title: Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: González-López
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Gallego-Delgado
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Guzzo-Merello
authors.affiliation: Department of Nuclear Medicine, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: de Haro-Del Moral
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cobo-Marcos
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Robles
authors.affiliation: Department of Biochemistry, Hospital Universitario Puerta de Hierro, Madrid, Spain Department of Biochemistry, Biomedical Research Institute 'Alberto Sols', Medicine UAM-CSIC, Madrid, Spain Rare Diseases Biomedical Research Centre (CIBERER), Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Bornstein
authors.affiliation: Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Salas
authors.affiliation: Myocardial Biology Programme, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lara-Pezzi
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Alonso-Pulpon
authors.affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla, 2, Majadahonda, Madrid 28222, Spain Myocardial Biology Programme, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain pablogpavia@yahoo.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Pavia
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004164:Diphosphonates; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds; D011446:Prospective Studies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013318:Stroke Volume / Q000502:physiology
chemical_list: D004164:Diphosphonates; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C033905:technetium Tc 99m 1,1-diphosphonopropane-2,3-dicarboxylic acid
keywords: 99mTc-DPD scintigraphy; Cardiac amyloidosis; Diastolic heart failure; Heart failure with preserved ejection fraction; Senile systemic amyloidosis; Transthyretin