Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis

Abstract

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure in older individuals. We sought to characterize the natural history of ATTR-CM and compare outcomes and quality of life among patients with acquired and hereditary forms of the disease. Methods: We studied 711 patients with wild-type ATTR-CM, 205 with hereditary ATTR-CM associated with the V122I variant (V122I-hATTR-CM), and 118 with non-V122I-hATTR-CM at the UK National Amyloidosis Center between 2000 and 2017. Patients underwent prospective protocolized evaluations comprising assessment of cardiac parameters, functional status by 6-minute walk test, quality of life according to the Kansas City Cardiomyopathy Questionnaire, and survival. Hospital service usage pre- and postdiagnosis was established using English central health records in a subset of patients. Results: There was substantial diagnostic delay, with patients using hospital services a median (interquartile range) of 17 (9–27) times during the 3 years before diagnosis, by which time quality of life was poor; diagnosis of wild-type ATTR-CM was delayed >4 years after presentation with cardiac symptoms in 42% of cases. Patients with V122I-hATTR-CM were more impaired functionally ( P <0.001) and had worse measures of cardiac disease ( P <0.001) at the time of diagnosis, a greater decline in quality of life, and poorer survival ( P <0.001) in comparison with the other subgroups. Conclusions: ATTR-CM is an inexorably progressive and eventually fatal cardiomyopathy associated with poor quality of life. Diagnosis is often delayed for many years after symptoms develop. Improved awareness and wider use of recently validated diagnostic imaging methods are urgently required for patients to benefit from recent therapeutic developments.

Quality of life outcomes in APOLLO, the phase 3 trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

“…hATTR amyloidosis has a heterogeneous presentation, in which polyneuropathy, autonomic dysfunction and cardiac involvement most often coexist and result in a wide range of signs and symptoms that reduce QOL [3,4,[20][21][22]25,[49][50][51].…”

99mTc-aprotinin imaging in cardiac amyloidosis. Make an old tool new again?

“…4 ATTR amyloidosis is increasingly recognized as cardiomyopathy in elderly people, especially in men. 5 Amyloid in these cases has been derived from nonmutated, so-called wild-type TTR. ATTR amyloidosis can also sometimes be found as a hereditary disease, caused by a mutation in the TTR gene, often with a clinical picture dominated by polyneuropathy.…”

Regression of cardiac amyloid load documented by cardiovascular magnetic resonance in a patient with hereditary amyloidosis

“…Notably, from the 186 patients in the non-cardiac mutation group at baseline, only two were alive at 6 years [6]. In another longitudinal study, patients with a non-Val122Ile amyloid cardiomyopathy had the highest median survival (69 months) when compared to Val122Ile or wtATTR cardiomyopathy (31 and 57 months, respectively) [4].…”

“…Interestingly, the previous thickening of the atrial septum had almost completely disappeared (Figs. 3,4).…”

“…Hereditary ATTR-associated cardiomyopathy usually manifests with a hypertrophic/restrictive phenotype, conduction disease and arrhythmias leading to heart failure, reduced quality of life and finally to death [4]. A non-invasive diagnosis of cardiac amyloidosis is possible either by multi-parametric CMR or repurposed bone scintigraphy [3,5].…”