Sex-specific differences in cardiac transthyretin amyloidosis: addressing the diagnostic gap in women

TL;DR

This study finds that women with a type of heart disease called ATTR-CM are diagnosed later and show different symptoms than men, suggesting a need for sex-specific diagnostic criteria.

Contribution

The study identifies sex-specific clinical and echocardiographic differences in ATTR-CM patients, highlighting the need for sex-adapted diagnostic criteria.

Findings

Women with ATTR-CM had lower interventricular septal diameter, left ventricular mass, and stroke volume compared to men.

Diagnostic delay was significantly longer in women, with a median of 750 days versus 86 days in men.

Sex-specific echocardiographic differences persisted despite treatment, with women showing lower functional capacity.

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure. With a male:female ratio of approximately 10:1, current evidence including diagnostic criteria is largely based on male-dominant collectives. Sex-specific differences may contribute to delayed diagnosis in women. This study investigates these differences in a real-world setting.

In this retrospective single-centre cohort study, all patients at West German Amyloidosis Center diagnosed with ATTR-CM between 2018 and 2024 were analysed. Clinical, echocardiographic, and laboratory parameters as well as outcomes under transthyretin stabilizer therapy at 6 and 12 months were evaluated. Among 240 patients, 34 (14.2%) were women. Compared to men, women had lower interventricular septal diameter, left ventricular mass, and stroke volume, but higher ejection fraction. Troponin I levels were lower and renal function was worse in women. Diagnostic delay was significantly longer in women (median 750 vs. 86 days, P = 0.022). Despite therapy, sex-specific echocardiographic differences persisted, and functional capacity remained lower in women, although NYHA functional class was comparable.

Transthyretin amyloid cardiomyopathy presents with persistent sex-specific differences that may contribute to diagnostic delay in women. Current diagnostic thresholds may not adequately reflect female disease patterns, underscoring the need for sex-adapted diagnostic criteria to improve early detection and management.

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