHFTC National Resident Matching Program (NRMP) match trained at only 13 institutions, with 26% of programs failing to match any fellows.

The strongest predictors of match success were offering three or more fellowship positions, performing >50 heart transplantations annually and having the highest U.S. News and World Report rankings, over regional disease burden or program location.

"In the current era of waning interest in AHFTC training, fellowship programs failing to meet these criteria are unlikely to match and face an uncertain future," write Gorodeski and colleagues. "A better understanding of the factors associated with filling AHFTC fellowship positions may allow for more effective strategies to halt the decline of interest in the field."

Investigators also noted geographic disparities, with 17 states not offering any AHFTC fellowships and an additional six states failing to fill any positions.