No abstract

Fabry disease is a genetic disorder caused by the deficiency of a-galactosidase A, resulting in the lysosomal accumulation of glycosphingolipids. Fabry disease may result in cardiac, cerebral and renal complications. Cardiac abnormalities in patients with Fabry disease were first described in the 1960s. In the 1990s a form of Fabry disease confined to the heart was reported; however, this variant is extremely rare and a more appropriate concept is of cardiac predominance of the disease in some patients. Up to 60% of males with classic Fabry disease have cardiac abnormalities, including left ventricular hypertrophy, valvular dysfunction and conduction abnormalities. Recent data suggest that left ventricular mass and systolic function in patients with Fabry disease improve after 12 months of enzyme replacement therapy (ERT); however, many of the patients studied are relatively young and have mild cardiac abnormalities, suggesting that more research into the efficacy of ERT in older patients is necessary.Conclusion: Cardiac manifestations are common in patients with Fabry disease and are not confined to a 'cardiac variant' of the disease.

AimThe value of disease‐modifying therapies (such as tafamidis) in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) and severe heart failure symptoms has been debated. This study assessed long‐term all‐cause survival in patients with New York Heart Association (NYHA) class III symptoms in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) long‐term extension (LTE) study.Methods and resultsAt the baseline of ATTR‐ACT, 55/176 (31.3%) patients receiving tafamidis 80 mg and 63/177 (35.6%) receiving placebo had NYHA class III symptoms. After 30 months of treatment, patients could join an ongoing LTE study to receive open‐label tafamidis. In an interim analysis of the LTE study (August 2021), all‐cause mortality was lower among patients with NYHA class III symptoms who received continuous tafamidis in ATTR‐ACT and the LTE study (hazard ratio 0.64; 95% confidence interval 0.41–0.99; median follow‐up: 60 months), as compared with those who received placebo in ATTR‐ACT and tafamidis in the LTE study (median follow‐up: 56 months). Similar findings were observed in patients with NYHA class I/II symptoms at baseline (0.50; 0.35–0.73; tafamidis 80 mg n = 121; placebo n = 114; median follow‐up of 61 and 60 months, respectively).ConclusionWe observed reduced all‐cause mortality with continuous tafamidis treatment compared with delayed tafamidis treatment (placebo then tafamidis) in patients with NYHA class III symptoms at baseline over a median follow‐up of ∼5 years. These findings demonstrate the value of tafamidis treatment in patients with ATTR‐CM and severe heart failure symptoms, and emphasize the importance of early treatment.Clinical Trial Registrations: ClinicalTrials.gov NCT01994889 and NCT02791230.

Restrictive cardiomyopathy (RCM) is defined on the basis of the haemodynamic finding of restrictive ventricular physiology. However, restrictive ventricular pathophysiology is also a feature of other subtypes of cardiomyopathy, including hypertrophic cardiomyopathy (HCM). Clinically and aetiologically, there is an overlap between RCM and HCM with restrictive physiology. However, the clinical distinction between these two entities can be an important pointer towards the underlying aetiology. This review highlights the importance of the recognition of the clinical phenotype as the first step in the classification of cardiomyopathies