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

Eur Heart J. 2015 Oct 7;36(38):2585-94. doi: 10.1093/eurheartj/ehv338. Epub 2015 Jul 28.


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 (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-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 (≥12 mm). All eligible patients were offered a (99m)Tc-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 (99m)Tc-DPD scintigraphy. All patients with a positive scan underwent genetic testing of the TTR gene, and no mutations were found. An endomyocardial biopsy was performed in four patients, confirming ATTRwt in all 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 µg/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.

Keywords: 99mTc-DPD scintigraphy; Cardiac amyloidosis; Diastolic heart failure; Heart failure with preserved ejection fraction; Senile systemic amyloidosis; Transthyretin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid Neuropathies, Familial / complications*
  • Amyloid Neuropathies, Familial / diagnostic imaging
  • Amyloid Neuropathies, Familial / physiopathology
  • Cross-Sectional Studies
  • Diphosphonates
  • Echocardiography
  • Electrocardiography
  • Female
  • Genotype
  • Heart Failure / diagnostic imaging
  • Heart Failure / etiology*
  • Heart Failure / physiopathology
  • Humans
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / physiopathology
  • Length of Stay
  • Male
  • Middle Aged
  • Organotechnetium Compounds
  • Prospective Studies
  • Radionuclide Imaging
  • Radiopharmaceuticals
  • Stroke Volume / physiology


  • Diphosphonates
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium Tc 99m 1,1-diphosphonopropane-2,3-dicarboxylic acid

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related