Prevalence and prognostic impact of valvular heart disease in transthyretin cardiac amyloidosis

Significant valvular heart disease (VHD) is associated with adverse prognosis in transthyretin amyloidosis cardiomyopathy (ATTR-CM). However, data is limited to isolated VHD. We aimed at evaluating the difference in outcome between isolated and multiple VHD, and particularly with and without aortic stenosis (AS). Patients with ATTR-CM were retrospectively included in a multicentric registry. The endpoint was a composite of heart failure hospitalizations and all-cause death. Of the 694 patients (mean age 75 ± 13 years,74%male), 302(44%) presented with significant VHD. Of these, 98 had VHD including AS (isolated AS in 45%;multiple VHD with AS in 55%), while 204 had VHD without AS (isolated in 64%, multiple VHD in 36%). During a median follow-up of 22(8–38) months, 217(31%) patients reached the endpoint. Significant VHD was associated with worse outcomes than no-VHD (log-rank p < 0.001; HR:3.275; 95%CI (2.472–4.337), remaining significant after adjustment (HR2.006 (1.193–3.047);p = 0.007). Stratification by the presence of AS, and according to isolated or multiple VHD, revealed that isolated significant AS ((HR: 2.462; 95%CI (1.233–4.917); p = 0.011), and multiple VHD including significant AS, had the highest risk for adverse outcomes ((HR: 3.385; 95%CI (1.744–6.573);p < 0.001). In ATTR-CM, significant VHD is strongly associated with poor prognosis, with the highest risk for adverse events in significant multiple VHD including AS.