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Multicenter Study
. 2013 Dec;6(6):424-8.
doi: 10.1111/cts.12116. Epub 2013 Oct 3.

Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy

Marco Merlo  1 , Gianfranco Sinagra, Elisa Carniel, Dobromir Slavov, Xiao Zhu, Giulia Barbati, Anita Spezzacatene, Federica Ramani, Ernesto Salcedo, Andrea Di Lenarda, Luisa Mestroni, Matthew R G Taylor; Familial Cardiomyopathy Registry
Affiliations
Multicenter Study

Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy

Marco Merlo et al. Clin Transl Sci. 2013 Dec.

Abstract

Background: In dilated cardiomyopathy (DCM), the clinical and prognostic implications of rare variants in sarcomeric genes remain poorly understood. To address this question, we analyzed the outcome of rare sarcomeric gene variants in patients enrolled in our Familial Cardiomyopathy Registry.

Methods: DCM families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3, TNNT2, and TTN were identified. Genotype-phenotype association analysis was performed, and long-term survival-free from death or heart transplant was compared between carriers and noncarriers.

Results: We found 24 rare variants (3 in MYH6, 3 in MYH7, 3 in MYBPC3, 2 in TNNT2, and 13 in TTN) affecting 52 subjects in 25 families. The phenotypes of variant carriers were severe (3 sudden deaths, 6 heart failure deaths, 8 heart transplants, 2 ventricular fibrillations). There was no difference in the overall long-term survival between carriers and the 33 noncarriers (p = 0.322). However after 50 years of age, the combined endpoint of death or transplant was decreased in carriers as compared to noncarriers (p = 0.026).

Conclusions: Patients with DCM carrying rare variants in sarcomeric genes manifest a poorer prognosis as compared to noncarriers after the age of 50 years. These data further support the role of genetic testing in DCM for risk stratification.

Keywords: cardiomyopathy; genes; genetics; molecular genetics; phenotyping; prognosis.

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Figures

Figure 1
Figure 1
Comparison of long‐term natural history between 52 sarcomeric genes (MYH6, MYH7, MYBPC3, TNNT2, and TTN) rare variant carriers and noncarriers population (33 patients). Follow‐up from birth to end‐point/last follow‐up evaluation. Survival rates (as percentages) are provided at ages 25, 50, and 75 years. D/HTx: death or heart transplant.
Figure 2
Figure 2
Comparison of long‐term natural history between 25 probands carrying sarcomeric genes (MYH6, MYH7, MYBPC3, TNNT2, and TTN) rare variant carriers and noncarriers population (33 probands). Follow‐up from birth to end‐point/last follow‐up evaluation. Survival rates (as percentages) are provided at ages 25, 50, and 75 years. D/HTx = death or heart transplant.
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