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Aims: To evaluate the effect of long‐term tafamidis treatment on health‐related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) and long‐term extension (LTE) study. Methods and results: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ‐OS) and clinical summary (KCCQ‐CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR‐ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR‐ACT and tafamidis for 30 months in the LTE study. In ATTR‐ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6‐ to 7‐point reduction in least squares (LS) mean (standard error) KCCQ‐OS and KCCQ‐CS scores at month 30 (−6.25 [1.53] and −7.48 [1.39]), with little or no further decline over the next 30 months (−5.92 [1.77] and −9.21 [1.88] at month 60). Patients who received placebo in ATTR‐ACT had a 20‐point reduction in LS mean KCCQ‐OS and KCCQ‐CS scores at month 30 (−19.60 [1.94] and −19.90 [2.01]), but the decline slowed after initiating tafamidis (−24.70 [3.04] and −25.30 [3.36] at month 60). Conclusion: Tafamidis reduced HRQoL decline in patients with ATTR‐CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR‐ACT, tafamidis reduced the decline in HRQoL during the LTE study. [ABSTRACT FROM AUTHOR]

Aim: Epidemiology of wild‐type transthyretin cardiac amyloidosis (ATTRwt‐CA) remains poorly defined. A better characterization of pathways leading to ATTRwt‐CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt‐CA diagnosis, and their potential association with survival. Methods and results: This was a retrospective study of patients diagnosed with ATTRwt‐CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt‐CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all‐cause mortality as endpoint. Overall, 1281 ATTRwt‐CA patients were included in the study. The diagnostic pathway leading to ATTRwt‐CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III–IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III–IV and some comorbidities but not the HF pathway were independently associated with worse survival. Conclusions: Half of contemporary ATTRwt‐CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself. [ABSTRACT FROM AUTHOR]

Aims: Hereditary (ATTRv) and wild‐type (ATTRwt) transthyretin amyloidosis are severe and fatal systemic diseases, characterised by amyloid fibrillar accumulation principally in the heart or peripheral nerves (or both). Since 2012, tafamidis has been used in France to treat patients with ATTRv with neuropathy (alone or combined with cardiomyopathy). Recently, the Phase III ATTR‐ACT trial showed that tafamidis decreased the relative risk of mortality in ATTR amyloidosis with cardiomyopathy. The aims of this study were to assess the clinical characteristics of ATTR amyloidosis in a real‐life population in comparison to the population included in the ATTR‐ACT trial and to assess the impact of tafamidis treatment on major cardiovascular outcome (MCO)‐free survival time without cardiac decompensation, heart transplant, or death. Methods and results: From June 2008 to November 2018, 648 patients with ATTR amyloidosis (423 ATTRwt and 225 ATTRv) consecutively referred to the French Referral Center for cardiac amyloidosis were included. A total of 467 (72%) patients matched the inclusion criteria of the ATTR‐ACT trial. For the 631 patients with cardiomyopathy, tafamidis treatment was associated with a longer median MCO‐free survival time (n = 98): 1565 (1010–2400) days vs. 771 (686–895) days without treatment (log‐rank P < 0.001). This association was confirmed after considering confounding factors (age at inclusion, N‐terminal pro‐B‐type natriuretic peptide and amyloidosis type) with a propensity score (hazard ratio 0.546; P = 0.0132). Conclusion: In a large cohort of ATTRwt and ATTRv patients, representative of the inclusion criteria of the ATTR‐ACT trial, the present results show an association between tafamidis treatment and a lower occurrence of cardiovascular outcomes in a real‐life population. [ABSTRACT FROM AUTHOR]

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild-type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin-3-gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided. [ABSTRACT FROM AUTHOR]