POSTER ABSTRACTS / RESUMOS DE POSTERS

 

P-03

Clinical and prognostic profile of patients with dilated cardiomyopathy caused by mutations in MYBPC3 gene

 

 

Alexandra Sousa¹; Paulo Canedo²; Brenda Moura³; Luís Lopes⁴; Olga Azevedo⁵; Sandra Amorim⁶; Francisco Rocha Gonçalves¹; José Carlos Machado²; José Silva-Cardoso⁶; Elisabete Martins¹

¹Faculty of Medicine, University of Porto, Porto
²Institute of Molecular Pathology and Immunology, University of Porto, Porto
³Regional Military Hospital nº1, Porto
⁴Garcia de Orta Hospital, Lisboa
⁵Alto Ave Hospital Center, Guimarães
⁶São João Hospital, Porto

E-mail: xanasousa81@gmail.com

 

 

Background: MYBPC3 mutations are frequent in patients (pts) with hypertrophic cardiomyopathy (HCM), representing 40–50% of all mutations. Mutations in this gene are also found in pts with dilated cardiomyopathy (DCM), accounting for approximately 2% of the cases, where knowledge of genotype- phenotype correlations remains sparse. We aimed to describe the clinical course of pts with DCM carrying mutations in MYBPC3 gene.

Methods: We evaluated 107 pts with idiopathic DCM (age ≤ 50 years) or familial DCM (irrespective of age). Detailed clinical data were obtained. Echocardiographic, ECG, Holter and CMR parameters were collected. Molecular analysis included LMNA/C, MYH7, MYBPC3, TNNT2, ACTC1, TPM1, CSRP3, TCAP, SGCD, PLN, MYL3, TNNI3, TAZ and LBD3 genes. Pts with mutations in MYBPC3 gene were comprehensively analyzed.

Results: Ten variants in MYBPC3 gene were found in nine (8.4%) pts (four men, mean age 52±12 years, six cases of familial DCM). None of the variants had been previously described in association with DCM, but six were associated with HCM (Asp75Asn, Gly278Glu, Gly279Ala, Glu441Lys, Arg495Gln and Glu619Lys). Mean age at diagnosis was 44±10 years and symptoms of heart failure (HF) were the initial manifestation in 7 pts. Five pts had previous hospitalization (two from HF and three from arrhythmic causes), two received an ICD and one a CRT device. In 3 pts there was history of heart transplant in a family member and in 2 there was family history of sudden death. Mean LVEDD was 67±3 mm, LVEF 32±10% and in 3 pts there was right ventricular function impairment. Three pts had AF, 5 LBBB and episodes of nonsustained VT (NSVT) were documented in 2. LGE was present also in 2 pts.

Three pts exhibited a particular dismal clinical course: a woman with c.1226+6T>C mutation, LVEDD 71 mm and LVEF 18%, AF, LBBB and NSVT, presented 3 HF-hospitalizations, had ICD implantation and eventually died of HF; a men with Arg495Gln mutation, had LVEED 67 mm and LVEF 32%, extensive LGE, a previous hospitalization from arrhythmic cause, presented aborted cardiac arrest and subsequent ICD implantation; a woman with Ala433Gly mutation presented in NYHA class III, LVEF 15%, LVEDV 212 mL/m2 and 10 previous HF-hospitalizations. On the other hand, one pts had two MYBPC3 variants (Glu441Lys+Gly279Ala) and another an additional mutation in TNNT2 gene (Ser275Phe) beyond MYBPC3 mutation (Arg44His): both were in NYHA class I and had no congestion; LVEF/LVEDD were 49%/61mm and 45%/51mm and neither had right ventricle impairment; the latter had AF and a previous arrhythmia-related hospitalization.

Conclusions: In our population, mutations in MYBPC3 gene appear to be more common than in previous series. Although most of the variants found were previously associated with HCM, a causative role also in DCM seems plausible. Carriers of mutations in MYBPC3 gene present a variable, but in general dismal, clinical course, with very severe outcome in some instances.