Abstract
Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.
Highlights
Dilated cardiomyopathy (DCM) is a major cause of heart failure (HF) and has a genetic basis in 40–50% of cases [1]
In patients with no history of sudden cardiac arrest (SCA) or sustained ventricular tachycardia, we evaluated the prognostic value of circulating cardiac biomarker concentrations, assessed during initial visit or in the time window ± 6 months with regard to occurrence of malignant ventricular arrhythmia (MVA) during the follow-up, and compared it with other established risk factors
MVA was defined as sudden cardiac death (SCD), cardiopulmonary resuscitation (CPR), or appropriate implantable cardioverter defibrillator (ICD) shock
Summary
Dilated cardiomyopathy (DCM) is a major cause of heart failure (HF) and has a genetic basis in 40–50% of cases [1]. There is growing evidence of distinct arrhythmogenic phenotype in DCM related to LMNA, SCN5A, PLN, RBM20, FLNC, and DSP mutations [2,3,4,5,6]. None of the studies involved baseline characteristics including circulating cardiac biomarkers. In 2005, a Canadian–Irish–Polish joint study showed the presence of LMNA mutations in 4.4% of consecutive DCM cases [14]. We found that 7.6% of 66 heart transplant (HTX) recipients and 9.1% of consecutive DCM patients referred for familial evaluation carry LMNA mutations [15]. We have identified subsequent 28 LMNA mutation carriers in the National Institute of Cardiology, Warsaw. We sought to assess the clinical characteristics including serum biomarkers, penetrance of abnormal clinical findings, and prognostic risk factors in all identified LMNA mutation carriers
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