Natural History and Disease Progression of Early Cardiac Amyloidosis Evaluated by Echocardiography

Abstract Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Pre-amyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain (AL) or amyloid transthyretin (ATTR)). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 (IQR 1.0, 1.5)cm) ≥ 3 years before the diagnosis of CA and relative wall thickness (RWT) was increased (0.47 (IQR 0.41, 0.50)) ≥ 7 years pre-diagnosis. Between 1 to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction (LVEF)≤ 50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased RWT (0.74 (IQR 0.62, 0.92) vs. 0.62 (IQR 0.54, 0.76), p=0.004) and LV mass index (144 (IQR 129, 191) vs. 115 (IQR 105, 146)g/m2,p=0.020) and reduced LVEF (50 (IQR 44, 58) vs. (60 (IQR 53, 60)%, p=0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography.