Myocarditis-like Episodes in Patients with Arrhythmogenic Cardiomyopathy: A Systematic Review on the So-Called Hot-Phase of the Disease

Biomolecules, Год журнала: 2022, Номер 12(9), С. 1324 - 1324

Опубликована: Сен. 19, 2022

Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial disease, characterized by myocytes necrosis with fibrofatty substitution and ventricular arrhythmias that can even lead to sudden cardiac death. The presence of inflammatory cell infiltrates in endomyocardial biopsies or autoptic specimens ACM patients has been reported, suggesting possible role inflammation the pathophysiology disease. Furthermore, chest pain episodes accompanied electrocardiographic changes troponin release have observed defined as “hot-phase” phenomenon. aim this critical systematic review was assess clinical features presenting episodes. According PRISMA guidelines, search run PubMed, Scopus Web Science electronic databases using following keywords: “arrhythmogenic cardiomyopathy”; “myocarditis” “troponin” “hot-phase”. A total 1433 titles were retrieved, which 65 studies potentially relevant topic. Through application inclusion exclusion criteria, 9 papers reporting 103 who had experienced hot-phase selected for review. Age at time available 76% cases, mean age reported being 26 years ± 14 (min 2–max 71 years). Overall, 86% showed left epicardial LGE. At episodes, 49% received diagnosis (Arrhythmogenic majority cases), 19% dilated 26% acute myocarditis. genetic study, Desmoplakin (DSP) more represented disease-gene (69%), followed Plakophillin-2 (9%) Desmoglein-2 (6%). In conclusion, showing are usually young, DSP most common disease gene, accounting 69% cases. Currently, progression arrhythmic risk stratification remains be clarified.

Язык: Английский

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Sudden Cardiac Death in Athletes: Facts and Fallacies

Journal of Cardiovascular Development and Disease, Год журнала: 2023, Номер 10(2), С. 68 - 68

Опубликована: Фев. 5, 2023

The benefits of exercise for cardiovascular and general health are many. However, sudden cardiac death (SCD) may occur in apparently healthy athletes who perform at the highest levels. A diverse spectrum diseases is implicated SCD athletes, while atherosclerotic coronary artery disease predominates individuals >35 years age, primary cardiomyopathies ion channelopathies prevalent young individuals. Prevention relies on implementation policies aimed early identification arrhythmogenic (such as screening) successful resuscitation widespread utilization automatic external defibrillators training members public cardiopulmonary resuscitation). This review will focus epidemiology aetiologies examine fallacies approach to this controversial field. Furthermore, potential strategies prevent these tragic events be discussed, analysing current practice, gaps knowledge future directions.

Язык: Английский

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Epigenetics in LMNA-Related Cardiomyopathy

Cells, Год журнала: 2023, Номер 12(5), С. 783 - 783

Опубликована: Март 1, 2023

Mutations in the gene for lamin A/C (LMNA) cause a diverse range of diseases known as laminopathies. LMNA-related cardiomyopathy is common inherited heart disease and highly penetrant with poor prognosis. In past years, numerous investigations using mouse models, stem cell technologies, patient samples have characterized phenotypic diversity caused by specific LMNA variants contributed to understanding molecular mechanisms underlying pathogenesis disease. As component nuclear envelope, regulates mechanostability function, chromatin organization, transcription. This review will focus on different cardiomyopathies mutations, address role organization regulation, discuss how these processes go awry

Язык: Английский

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DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from an Italian Cohort

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2490 - 2490

Опубликована: Янв. 27, 2023

Variants in desmoplakin gene (DSP MIM *125647) have been usually associated with Arrhythmogenic Cardiomyopathy (ACM), or Dilated (DCM) inherited an autosomal dominant manner. A cohort of 18 probands, characterized as heterozygotes for DSP variants by a target Next Generation Sequencing (NGS) cardiomyopathy panel, was analyzed. Cardiological, genetic data, and imaging features were retrospectively collected. total 16 heterozygous pathogenic likely identified, 75% (n = 12) truncating variants, n 2 missense 1 splicing variant, duplication variant. The mean age at diagnosis 40.61 years (IQR 31-47.25), 61% patients being asymptomatic 11, New York Heart Association (NYHA) class I) 39% mildly symptomatic 7, NYHA II). Notably, 7) presented clinical history presumed myocarditis episodes, chest pain, myocardial enzyme release, 12-lead electrocardiogram abnormalities normal coronary arteries, which recurrent 57% cases 4). About half the (55%, 10) varied degree left ventricular enlargement (LVE), four showing biventricular involvement. Eleven (61%) underwent implantable cardioverter defibrillator (ICD) implantation, 46.81 36.00-64.00). Cardiac magnetic resonance (CMRI) identified all delayed enhancement (DE) area consistent (LV) fibrosis, larger localization extent presenting episodes injury. These data confirm that DSP-related may represent distinct entity high arrhythmic burden, variable degrees LVE, Late Gadolinium Enhancement (LGE) subepicardial distribution myocarditis-like picture.

Язык: Английский

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A New Perspective on the Role of Alterations in Mitochondrial Proteins Involved in ATP Synthesis and Mobilization in Cardiomyopathies

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2768 - 2768

Опубликована: Март 19, 2025

The heart requires a continuous energy supply to sustain its unceasing contraction–relaxation cycle. Mitochondria, double-membrane organelle, generate approximately 90% of cellular as adenosine triphosphate (ATP) through oxidative phosphorylation, utilizing the electrochemical gradient established by respiratory chain. Mitochondrial function is compromised damage mitochondrial DNA, including point mutations, deletions, duplications, or inversions. Additionally, disruptions proteins associated with membranes regulating metabolic homeostasis can impair chain’s efficiency. This results in diminished ATP production and increased generation reactive oxygen species. review provides an overview mutations affecting transporters involved synthesis, particularly those synthesis mobilization, it examines their role pathogenesis specific cardiomyopathies.

Язык: Английский

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Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2675 - 2675

Опубликована: Янв. 31, 2023

Phospholamban (PLN) is a major regulator of cardiac contractility, and human mutations in this gene give rise to inherited cardiomyopathies. The deletion Arginine 14 the most-prevalent cardiomyopathy-related mutation, it has been linked arrhythmogenesis early death. Studies PLN-humanized mutant mice indicated an increased propensity arrhythmias, but underlying cellular mechanisms associated with R14del-PLN dysfunction absence any apparent structural remodeling remain unclear. present study addressed specific role myofilaments setting long-term effects heart. Maximal force was depressed skinned cardiomyocytes from both left right ventricles, effect more pronounced ventricle mice. In addition, Ca2+ sensitivity ventricles However, depressive on contractile parameters could be reversed positive inotropic drug omecamtiv mecarbil, myosin activator. At 12 months age, corresponding mean symptomatic age patients, transients were significantly ventricular cardiomyocytes. Echocardiography did not reveal alterations function or remodeling, although histological electron microscopy analyses subtle hearts. These findings suggest that aberrant myocyte calcium cycling contractility long term. altered myofilament activity characteristic hearts mecarbil may beneficial treating cardiomyopathy.

Язык: Английский

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Arrhythmogenic Right Ventricular Cardiomyopathy: A Comprehensive Review

Journal of Cardiovascular Development and Disease, Год журнала: 2025, Номер 12(2), С. 71 - 71

Опубликована: Фев. 13, 2025

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by structural abnormalities, arrhythmias, and a spectrum of genetic clinical manifestations. Clinically, ARVC structurally distinguished dilation due to increased adiposity fibrosis in the walls, it manifests as cardiac arrhythmias ranging from non-sustained tachycardia sudden death. Its prevalence has been estimated range 1 every 1000 5000 people, with its large being attributed variability penetrance asymptomatic significant burden. It even suggested that underestimated, presence genotypic mutations does not always lead manifestations would facilitate diagnosis. Additionally, while set criteria have place since 1990s, newer understanding this condition advancements technology prompted multiple revisions diagnostic for ARVC. Novel discoveries gene variants predisposing patients led established screening techniques providing insight into counseling management. This review aims provide an overview genetics, pathophysiology, approach will also focus on presentation, criteria, electrophysiological findings, including electrocardiogram characteristics, imaging findings MRI, 2D, 3D echocardiogram. Current management options-including anti-arrhythmic medications, device indications, ablation techniques-and effectiveness treatment be reviewed.

Язык: Английский

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Illuminating Cardiac Remodeling: Insights From [ ¹⁸ F]‐Fluorodeoxyglucose Positron Emission Tomography Imaging in Plakoglobin‐Associated Arrhythmogenic Cardiomyopathy

Journal of the American Heart Association, Год журнала: 2025, Номер 14(5)

Опубликована: Март 3, 2025

Background Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease, which presents with arrhythmias and sudden cardiac death, along progressive remodeling myocardial inflammation. This study aims to elucidate the patterns of [ 18 F]‐fluorodeoxyglucose ([ F]‐FDG) uptake in mouse model plakoglobin‐associated disease better understand its diagnostic potential. Methods Results Plakoglobin ( Jup ) knockout mice developed that presented an ACM‐like phenotype at 6 weeks age. Flow cytometry experiments showed significant increase immune cells, for example, expansion proinflammatory tissue‐injury macrophages. In vivo positron emission tomography ex autoradiography increased F]‐FDG genotype positive hearts. A correlative analysis between positivity macrophage infiltration using CD68 CD206 staining did not show colocalization. was primarily observed within fibrotic scar, whereas predominantly identified CD206‐negative tissue areas. Instead, signal seemed originate from cardiomyocytes adjacent areas remodeling. Morphometric revealed hypertrophy these cardiomyocytes, may reflect metabolic as compensatory response. Conclusions our murine ‐related ACM, strong detected, colocalized regional hypertrophic rather than inflammatory cells. These findings indicate valuable tool identifying localizing hypermetabolic associated providing insights into mechanisms potential strategies.

Язык: Английский

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Epicardial Adipose Tissue in Arrhythmogenic Cardiomyopathy

Biology, Год журнала: 2025, Номер 14(3), С. 278 - 278

Опубликована: Март 8, 2025

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by fibrofatty replacement of the ventricular myocardium, with estimated prevalence 1:5000 people in general population. Sudden cardiac death first manifestation this 16–23% patients ACM. Fibrofatty infiltration can be identified noninvasive magnetic resonance. Studies epicardial fat deposits have suggested pathogenic roles fats mediating diseases and arrhythmias. Although myocardial has been well described ACM, changes not investigated. Our study shows that ACM a higher amount EAT compared to controls. Additionally, seems increase evolution disease.

Язык: Английский

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Arrhythmogenic Cardiomyopathy PKP2-Related: Clinical and Functional Characterization of a Pathogenic Variant Detected in Two Italian Families

Genes, Год журнала: 2025, Номер 16(4), С. 419 - 419

Опубликована: Март 31, 2025

Background/Objectives: PKP2 (MIM *602861) is the most commonly gene associated with Arrhythmogenic Cardiomyopathy (ACM), an inherited cardiac muscle disorder. The aim of this study was to characterize phenotypical effect a heterozygous pathogenic c.2443_2448delAACACCinsGAAA variant in (NM_004572), detected two Italian families. Methods: Next Generation Sequencing (NGS) analysis carried out on probands, testing multigenic targeted panel. Segregation through Sanger sequencing other three and six positive members, Family 1 2, respectively. Thus, eleven patients were identified overall. A deep clinical evaluation performed according age groups parameters (symptoms, electrocardiogram, imaging, devices). To investigate molecular expression level, total RNA isolated from peripheral blood mononuclear cells (PBMCs) quantitative RT-polymerase chain reaction performed. at protein level analyzed PBMCs by Western blot analysis. Results: transcriptional levels resulted be reduced 48% carrying compared WT (p = 0.00015). Importantly, confirmed carriers variant, confirming haploinsufficiency effect. Conclusions: onset ACM can Sudden Cardiac Death, hence, it recommended perform segregation test first-degree relatives carriers, even if they are asymptomatic, purpose promptly detecting those risk.

Язык: Английский

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