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).<\/p>\n
The first JACC: Advances study<\/a> 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.<\/p>\n 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).<\/p>\n 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).<\/p>\n “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.”<\/p>\n The second JACC: Advances study<\/a> identified an association between longer delays in ATTR-CM diagnosis with increased likelihood of HF hospitalization and mortality.<\/p>\n 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.<\/p>\n 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).<\/p>\n “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.<\/p>\n The JAMA Cardiology article<\/a>, 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.<\/p>\n 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.<\/p>\n 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.<\/p>\n 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.”<\/p>\n Ciocca, N, Fuentes Artiles, R, Studer Bruengger, A. et al. Sex Differences in Presentation and Outcomes of Transthyretin Amyloid Cardiomyopathy. JACC Adv. 2026 Aug, 5 (8). https:\/\/doi.org\/10.1016\/j.jacadv.2026.103068<\/a>
\nSpencer-Bonilla, G, Fan, J, Varshney, A. et al. Delayed Diagnosis of Transthyretin Cardiac Amyloidosis Is Associated With Heart Failure Hospitalizations and Mortality. JACC Adv. 2026 Aug, 5 (8). https:\/\/doi.org\/10.1016\/j.jacadv.2026.103019<\/a>
\nSherrod CF, Fontana M, Gillmore JD, et al. Effect of Acoramidis on Heart Failure\u2013Related Health Status: A Secondary Analysis of the ATTRibute-CM Randomized Clinical Trial. JAMA Cardiol. Published online July 29, 2026. doi:10.1001\/jamacardio.2026.2413<\/a><\/p>\n
\n Keywords:
\n Patient Reported Outcome Measures, Health Status, Delayed Diagnosis, Heart Failure, Cardiomyopathies
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