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Journal of Translational Medicine Jul 2023Dilated cardiomyopathy (DCM) is one of the most frequent causes of heart failure and heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx...
BACKGROUND
Dilated cardiomyopathy (DCM) is one of the most frequent causes of heart failure and heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx remains to be further studied. This study aimed to characterize the genetic basis of DCM HTx in the Chinese population.
METHODS
In total, 208 unrelated DCM patients who underwent HTx at Fuwai Hospital between June 2004 and June 2017 were included in this study. Whole-exome sequencing (WES) was performed for all patients. Gene burden analysis, variant classification, and genotype-phenotype correlation analysis were subsequently performed.
RESULTS
After completing the bioinformatics analysis, gene burden analysis suggested that titin (TTN), filamin C (FLNC) and lamin A/C (LMNA) were significantly enriched with rare protein-altering variants. The frequencies of TTN and FLNC truncating variants in our cohort were 18.8% and 8.7%, respectively. Among the 165 rare variants in high evidence DCM-related genes, 27 (16.4%) and 59 (35.8%) were interpreted as pathogenic (P) and likely pathogenic (LP), respectively. In addition, 41 (47.7%) and 16 (18.6%) of these 86 P/LP variants are located in TTN and FLNC, respectively. The FLNC group contained more patients with NYHA class IV than the P/LP-negative group (FLNC, 16/18 vs. P/LP-negative, 81/123, P = 0.049).
CONCLUSIONS
Based on WES, we provided a primary genetic spectrum of DCM patients undergoing HTx in the Chinese population. TTN and FLNC harbour the most P/LP variants. FLNC truncation may lead to severe clinical symptoms in DCM patients.
Topics: Humans; Cardiomyopathy, Dilated; East Asian People; Exome Sequencing; Genetic Association Studies; Heart Transplantation; Mutation
PubMed: 37461109
DOI: 10.1186/s12967-023-04282-5 -
JACC. Heart Failure Feb 2024
Topics: Humans; Female; Heart Failure; Cardiomyopathy, Dilated; Heart Transplantation; Ventricular Function, Left
PubMed: 38326001
DOI: 10.1016/j.jchf.2023.11.013 -
European Journal of Heart Failure Jul 2020The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and... (Review)
Review
The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non-specific in DCM, the recently acquired knowledge of the genotype-phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG-based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves.
Topics: Cardiomyopathy, Dilated; Echocardiography; Electrocardiography; Heart Failure; Humans; Risk Assessment
PubMed: 32243666
DOI: 10.1002/ejhf.1815 -
Praxis Aug 2022Cardiomyopathies are myocardial disorders with a structurally and functionally abnormal heart muscle. In this review, we describe pathophysiological aspects, clinical... (Review)
Review
Cardiomyopathies are myocardial disorders with a structurally and functionally abnormal heart muscle. In this review, we describe pathophysiological aspects, clinical presentation, diagnosis, risk stratification and therapeutical concepts of the three most common forms of cardiomyopathy: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic cardiomyopathy (ACM).
Topics: Cardiomyopathies; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Humans; Myocardium
PubMed: 35975415
DOI: 10.1024/1661-8157/a003912 -
European Heart Journal. Cardiovascular... Sep 2022
Topics: Cardiomyopathies; Cardiomyopathy, Dilated; Citrus sinensis; Fibrosis; Phenotype
PubMed: 35900249
DOI: 10.1093/ehjci/jeac156 -
Journal of Cardiac Failure Nov 2021Substance use is common among those with heart failure (HF) and is associated with worse clinical outcomes. Alcohol, tobacco, cannabis, and cocaine are commonly abused... (Review)
Review
Substance use is common among those with heart failure (HF) and is associated with worse clinical outcomes. Alcohol, tobacco, cannabis, and cocaine are commonly abused substances that can contribute to the development and worsening of HF. Heavy alcohol consumption can lead to dilated cardiomyopathy, whereas moderate intake may decrease incident HF. Tobacco increases the risk of HF through coronary artery disease and coronary artery disease-independent mechanisms. Continued smoking worsens outcomes for those with HF and cessation is associated with an improved risk of major adverse cardiac events. Cannabis has complex interactions on the cardiovascular system depending on the method of consumption, amount consumed, and content of cannabinoids. Delta-9-tetrahydrocannabinol can increase sympathetic tone, cause vascular dysfunction, and may increase the risk of myocardial infarction. Cannabidiol is cardioprotective in preclinical studies and is a potential therapeutic target. Cocaine increases sympathetic tone and is a potent proarrhythmogenic agent. It increases the risk of myocardial infarction and can also lead to a dilated cardiomyopathy. The use of beta-blockers in those with HF and cocaine use is likely safe and effective. Future studies are needed to further elucidate the impact of these substances both on the development of HF and their effects on those who have HF.
Topics: Cardiomyopathy, Dilated; Heart; Heart Failure; Humans; Myocardial Infarction; Pharmaceutical Preparations
PubMed: 34133967
DOI: 10.1016/j.cardfail.2021.05.023 -
Journal of the American College of... Jun 2022
Topics: Cardiomyopathy, Dilated; Humans; Phenotype
PubMed: 35654494
DOI: 10.1016/j.jacc.2022.04.008 -
Circulation. Genomic and Precision... Aug 2023
Topics: Humans; Cardiomyopathy, Dilated; Prevalence; Arrhythmias, Cardiac; Myocardium; Diagnostic Techniques and Procedures; Protein Serine-Threonine Kinases
PubMed: 37325914
DOI: 10.1161/CIRCGEN.123.004207 -
Genome Medicine Sep 2023Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular...
BACKGROUND
Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.
METHODS
We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.
RESULTS
Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.
CONCLUSIONS
Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.
Topics: Humans; Animals; Dogs; Cardiomyopathy, Dilated; Homeostasis; Models, Animal; Phenotype; Risk Factors
PubMed: 37723491
DOI: 10.1186/s13073-023-01221-3 -
International Heart Journal 2022Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain... (Meta-Analysis)
Meta-Analysis
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.
Topics: Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Female; Humans; Male; Prognosis; Sex Factors
PubMed: 35095074
DOI: 10.1536/ihj.20-448