Prognostic value of CT-derived pectoralis muscle area in tafamidis-treated ATTRwt cardiomyopathy

Background Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is a progressive disease caused by myocardial deposition of misfolded transthyretin1). Tafamidis improves clinical outcomes, but prognosis remains heterogeneous and optimal risk stratification is not fully established. Sarcopenia is an important determinant of outcomes in cardiovascular disease2) and cardiac amyloidosis. Chest computed tomography (CT), routinely performed in ATTR-CM evaluation, allows objective quantification of skeletal muscle mass. However, the prognostic value of CT-derived muscle measurements in tafamidis-treated ATTRwt-CM remains unclear. Objective To evaluate whether sarcopenia assessed by pectoralis muscle area (PMA) on routine chest CT predicts clinical outcomes in tafamidis-treated ATTRwt-CM. Methods We retrospectively studied 74 consecutive patients with ATTRwt-CM who underwent chest CT before tafamidis initiation. PMA was measured at the fourth thoracic vertebral level as the sum of bilateral pectoralis major and minor muscle areas. Patients were stratified into sex-specific small and large PMA groups according to median values. The primary endpoint was a composite of all-cause death, heart failure hospitalization, or cardiovascular events. Cox proportional hazards models were used to identify predictors of outcomes. To evaluate the prognostic value of PMA across disease severity, patients were further stratified using the Kumamoto disease progression score (0–3), a three-domain model of ATTR-CM severity3). Low scores (0–1) represent relatively early-stage disease with better prognosis, whereas high scores (2–3) indicate advanced disease with poorer outcomes. Kaplan–Meier analyses were performed within these categories. Results The mean age was 79 ± 5.9 years and 90% were male. Patients were divided into small PMA (n=37) and large PMA (n=37) groups. During a mean follow-up of 32 ± 19 months, the small PMA group showed significantly higher rates of the primary endpoint (log-rank p < 0.01). (Figure 1) Small PMA was associated with a markedly increased risk of the primary endpoint (hazard ratio [HR] 3.82, 95% confidence interval [CI] 1.56-9.36, p < 0.001) after adjustment for age, eGFR, and NT-proBNP. Among patients with a low Kumamoto disease progression score (0–1), the small PMA group had a significantly higher incidence of the primary outcome than the large PMA group (log-rank p = 0.0148), whereas no significant difference was observed among patients with high scores (2–3) (log-rank p = 0.256). (Figure 2) Conclusions CT-derived pectoralis muscle area is a powerful independent predictor of adverse outcomes in tafamidis-treated ATTRwt-CM and provides incremental prognostic information beyond established clinical markers. Skeletal muscle assessment using routine chest CT may enable earlier identification of high-risk patients and may improve risk stratification and clinical management in the tafamidis era.Figure 1Figure 2