Three recent studies, two published in JACC: Advances and a third published in JAMA Cardiology, investigate sex differences, delayed diagnosis and the effect of acoramidis on heart failure (HF)-related health status in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

The first JACC: Advances study found a higher risk of major adverse cardiac events (MACE) after diagnosis in women vs. men, but sex was not an independent predictor of outcomes.

Nicola Ciocca, MD, et al., included 567 patients (age 77 years, 9% women) with ATTR-CM, exploring a primary endpoint of first MACE. Overall, women were more likely to be older at diagnosis, have a higher NYHA functional class, higher NT-proBNP and shorter six-minute walking distance. Tafamidis was prescribed in 50% of women and 70% of men (p=0.004).

Although women exhibited a higher rate of MACE (hazard ratio [HR], 1.86; 95% CI, 1.13-3.04; p=0.014), driven by increased HF hospitalizations within the first two years and higher all-cause mortality, there was no independent association between sex and MACE (p=0.23).

"This early disadvantage in women appears to be mainly attributable to older age and more advanced disease stages at diagnosis rather than intrinsic sex-specific differences," write the authors. "Our findings underscore the importance of early diagnosis, comprehensive comorbidity management, and the investigation of sex-specific diagnostic thresholds and imaging red flags."

The second JACC: Advances study identified an association between longer delays in ATTR-CM diagnosis with increased likelihood of HF hospitalization and mortality.

Using Medicare fee-for-service and Veterans Health Administration data, Gabriela Spencer-Bonilla, MD, MS, et al., included 7,770 Medicare beneficiaries and 2,557 veterans with HF and ATTR-CM (median age at diagnosis 81 years) in their analysis. They assessed time-to-diagnosis (days between first HF diagnosis and first amyloid diagnosis) and its association with death or HF hospitalization.

Median time-to-diagnosis was 494 days for the Medicare cohort and 490 days for the veteran cohort. Adjusted results showed that each one-year delay in diagnosis saw a 7% increased risk of death or HF hospitalization (Medicare HR, 1.07; 95% CI, 1.06-1.08; veteran HR, 1.07; 95% CI, 1.05-1.09).

"These findings support diagnostic delay as a clinically meaningful marker of disease progression, with longer delays reflecting more advanced disease at presentation and translating into worse outcomes," state the authors.

The JAMA Cardiology article, a secondary analysis of the ATTRibute-CM trial, found that acoramidis significantly attenuated decline in HF-related health status vs. placebo in patients with ATTR-CM.

A total of 611 participants with ATTR-CM (mean age 77 years, 9% women) were included, with 409 randomized to 800 mg of acoramidis twice daily and 202 to placebo for 30 months. A secondary outcome of the trial was the least-squares mean (LSM) difference in KCCQ-Overall Score (KCCQ-OS) at 30 months.

At month 30, Charles F. Sherrod IV, MD, MSc, et al., observed a "statistically significant, clinically meaningful treatment benefit" for acoramidis vs. placebo (LSM difference, 9.9; 95% CI, 6.0-13.9; p<0.001). Additionally, 47% of acoramidis recipients vs. 30% of placebo recipients had a <5-point decrease in KCCQ-OS from baseline, 46% of acoramidis recipients vs. 31% of placebo recipients had a score >60 and <10-point decrease in from baseline, and 25% of acoramidis recipients vs. 14% of placebo recipients had a >5-point increase from baseline.

According to the authors, "participants receiving acoramidis were more likely to experience stabilization of their health status...these patient-reported benefits complement previously established reductions in mortality and [cardiovascular-related hospitalizations] with acoramidis, indicating that treatment not only improves survival and reduces clinical events, but also attenuates the decline in patients' health status."