Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction

[Aims]: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes.Wild-type transthyretin (TTR) amyloidosis (ATTRwt) is an underdiagnosed cause of HFpEF that might benefit from new specific treatments. ATTRwt can be diagnosed non-invasively by mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (mTc-DPD) scintigraphy. We sought to determine the prevalence of ATTRwt among elderly patients admitted due to HFpEF. [Methods and results]: We prospectively screened all consecutive patients .60 years old admitted due to HFpEF [left ventricular (LV) ejection fraction .50%] with LV hypertrophy (.12mm).All eligible patientswere offered a mTc-DPD scintigraphy. The study included 120 HFpEF patients (59% women, 82+8 years). A total of 16 patients (13.3%; 95% confidence interval: 7.2.19.5) showed a moderate-to-severe uptake on the mTc-DPD scintigraphy. All patients with a positive scan underwent genetic testing of the TTR gene, and no mutationswere found. An endomyocardial biopsywasperformed in four patients, confirmingATTRwt inall cases. There were no differences in age, gender, hypertension, diabetes, coronary artery disease, or atrial fibrillation between ATTRwt patients and patients with other HFpEF forms. Although patients with ATTRwt exhibited higher median N-terminal pro-brain natriuretic peptide (6467 vs. 3173 pg/L; P . 0.019), median troponin I (0.135 vs. 0.025 mg/L; P, 0.001), mean LV maximal wall thickness (17+3.4 vs. 14+2.5 mm; P . 0.001), rate of pericardial effusion (44 vs. 19%; P . 0.047), and rate of pacemakers (44 vs. 12%; P . 0.004), clinical overlap between ATTRwt and other HFpEF forms was high. [Conclusion]: ATTRwt is an underdiagnosed disease that accounts for a significant number (13%) of HFpEF cases. The effect of emerging TTR-modifying drugs should be evaluated in these patients.This work was partially supported by Pfizer Inc. through an Investigator Initiated Research Grant.Peer Reviewe