Brown, Matthew T.

AbstractLittle is known about the post heart transplantation management of extra cardiac manifestations in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR‐CM) in the new era of disease modifying treatment for ATTR amyloidosis. This is a retrospective study of all patients with hATTR‐CM associated with the Val142Ile variant who underwent heart transplantation (HT) from January 2014 to February 2022. All 10 patients with the Val142Ile mutation were successfully transplanted, with a 1 year survival post heart transplantation (HT) of 90%, comparable to an age, sex, and race matched cohort of patients transplanted for non‐amyloid indications. However, 4 (40%) of these patients developed progressive extracardiac manifestations requiring initiation of TTR silencer therapy with the small interfering RNA (siRNA) drug patisiran, which was well tolerated with no significant side effects in this population. We recommend formal neurologic evaluation and assessment of extracardiac manifestations annually as part of routine post‐transplant care, and disease modifying therapy, aimed at TTR stabilization or silencing, should be initiated in the context of previously untreated extracardiac manifestations or evidence of subclinical neuropathy to prevent progression.

AbstractBackgroundAs targeted treatments for amyloid transthyretin cardiomyopathy (ATTR‐CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter‐defibrillator (ICD) utilization, and their impact on survival.MethodsThis is a retrospective cohort study of 130 patients with ATTR‐CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation.ResultsOf 130 patients, 42 had wild‐type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR‐CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty‐two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699).ConclusionsHigh rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR‐CM patients with a high rate of systolic heart failure.