Chmielewski P, Michalak E, Kowalik I, Franaszczyk M, Sobieszczanska-Malek M, Truszkowska G, Stepien-Wojno M, Biernacka EK, Foss-Nieradko B, Lewandowski M, Oreziak A, Bilinska M, Kusmierczyk M, Tesson F, Grzybowski J, Zielinski T, Ploski R, Bilinska ZT.J Clin Med. 2020 May 12;9(5):E1443. doi: 10.3390/jcm9051443.PMID: 32408651 Free article.
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.
Figure 1 Distribution of LMNA variants in our study cohort. Legend: NLS, nuclear localization signal.
Figure 2 Diagnoses of probands and relatives at initial visit and last follow-up. Legend: CM: cardiomyopathy; DCM: dilated cardiomyopathy; HNDC: hypokinetic non-dilated cardiomyopathy.
Figure 3 Penetrance of cardiolaminopathy indicators. Legend: AVB: atrioventricular block; HF: heart failure; hs: highly sensitive; MVA: malignant ventricular arrhythmia; NT-proBNP: N-terminal pro-brain natriuretic peptide; SVA: supraventricular arrhythmia.
Figure 4 Kaplan–Meier lifelong HTX-free survival curves in cardiolaminopathy according to (a) sex and (b) mutation type. Legend: HTX: heart transplantation.
Figure 5 Kaplan–Meier lifelong MVA-free survival curves in cardiolaminopathy according to (a) sex and (b) mutation type. Legend: MVA: malignant ventricular arrhythmia.