Point mutations in mitochondrial DNA of patients with alcoholic cardiomyopathy

Teragaki, Masakazu; Takeuchi, Kazuhide; Toda, Iku; Yoshiyama, Minoru; Akioka, Kaname; Tanaka, Masashi; Yoshikawa, Junichi

doi:10.1007/pl00007268

Cited by 12 publications

(6 citation statements)

References 22 publications

(36 reference statements)

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“…In both cultured cells and in chronic feeding experiments, elevated ethanol presentation increased mtDNA damage, findings that are consistent with previous reports in alcoholic patients (Teragaki et al, 2000). In contrast, mitochondrial copy number was decreased only in cultured cardiomyocytes exposed to 100 mM ethanol, but no changes were observed in the left ventricle.…”

Section: Discussionsupporting

confidence: 92%

Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases

Laurent

Mathew

Mitry

et al. 2014

Alcohol and Alcoholism

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Chronic ethanol feeding compromised cardiovascular and mitochondrial function as a result of a decline in mtDNA integrity that was in part the consequence of mitochondrial topoisomerase dysfunction. Understanding the regulation of the mitochondrial topoisomerases is critical for protection of mtDNA, not only for the management of alcoholic cardiomyopathy, but also for the many other clinical treatments that targets the topoisomerases in the alcoholic patient.

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Section: Discussionsupporting

confidence: 92%

Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases

Laurent

Mathew

Mitry

et al. 2014

Alcohol and Alcoholism

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“…Genetic predisposition or the presence of synergistic cardiovascular factors such as hypertension, nutritional deficiencies, or arrhythmias could play a role. 94 …”

Section: Epidemiology and Prognosismentioning

confidence: 99%

“…In patients with alcoholic cardiomyopathy, total abstinence is recommended (Level of Evidence C). [88][89][90][91]94,95 Cocaine-related Cardiomyopathy…”

Section: Key Management Strategies For Alcoholic Cardiomyopathymentioning

confidence: 99%

Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association

Bozkurt¹,

Colvin²,

Cook³

et al. 2016

Circulation

603

663

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CLINICAL STATEMENTS AND GUIDELINEST he intent of this American Heart Association (AHA) scientific statement is to summarize our current understanding of dilated cardiomyopathies. There is special emphasis on recent developments in diagnostic approaches and therapies for specific cardiomyopathies. Recommendations in this document are based on published studies, published practice guidelines from the American College of Cardiology (ACC)/AHA 1 and other organizations, 2,3 and the multidisciplinary expertise of the writing group. Existing evidence in epidemiology, classification, diagnosis, and management of specific cardiomyopathies is usually derived from nonrandomized observational studies, registries, case reports, or expert opinion based on clinical experience, not large-scale randomized clinical trials or systematic reviews. Therefore, in this document, rather than using the standard ACC/AHA classification schema of recommendations and level of evidence, 4 we have included key management strategies at the end of each section and categorized our recommendations according to the level of consensus. Although the format of our recommendations might resemble the ACC/AHA classification of recommendations used in the ACC/AHA practice guidelines, because of the preponderance of expert opinion or level of evidence C evidence in our document, we elected to use different terminology to provide a distinction from the practice guidelines, in which stronger levels and quality of evidence with randomized clinical trials or meta-analyses are usually present. 4 The levels of evidence follow the AHA and ACC methods of classifying the level of certainty of the treatment effect. 4 DEfINITIoN of DILATED CArDIoMyopAThyThe term dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders that are characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. 5 In clinical practice, the pathogenesis of heart failure (HF) has often been placed into 2 categories: ischemic and nonischemic cardiomyopathy. The term nonischemic cardiomyopathy has been interchangeably used with DCM. Although this approach might be practical, it fails to recognize that nonischemic cardiomyopathy can include cardiomyopathies caused by volume or pressure overload (such as hypertension or valvular heart disease) that are not conventionally accepted under the definition of DCM. 1,5 Again, in general practice and clinical research trials, the term ischemic cardiomyopathy is defined as cardiomyopathy caused by ischemic heart disease. Current use of ischemic cardiomyopathy terminology implies ventricular dilation and depressed myocardial contractility caused by ischemia or infarction. CLASSIfICATIoN of CArDIoMyopAThIESThe first classification on this topic categorized cardiomyopathies as heart muscle diseases with dilated (DCM), hypertrophic, restrictive, arrhythmogenic right ventricular (ARVC), or nonclassifiable cardiomyopathy in 1980. 5 Subse...

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“…In particular, not all individuals with high alcohol intake develop ACM, and this heterogeneity in response indicates differences in underlying susceptibility, likely both genetic and environmental. However, studies of heritable contributors to ACM are currently limited 7 , 8 . Prognosis in ACM is poor, but is considered more favorable than DCM generally, with recovery observed in up to one-third of cases, especially when alcohol intake is reduced (3) .…”

mentioning

confidence: 99%

Genetic Etiology for Alcohol-Induced Cardiac Toxicity

Ware

Amor-Salamanca

Tayal

et al. 2018

Journal of the American College of Cardiology

208

120

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BackgroundAlcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol.ObjectivesThis study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity.MethodsThe authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM.ResultsVariants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10−5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: −2.3% to −15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients.ConclusionsTTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.

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Point mutations in mitochondrial DNA of patients with alcoholic cardiomyopathy

Cited by 12 publications

References 22 publications

Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases

Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases

Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association

Genetic Etiology for Alcohol-Induced Cardiac Toxicity

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