Prevalence, incidence, risk factors and prognostic role of atrial fibrillation in amyloidotic cardiomyopathy of different etiologies

Purpose: Although atrial fibrillation (AF) is a well known complication of amyloidotic cardiomyopathy (AC), a precise clinical, pathophysiological and prognostic characterization is not available. The aim of our study was to evaluate prevalence, incidence, risk factors for AF and prognostic significance of AF in the three main etiological subgroups of AC: light-chain (AL), hereditary transthyretin-related (ATTR) and non-mutant transthyretin-related (wtTTR). Methods: We studied 255 patients with AC (121 AL, 92 ATTR, 42 wtTTR) and assessed clinical, ECG, echocardiographic and hemodynamic details at presentation. Results: Prevalence of AF at first evaluation was 15% overall: 9% in AL, 11% in ATTR and 40% in wtTTR. During a median follow up of 1.2 (IQR 0.4–2.9) years, seven other patients developed AF (1.5% person-years). At univariate analysis, age (OR 1.1, 95% CI 1.05–1.13), NYHA class III-IV (OR 4.12, 95% CI 1.99–8.55), wtTTR etiology (OR 6.8, 95% CI 2.84–16.30), left ventricular ejection fraction (LVEF) (OR 0.95, 95% CI 0.93–0.98), right atrial pressure (OR 1.13, 95% CI 1.04–1.23) and pulmonary capillary wedge pressure (OR 1.07, 95% CI 1.01–1.14) were significantly (p<0.01) associated with the risk of AF. At multivariate analysis however, only age (OR 1.08, 95% CI 1.04–1.14), LVEF (OR 0.96, 95% CI 0.93–0.99) and right atrial pressure (OR 1.14, 95% CI 1.03–1.26) remained associated as independent variables. Left ventricular wall thickness was not associated with AF in any of the three etiological subgroups. Warfarin was prescribed to all AF patients and none suffered thromboembolic events. AF was not associated with an increased mortality even though survival free from heart failure was significantly lower in patients with AF in the ATTR (event rate 14.6% vs 1.1% person-years, p=0.0001) and wtTTR groups (event rate 15.2% vs 5.4% person-years, p=0.05). Conclusions: Prevalence of AF at presentation was 15% in the entire cohort, with a maximum rate of 40% in wtTTR patients. Left ventricular systolic and diastolic dysfunction, but not wall thickness, were associated with AF. AF was an incremental risk factor for mortality or heart failure in patients with TTR-related amyloidosis.