Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction.

Abstract

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non-invasively using ^{99 m}Tc 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy-based diagnostic criteria. Our aim was to determine the prevalence of ATTR-CM in an undifferentiated HFpEF cohort with a DPD scintigraphy-based screening protocol.

Methods: Patients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60 years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant.

Results: Eighty-six subjects were prospectively enrolled: 56% female, mean age 77 ± 8 years, 63% New York Heart Association (NYHA) Class III and median N-terminal pro-brain natriuretic peptide (NT-proBNP) 1766 ng/L [inter-quartile range (IQR) 731-3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild-type ATTR-CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy-negative cohort, DPD scintigraphy-positive patients were older (86 ± 3 vs. 76 ± 8 years), more frequently male (16% vs. 2%, P = 0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12 mm; P = 0.002) and higher high-sensitivity troponin levels at diagnosis [78 ng/L (IQR 21-116) vs. 11 ng/L (IQR 9-17); P < 0.001].

Conclusions: In an undifferentiated HFpEF cohort, 8% were found to have wild-type ATTR-CM using a DPD scintigraphy-based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high-sensitivity troponin levels.