Reduced Ejection Fraction At Diagnosis Is An Independent Predictor Of Mortality In Transthyretin Amyloid Cardiomyopathy

Introduction: The prevalence of reduced ejection fraction (HFrEF) in transthyretic cardiac amyloidosis (ATTR-CA) and its prognostic implications have not been well studied. Hypothesis: We hypothesized that reduction in ejection fraction in ATTR-CA is associated with poor prognosis. Methods: We analyzed all patients with the diagnosis of ATTR-CA. ATTR-CA was diagnosed by positive PYP and negative serum studies for AL amyloidosis. The transthoracic echocardiogram (TTE) at the time of PYP was used to identify patients with reduced EF <50% (ATTR-rEF) and preserved EF ≥ 50% (ATTR-pEF). Kaplan-Meier curve for survival between the two groups and adjusted cox proportional hazard models were generated. Results: Of the 124 ATTR-CA patients (mean age of 79.9 ± 7.4, 87% men, 90% Caucasians), 51 (41%) were ATTR-rEF. Compared to ATTR-pEF, at the time of PYP, ATTR-rEF were more symptomatic ( NYHA-FC ≥ 3, 61% vs 26%, p<0.001), had lower prevalence of obstructive coronary artery disease (CAD)(37% vs 55%, p=0.05), worse mean diastolic dysfunction (3 vs 2.15, p<0.01), lower tricuspid annular plane systolic excursion (TAPSE <1.7, 59% vs 25%, p<0.001) and reduced renal function ( creatinine, 1.63 ± 0.85 vs 1.27 ± 0.55 mg/dl, p<0.01). There was no difference in terms of biomarkers (BNP, p=0.1 and troponin, p=0.3) and interventricular septal thickness (p=0.2). Over a mean follow up period of 1.5 years, 27 (22%) patients died. ATTR-rEF was associated with higher mortality compared to ATTR-pEF (35% vs 12%, p=0.002; HR 3.7, 95%CI 1.62-8.63, p<0.01, fig. 1A). After adjustment for multiple cofounders including TAPSE and serum creatinine, reduced EF was an independent predictor of mortality (HR 3.02, 95% CI 1.30-7.10, p=0.01). When divided into EF≥ 50%, EF 41-49% and EF ≤ 40%, there was stepwise increase in the risk of mortality (p<0.01, fig. 1B). Conclusion: HFrEF is present in more than one-third of patients with ATTR-CA at the time of diagnosis, and is an independent predictor of mortality in ATTR-CA.