Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths.
OBJECTIVE
Wild-type transthyretin amyloidosis (ATTRwt) is mostly considered a disease predominantly of elderly male, characterized by concentric LV hypertrophy, preserved LVEF, and low QRS voltages. We sought to describe the characteristics of a large cohort of ATTRwt patients to better define the disease.


RESULTS
Clinical findings of consecutive ATTRwt patients diagnosed at 2 centres were reviewed. ATTRwt was diagnosed histologically or non-invasively (LV hypertrophy ≥12 mm, intense cardiac uptake at 99mTc-DPD scintigraphy and AL exclusion). Mutations in TTR were excluded in all cases. The study cohort comprised 108 patients (78.6 ± 8 years); 67 (62%) diagnosed invasively and 41 (38%) non-invasively. Twenty patients (19%) were females. An asymmetric hypertrophy pattern was observed in 25 (23%) patients. Mean LVEF was 52 ± 14%, with 39 patients (37%) showing a LVEF < 50%. Atrial fibrillation (56%) and a pseudo-infarct pattern (63%) were the commonest ECG findings. Only 22 patients fulfilled QRS low-voltage criteria while 10 showed LV hypertrophy on ECG. Although heart failure was the most frequent profile leading to diagnosis (68%), 7% of individuals presented with atrioventricular block and 11% were diagnosed incidentally. Almost one third (35; 32%) were previously misdiagnosed.


CONCLUSIONS
The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.
Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.|Myocardial Biology Programme, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).
Esther
E
González-López
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Christian
C
Gagliardi
Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).
Fernando
F
Dominguez
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Cristina Candida
CC
Quarta
Department of Nuclear Medicine, Hospital Universitario Puerta de Hierro, Madrid, Spain.
F Javier
FJ
de Haro-Del Moral
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Agnese
A
Milandri
Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).|Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Clara
C
Salas
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Mario
M
Cinelli
Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).
Marta
M
Cobo-Marcos
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Massimiliano
M
Lorenzini
Myocardial Biology Programme, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).
Enrique
E
Lara-Pezzi
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Serena
S
Foffi
Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).
Luis
L
Alonso-Pulpon
Institute of Cardiology, University of Bologna and S Orsola-Malpighi Hospital, Bologna, Italy.
Claudio
C
Rapezzi
Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV).|Medical School, Francisco de Vitoria University, Madrid, Spain.
Pablo
P
Garcia-Pavia
D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000000981:diagnostic imaging / Q000473:pathology*; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D003951:Diagnostic Errors; D004164:Diphosphonates; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D008297:Male; D064847:Multimodal Imaging; D015609:Organotechnetium Compounds; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods
D004164:Diphosphonates; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C033905:technetium Tc 99m 1,1-diphosphonopropane-2,3-dicarboxylic acid
99mTc-DPD; Cardiac amyloidosis; Scintigraphy; Transthyretin; Wild-type