Patients with transthyretin amyloid cardiomyopathy may have preserved, mildly reduced, or reduced ejection fraction

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an often-overlooked form of heart failure with preserved ejection fraction (HFpEF). Previous studies have demonstrated that relatively high proportions of older patients with HFpEF have underlying ATTR-CM. However, while ATTR-CM should not be overlooked as a cause of HFpEF, it also should not be assumed that all patients with ATTR-CM present with HFpEF. Purpose To categorise patients with ATTR-CM from a large clinical trial by left ventricular ejection fraction (LVEF) at enrolment in order to describe the prevalence of HFpEF, HF with mildly reduced EF (HFmrEF), and HF with reduced EF (HFrEF). Methods The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) enrolled 441 patients with ATTR-CM, including both hereditary (ATTRv) and wild-type (ATTRwt) patients. In ATTR-ACT, all patients underwent echocardiography at enrolment using a standardised protocol, and all images were reviewed and analysed at an independent central laboratory. In this analysis of patient data at enrolment, all patients in ATTR-ACT were categorised by LVEF as: HFpEF (LVEF ≥50%), HFmrEF (LVEF 41–49%), or HFrEF (LVEF ≤40%). The proportions of patients in these LVEF categories in the sub-groups of race, sex, genotype, and disease severity (by NYHA class) were assessed, together with myocardial contraction fraction (MCF) in each category. Results In ATTR-ACT, there were 220 (50.5%) patients with HFpEF, 119 (27.3%) with HFmrEF, and 97 (22.3%) with HFrEF (Table). Five subjects with missing LVEF at enrolment were not categorized. Asian patients had the highest proportion with HFpEF, followed by White, then Black patients. The ATTRwt group had a higher proportion of patients with HFpEF than the ATTRv group. There were significant differences (as assessed by Chi-square test; P=0.0001) in the proportion of patients in each EF category between NYHA class I or II and NYHA class III patients. Median MCF was higher in NYHA class I/II (16.6%) than NYHA class III (14.8%) patients, and higher in patients with HFpEF compared with HFmrEF and HFrEF. Conclusions Not all patients with ATTR-CM have HFpEF. In this analysis of patients at enrolment in ATTR-ACT half had mildly reduced or reduced LVEF, with even higher proportions of reduced EF observed in Black patients, ATTRv patients, and patients with worse functional class (NYHA class III). These data demonstrate that ATTR-CM should be considered as a possible diagnosis in all patients with HF regardless of EF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer Table 1

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