Cardiac amyloidosis and heart failure phenotypes: a prognostic study of systolic function markers

Background Cardiac amyloidosis (CA), including light chain (AL), hereditary transthyretin (ATTRv), and wild-type transthyretin (ATTRwt), leads to heart failure (HF). Cardiologists use the ESC guidelines to classify patients with HF based on left ventricular ejection fraction (LVEF): reduced (≤40%; HFREF), moderately reduced (41–49%; HFmrEF), and preserved (≥50%; HFPEF), tailoring HF treatment accordingly. CA is commonly associated with HFpEF, with a smaller proportion presenting with HFmrEF and HFrEF. This study aimed to assess the distribution of HF types in CA and their relationship with other left ventricular (LV) systolic function parameters such as global longitudinal strain (GLS) and cardiac index (CI) across amyloidosis subtypes. Methods We retrospectively included symptomatic AL, ATTRv, and ATTRwt CA patients from our French referral center. LVEF was classified per ESC guidelines and compared to GLS and CI. Survival was assessed using Kaplan-Meier analyses and Cox regression. A decision tree incorporating LVEF, GLS, and CI was used to stratify patients into prognostic groups. Results Among 2244 patients, 557 had AL, 392 had ATTRv, 1137 had ATTRwt, and 158 were ATTR being genotyped. Of these, 61.4% presented with HFpEF, 19.0% with HFmrEF, and 19.6% with HFrEF. In AL, 13.6%, 18%, and 68.4% were classified as HFrEF, HFmrEF, and HFpEF, respectively. In ATTRv, 28.3%, 15.3%, and 56.4% were HFrEF, HFmrEF, and HFpEF, respectively. In ATTRwt, 20.2%, 21.2%, and 58.6% were HFrEF, HFmrEF, and HFpEF, respectively. LVEF correlated moderately with GLS (r = 0.673), with stronger correlations in ATTRv (r = 0.776) compared to AL (r = 0.650) and ATTRwt (r = 0.644). LVEF correlated weakly with CI (r = 0.392). Median survival was 7 months [3–31] for AL, 28 months [12–54] for ATTRv, and 23 months [10–38] for ATTRwt. Survival differed by HF type: 30 months [18–41] for HFrEF, 40 months [20–42] for HFmrEF, and 51% survival at 48 months for HFpEF. Among patients with GLS ≤8.2%, median survival was 34 months [25–39], while those with GLS >14% had 71% survival at 48 months. A CI ≤1.96 L/min/m² was associated with a median survival of 29 months [17–37], with better outcomes in higher CI quartiles. A decision tree identified four prognostic groups, with hazard ratios for 4-year mortality ranging from 1.63 (LVEF ≥50%, GLS ≤11%) to 3.68 (LVEF ≤49%, CI ≤1.96 L/min/m²), reaching 12.34 in AL amyloidosis for the most severe group. Conclusions In CA, about 40% of patients present with reduced LVEF. Cardiologists should be aware that CA is not exclusively associated with HFpEF and that patients with reduced LVEF have worse prognosis. LV systolic function, assessed via LVEF, GLS, and CI, is a critical predictor of survival in CA, with distinct patterns across AL, ATTRv, and ATTRwt subtypes. Combining these parameters provides a robust prognostic tool for personalized management and treatment of CA.