Abstract Background Transthyretin amyloidosis (ATTR) results from mutations in the TTR gene (vATTR) or conformational changes in wild-type protein (wtATTR). Regarding TTR mutations, the Familial Amyloid Polyneuropathy phenotype is endemic in Portugal, Sweden and Japan, with the V30M being the most common pathogenic variant. Our goal is to characterize cardiac manifestations of V30M ATTR patients, particularly amyloid cardiomyopathy (CM). Methods We conducted a retrospective study including patients with TTR V30M mutation, with and without CM, consecutively observed at our center in Cardiology appointments in 2019 and followed for at least 5 years. Diagnostic criteria for ATTR-CM were considered according to ESC recommendations. Data on severe aortic stenosis, atrial fibrillation (Afib) and conduction abnormalities, were also collected. "Significant conduction disease" was considered in patients with a clear recommendation for pacemaker implantation or in those whose initial indication was uncertain but who eventually required more than 10% pacing. V30M ATTR-CM patients were compared to a cohort with wtATTR-CM. Results We enrolled a total of 248 TTR V30M patients, with a mean age of 54 years old, mostly male (53%) and with early onset disease (50 years) (68%). 49 (21%) patients fulfilled the criteria for ATTR-CM diagnosis. Significant electric conduction diseases were present in 31% of patients and were notably higher within the CM group (57% vs 25%, p0.001). Overall, among pacemaker carriers, only 61% (n=77) had a significant conduction disease. Afib was noted in 11% of the entire cohort, being significantly more frequent among patients with CM (31% vs 6%, p0.001). Severe aortic stenosis was rare, present in only 4 patients of the entire cohort. In comparison with a cohort of patients with wtATTR-CM (n=44), patients with V30M vATTR-CM were significantly younger and had more electric conduction abnormalities and orthostatic hypotension. On the other hand, AFib, systolic dysfunction and hypertension were less frequent, which parallelled with lower levels of NT-proBNP and troponin T (Table 1). Conclusion Our findings highlight the need for thorough cardiovascular evaluation in TTR V30M patients due to frequent conduction disease and CM. V30M ATTR-CM patients are younger, have more conduction abnormalities, and a lower prevalence of AFib compared to those with wtATTR-CM. Further prospective studies are needed to explore differences in CM between variant and wild-type cases.
Santos et al. (Sat,) studied this question.