Elevated filling pressures but rare restrictive physiology in transthyretin amyloid cardiomyopathy: genotype-specific patterns and the role of left atrial strain

Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with cardiac stiffness and diastolic dysfunction. While recommendations highlight restrictive filling as a common echocardiographic marker in ATTR-CM, a detailed characterization of diastolic dysfunction (LVDD) severity and differences in prevalence between ATTR-CM genotypes have not been explored. In a well-characterized ATTR-CM cohort, we investigated the prevalence, severity and genotype-specific distribution of LVDD and assessed the added value of left atrial reservoir strain (LASr) for its detection. Diastolic dysfunction was graded by transthoracic echocardiography in 100 patients with ATTR-CM (76 hereditary [ATTRv] and 24 wild-type (ATTRwt) according to current ASE/EACVI recommendations, with LASr incorporated for comparison. Restrictive filling was observed in only 22% of the cohort and was more common in in ATTRwt compared with ATTRv (59% vs. 14% respectively). Incorporating LASr into LVDD assessment did not change the proportion of patients with restrictive filling pressure but increased the proportion of patients identified with elevated filling pressure from 53% to 68% and reduced indeterminate cases from 13% to 3%. Restrictive filling in uncommon in ATTR-CM and varies by genotype, while incorporation of LASr markedly improves detection of elevated filling pressure. These findings underscore the need for a personalized approach and precision therapy tailored to genotypical differences and comorbidities.