Heart transplantation as the method of treatment of the progressive cardiomyopathy in patients with primary muscular dystrophy
Abstract
Primary muscular dystrophies is a heterogeneous group of inherited disorders characterized by progressive weakness and degeneration of skeletal muscles. Proportion of the patients with primary myopathies in the cohort of the adult DCM patients is limited (in our register of 220 patients with DCM syndrome – 3.6%), these patients are characterized by young age and often by severe progressive course of
the disease. Genotype-phenotype correlations, principles of risk stratification and management of such
patients are clearly not outlined; few data available on successful heart transplantation in these patients
and its place in their treatment.
Aim. To analyze the clinical features of the cardiomyopathy in patients with genetically verified and
unspecified primary myopathies and the role of heart transplantation in treatment of cardiomyopathy.
Material and methods. The study included 9 patients from 8 unrelated families, 5 males and 4 females, mean age 31.4±13.8 years (from 16 y.o. to 63 y.o.) with a combination of cardiomyopathy and
skeletal myopathy and/or verified pathogenic mutations in the LMNA, EMD, and DES genes. Clinical and
instrumental investigations included: CK blood level, the detection of antibodies to various heart antigens by indirect ELISA, the PCR-based detection of DNA of cardiotropic viruses in the blood and myocardium, echocardiography, daily monitoring of the ECG by Holter; additionally – multi-layer spiral heart CT,
MRI, electroneuromyography, neurologic examination, right ventricular endomyocardial biopsy, explanted
heart examination, skeletal muscle biopsy, and autopsy. Genetic counseling was performed in all patients.
The genetic study included direct Sanger sequencing and semiconductor sequencing on the PGM IonTorrent platform of the coding and adjacent intronic regions of the LMNA, EMD, and DES genes, and semiconductor sequencing of 57 gene panels with AmpliSeq oligoprimers.
Results. Pathogenic mutations were detected in 7 out of 9 patients. Symptoms of skeletal myopathy
in the most of cases preceded the appearance of the first manifestations of cardiomyopathy. Almost in all
patients diasease manifested with the rhythm and conduction disturbances. Detailed picture of DCM was
revealed by EchoCG in 6 patients. A significant increase of the antibodies level against various heart structures was detected in 5 patients. Three male patients had died, and three patients successfully underwent
heart transplantation. Only 3 women are alive without transplantation, two of them have implanted devices
(PM and CRT-D).
Discussion. Pathogenic mutations were verified in 77.8% of patients in three genes – LMNA, EMD, and
DES, heart transplantation was successfully performed in each of these subgroups. Overlapping myocarditis
is a deterioration prognostic factor in various myopathies.
Conclusions. Cardiomyopathy in the myopathy has a steadily progressing course and poor prognosis.
By the time of 9 months of the total end point "death + transplantation" was reached by 66.7% of patients, the mortality was 33,3%. The female gender was proved to be a favorable prognostic sign.
Keywords:heart transplantation, dilated cardiomyopathy, laminopathy, emerinopathies, desminopathies, progressive myopathies, primary cardiomyopathies
Clin. Experiment. Surg. Petrovsky J. 2017; 5 (3): 34–48.
DOI: 10.24411/2308-1198-2017-00043
Received: 20.06.2017. Accepted: 14.07.2017.
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