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Current Heart Failure Reports Oct 2020This review aims to give an update on recent findings related to the cardiac splicing factor RNA-binding motif protein 20 (RBM20) and RBM20 cardiomyopathy, a form of... (Review)
Review
PURPOSE OF REVIEW
This review aims to give an update on recent findings related to the cardiac splicing factor RNA-binding motif protein 20 (RBM20) and RBM20 cardiomyopathy, a form of dilated cardiomyopathy caused by mutations in RBM20.
RECENT FINDINGS
While most research on RBM20 splicing targets has focused on titin (TTN), multiple studies over the last years have shown that other splicing targets of RBM20 including Ca/calmodulin-dependent kinase IIδ (CAMK2D) might be critically involved in the development of RBM20 cardiomyopathy. In this regard, loss of RBM20 causes an abnormal intracellular calcium handling, which may relate to the arrhythmogenic presentation of RBM20 cardiomyopathy. In addition, RBM20 presents clinically in a highly gender-specific manner, with male patients suffering from an earlier disease onset and a more severe disease progression. Further research on RBM20, and treatment of RBM20 cardiomyopathy, will need to consider both the multitude and relative contribution of the different splicing targets and related pathways, as well as gender differences.
Topics: Cardiomyopathy, Dilated; DNA; DNA Mutational Analysis; Humans; Mutation; Myocytes, Cardiac; RNA-Binding Proteins
PubMed: 32789749
DOI: 10.1007/s11897-020-00475-x -
European Journal of Heart Failure Jul 2022
Topics: Cardiomyopathy, Dilated; Heart Failure; Humans; Stroke Volume
PubMed: 35717623
DOI: 10.1002/ejhf.2586 -
Current Heart Failure Reports Oct 2022Myocarditis is a disease caused by inflammation of the heart that can progress to dilated cardiomyopathy, heart failure, and eventually death in many patients. Several... (Review)
Review
PURPOSE OF REVIEW
Myocarditis is a disease caused by inflammation of the heart that can progress to dilated cardiomyopathy, heart failure, and eventually death in many patients. Several etiologies are implicated in the development of myocarditis including autoimmune, drug-induced, infectious, and others. All causes lead to inflammation which causes damage to the myocardium followed by remodeling and fibrosis. This review aims to summarize recent findings in biomarkers for myocarditis and highlight the most promising candidates.
RECENT FINDINGS
Current methods of diagnosing myocarditis, including imaging and endomyocardial biopsy, are invasive, expensive, and often not done early enough to affect progression. Research is being done to find biomarkers of myocarditis that are cost-effective, accurate, and prognostically informative. These biomarkers would allow for earlier screening for myocarditis, as well as earlier treatment, and a better understanding of the disease course for specific patients. Early diagnosis of myocarditis with biomarkers may allow for prompt treatment to improve outcomes in patients.
Topics: Biomarkers; Cardiomyopathy, Dilated; Heart Failure; Humans; Inflammation; Myocarditis; Myocardium
PubMed: 35913661
DOI: 10.1007/s11897-022-00569-8 -
Annals of Nutrition & Metabolism 2022Dilated cardiomyopathy (DCM) is the most common form of heart muscle disease characterized by progressive dilatation and ventricular dysfunction. Metabolomics is an... (Review)
Review
BACKGROUND
Dilated cardiomyopathy (DCM) is the most common form of heart muscle disease characterized by progressive dilatation and ventricular dysfunction. Metabolomics is an emerging and powerful discipline that provides a global information on the phenotype of mammalian systems via the study of endogenous and exogenous metabolites in cells, tissues, and biofluids. These studies aid in the identification of biomarkers to prevent diseases in later life or help to early detect onset of diseases as well as aiding in the elucidation of disease mechanisms.
SUMMARY
Metabolomics provides a unique opportunity to discover novel biomarkers for DCM. This review demonstrates evidence of metabolite-based biomarkers useful for predicting, diagnosing, and monitoring therapeutic interventions of DCM. Key metabolites identified as potential biomarkers for diagnosing DCM include acylcarnitines, succinic acid, malate, methylhistidine, aspartate, methionine, and phenylalanine. In terms of differentiating DCM from ischemic cardiomyopathy, potential biomarkers including 1-pyrroline-2-carboxylate, norvaline, lysophosphatidylinositol (16:0/0:0), phosphatidylglycerol, fatty acid esters of hydroxy fatty acid, and phosphatidylcholine were identified. Acylcarnitines, isoleucine and linoleic acid, and tryptophan were the main biomarkers to monitor treatment response to DCM. Mapping metabolites to metabolic pathways revealed dysregulation of branch-chain amino acid, glycolysis, tricarboxylic acid cycle, and triacylglycerol and pentose phosphate metabolism, which have the therapeutic potential for DCM. This review shows several limitations including the use of small sample sizes, lack of interpretation of age and sex differences in most studies, and the fact that studies have so far been limited to case-control study designs.
KEY MESSAGES
Metabolites have close proximity to disease phenotype. With recent advances in metabolomics field, potential biomarkers for DCM have been identified based on studies using different biological and metabolomics technologies. However, multicenter studies with larger populations that will lead to validation of these identified biomarkers to enable their clinical translation and utilization are still needed.
Topics: Animals; Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Female; Humans; Linoleic Acid; Male; Mammals; Metabolomics
PubMed: 35472668
DOI: 10.1159/000524722 -
Cells Oct 2021Ventricular arrhythmias contribute significantly to morbidity and mortality in patients with heart failure (HF). Pathomechanisms underlying arrhythmogenicity in patients... (Review)
Review
Ventricular arrhythmias contribute significantly to morbidity and mortality in patients with heart failure (HF). Pathomechanisms underlying arrhythmogenicity in patients with structural heart disease and impaired cardiac function include myocardial fibrosis and the remodeling of ion channels, affecting electrophysiologic properties of ventricular cardiomyocytes. The dysregulation of ion channel expression has been associated with cardiomyopathy and with the development of arrhythmias. However, the underlying molecular signaling pathways are increasingly recognized. This review summarizes clinical and cellular electrophysiologic characteristics observed in dilated cardiomyopathy (DCM) with ionic and structural alterations at the ventricular level. Furthermore, potential translational strategies and therapeutic options are highlighted.
Topics: Animals; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Electrophysiological Phenomena; Epigenesis, Genetic; Humans; Translational Research, Biomedical; Ventricular Remodeling
PubMed: 34685747
DOI: 10.3390/cells10102767 -
BMC Endocrine Disorders Jun 2021Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its...
BACKGROUND
Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia.
METHODS
An institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared at p < 0.05.
RESULTS
Mean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89-38.16, p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04-7.15, p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning β-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery.
CONCLUSIONS
In developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.
Topics: Adolescent; Adult; Antithyroid Agents; Cardiomyopathy, Dilated; Cross-Sectional Studies; Developing Countries; Ethiopia; Female; Goiter, Nodular; Humans; Iodine; Male; Methimazole; Middle Aged; Sodium Chloride, Dietary; Thyrotoxicosis; Young Adult
PubMed: 34182968
DOI: 10.1186/s12902-021-00796-5 -
Circulation Research May 2021Our insight into the diverse and complex nature of dilated cardiomyopathy (DCM) genetic architecture continues to evolve rapidly. The foundations of DCM genetics rest on... (Review)
Review
Our insight into the diverse and complex nature of dilated cardiomyopathy (DCM) genetic architecture continues to evolve rapidly. The foundations of DCM genetics rest on marked locus and allelic heterogeneity. While DCM exhibits a Mendelian, monogenic architecture in some families, preliminary data from our studies and others suggests that at least 20% to 30% of DCM may have an oligogenic basis, meaning that multiple rare variants from different, unlinked loci, determine the DCM phenotype. It is also likely that low-frequency and common genetic variation contribute to DCM complexity, but neither has been examined within a rare variant context. Other types of genetic variation are also likely relevant for DCM, along with gene-by-environment interaction, now established for alcohol- and chemotherapy-related DCM. Collectively, this suggests that the genetic architecture of DCM is broader in scope and more complex than previously understood. All of this elevates the impact of DCM genetics research, as greater insight into the causes of DCM can lead to interventions to mitigate or even prevent it and thus avoid the morbid and mortal scourge of human heart failure.
Topics: Alleles; Cardiomyopathy, Dilated; Cohort Studies; Connectin; Cross-Sectional Studies; Gene-Environment Interaction; Genetic Loci; Genetic Variation; Humans; Models, Statistical; Phenotype; Sarcomeres
PubMed: 33983834
DOI: 10.1161/CIRCRESAHA.121.318157 -
JACC. Cardiovascular Imaging Apr 2022The aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM).
OBJECTIVES
The aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM).
BACKGROUND
Patients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated.
METHODS
A total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test.
RESULTS
During a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P < 0.001). The maximum native T1 (HR: 1.04; 95% CI: 1.02-1.09) and maximum ECV fraction (HR: 1.14; 95% CI: 1.08-1.21) had associations with the primary endpoints in the patients with positive LGE (both P < 0.001), whereas the mean native T1 (HR: 1.13; 95% CI: 1.10-1.36) and mean ECV fraction (HR: 1.32; 95% CI: 1.12-1.53) had the best associations in the patients with negative LGE (all P < 0.001).
CONCLUSIONS
T1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.
Topics: Cardiomyopathy, Dilated; Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging, Cine; Male; Myocardium; Predictive Value of Tests; Prognosis; Stroke Volume
PubMed: 34538631
DOI: 10.1016/j.jcmg.2021.07.023 -
Korean Journal of Radiology Dec 2023Dilated cardiomyopathy (DCM) is one of the most common types of non-ischemic cardiomyopathy. DCM is characterized by left ventricle (LV) dilatation and systolic... (Review)
Review
Dilated cardiomyopathy (DCM) is one of the most common types of non-ischemic cardiomyopathy. DCM is characterized by left ventricle (LV) dilatation and systolic dysfunction without coronary artery disease or abnormal loading conditions. DCM is not a single disease entity and has a complex historical background of revisions and updates to its definition because of its diverse etiology and clinical manifestations. In cases of LV dilatation and dysfunction, conditions with phenotypic overlap should be excluded before establishing a DCM diagnosis. The differential diagnoses of DCM include ischemic cardiomyopathy, valvular heart disease, burned-out hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and non-compaction. Cardiac magnetic resonance (CMR) imaging is helpful for evaluating DCM because it provides precise measurements of cardiac size, function, mass, and tissue characterization. Comprehensive analyses using various sequences, including cine imaging, late gadolinium enhancement imaging, and T1 and T2 mapping, may help establish differential diagnoses, etiological work-up, disease stratification, prognostic determination, and follow-up procedures in patients with DCM phenotypes. This article aimed to review the utilities and limitations of CMR in the diagnosis and assessment of DCM.
Topics: Humans; Cardiomyopathy, Dilated; Contrast Media; Magnetic Resonance Imaging, Cine; Gadolinium; Magnetic Resonance Imaging; Myocardial Ischemia; Predictive Value of Tests; Ventricular Function, Left
PubMed: 38016680
DOI: 10.3348/kjr.2023.0531 -
Journal of the American College of... May 2023Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for...
BACKGROUND
Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD).
OBJECTIVES
This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients.
METHODS
Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results.
RESULTS
A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM.
CONCLUSIONS
Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.
Topics: Female; Humans; Male; Black People; Cardiomyopathy, Dilated; Echocardiography; Ethnicity; Hispanic or Latino; Hypertrophy, Left Ventricular; Adult; Middle Aged
PubMed: 37225358
DOI: 10.1016/j.jacc.2023.03.419