OBJECTIVE: To explore the clinical and genetic characteristics of a child with Arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: A 6-year-old boy with ARVC who had visited Fujian Provincial Children's Hospital on August 23, 2022 was selected as the study subject. Relevant clinical data were collected, and peripheral venous blood samples were collected from the child and his parents for genetic testing through whole exome sequencing (WES). Sanger sequencing was carried out for family verification, and pathogenicity analysis was conducted for the candidate variants. RESULTS: The child had exhibited clinical symptoms including systemic edema, generalized heart enlargement, universal reduction of interventricular septum and ventricular wall movement, reduced left ventricular diastolic and systolic function, and reduced right ventricular systolic function. WES revealed that the child has harbored compound heterozygous variants of the PKP2 gene, namely c.119_122del (p.Leu40ArgfsTer71) and c.1978G>A (p.Gly660Arg), which were verified by Sanger sequencing to be respectively inherited from his father and mother. The c.119_122del variant has not been recorded in the 1000 Genomes, gnomAD and ExAC databases, and was predicted to lead to truncation of the PKP2 protein by SWISS-MODEL and PyMOL online software and classified as likely pathogenic based on the guidelines jointly developed by the American College of Medical Genetics and Genomics (ACMG) and ClinGen. The c.1978G>A variant has also not been recorded in the 1000 Genomes, gnomAD and ExAC databases, and was predicted to be deleterious by online software including REVEL, SIFT, CADD, Mutation Taster, and PolyPhen-2. The amino acid encoded by the variant site was highly conserved among various species by analysis using T-coffee and ESPript v3.0 online servers. The variant may affect the protein function by SWISS-MODEL and PyMOL online server analysis, and was classified as likely pathogenic based on the guidelines jointly developed by the ACMG and ClinGen. CONCLUSION The compound heterozygous variants of c.119_122del (p.Leu40ArgfsTer71) and c.1978G>A (p.Gly660Arg) of the PKP2 gene probably underlay the ARVC in this child. Above finding has broadened the spectrum of PKP2 gene variants and provided a reference for the diagnosis and genetic counseling.
Male ; Child ; Humans ; Arrhythmogenic Right Ventricular Dysplasia/genetics* ; Diastole ; Ethnicity ; Genetic Counseling ; Genetic Testing ; Plakophilins/genetics*

Arrhythmogenic Right Ventricular Dysplasia/genetics* ; Genotype ; Humans ; Phenotype ; Risk Assessment

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of inherited cardio-myopathy, which is characterized by fibro-fatty replacement of right ventricular myocardium, leading to ventricular arrhythmia. However, rapid atrial arrhythmias are also common, including atrial fibrillation, atrial flutter and atrial tachycardia. Long term rapid atrial arrhythmia can lead to further deterioration of cardiac function. This case is a 51-year-old male. He was admitted to Department of Cardiology, Peking University Third Hospital with palpitation and fatigue after exercise. Electrocardiogram showed incessant atrial tachycardia. Echocardiography revealed dilation of all his four chambers, especially the right ventricle, with the left ventricular ejection fraction of 40% and the right ventricular hypokinesis. Cardiac magnetic resonance imaging found that the right ventricle was significantly enlarged, and the right ventricular aneurysm had formed; the right ventricular ejection fraction was as low as 8%, and the left ventricular ejection fraction was 35%. The patients met the diagnostic criteria of ARVC, and both left and right ventricles were involved. His physical activities were restricted, and metoprolol, digoxin, spironolactone and ramipril were given. Rivaroxaban was also given because atrial tachycardia could cause left atrial thrombosis and embolism. His atrial tachycardia converted spontaneously to normal sinus rhythm after these treatments. Since the patient had severe right ventricular dysfunction, frequent premature ventricular beats and non-sustained ventricular tachycardia on Holter monitoring, indicating a high risk of sudden death, implantable cardioverter defibrillator (ICD) was implanted. After discharge from hospital, physical activity restriction and the above medicines were continued. As rapid atrial arrhythmia could lead to inappropriate ICD shocks, amiodarone was added to prevent the recurrence of atrial tachycardia, and also control ventricular arrhythmia. After 6 months, echocardiography was repeated and showed that the left ventricle diameter was reduced significantly, and the left ventricular ejection fraction increased to 60%, while the size of right ventricle and right atrium decreased slightly. According to the clinical manifestations and outcomes, he was diagnosed with ARVC associated with arrhythmia induced cardiomyopathy. According to the results of his cardiac magnetic resonance imaging, the patient had left ventricular involvement caused by ARVC, and the persistent atrial tachycardia led to left ventricular systolic dysfunction.
Arrhythmogenic Right Ventricular Dysplasia/complications* ; Atrial Fibrillation ; Humans ; Male ; Middle Aged ; Stroke Volume ; Ventricular Function, Left ; Ventricular Function, Right

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.
Arrhythmogenic Right Ventricular Dysplasia ; Cardiomyopathies/genetics* ; Desmoplakins/genetics* ; Hair Diseases ; Humans ; Keratoderma, Palmoplantar

OBJECTIVE: To explore the correlation between DSG2, TTN and GATA4 genes and Brugada syndrome in Henan Province of China. METHODS: From February 2017 to February 2019, 100 patients with Brugada syndrome and 100 healthy individuals were selected as the study and the control groups, respectively. Electrocardiogram and echocardiography were carried out, and peripheral blood samples was collected. Coding regions of DSG2, TTN and GATA4 genes were amplified by PCR and sequenced. The results were compared with standard sequences from GenBank. RESULTS: Electrocardiogram showed that all patients from the study group had ventricular arrhythmia, 87 cases (87%) presented ventricular tachycardia (VT), 84 cases (84%) presented T wave inversion, and 51 cases (51%) presented Epsilon wave. Echocardiography showed that the right ventricle in the study group was enlarged with the inner diameter of the right ventricle being (40.0±13.3) mm, and the right ventricle showed various degree of abnormal systolic function. The enlargement of right atrium accounted for 64%, and the involvement of the left ventricle accounted for 27%. The right ventricular diameter and left ventricular diastolic diameter of the study group were significantly greater than those of the control group (P< 0.05). DNA sequencing showed that 60 patients carried DSG2 gene variants, among which 18 had missense variant of exon 8. Fifty patients carried TTN gene variants, including 8 in the A-band domain and 3 in the I-band domain. Twenty patients carried 3 variants of the GATA4 gene. CONCLUSION Variants of the DSG2, TTN and GATA4 genes in Henan region are correlated with the onset of Brugada syndrome.
Arrhythmogenic Right Ventricular Dysplasia ; Brugada Syndrome/genetics* ; China ; Connectin ; Desmoglein 2/genetics* ; GATA4 Transcription Factor ; Humans ; Pedigree ; Sequence Analysis, DNA

Objective To explore the association of cardiac disease associated genetic variants and the high incidence of Yunnan sudden unexplained death （YNSUD） in Yi nationality. Methods The genomic DNA was extracted from peripheral blood samples collected from 205 Yi villagers from YNSUD aggregative villages （inpatient group） and 197 healthy Yi villagers from neighboring villages （control group）. Fifty-two single nucleotide variants （SNVs） of 25 cardiac disease associated genes were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. The SPSS 17.0 was used to analyze data. The pathogenicities of variants with differences between the two groups that have statistical significance were predicted by protein function prediction software PolyPhen-2 and SIFT. All villagers from inpatient group were given electrocardiogram （ECG） examination using a 12-lead electrocardiograph. Results The allele frequency and the genotype frequency of missense mutation DSG2 （rs2278792, c.2318G>A, p.R773K） of pathogenic genes of arrhythmogenic right ventricular cardiomyopathy （ARVC） in inpatient group was higher than that in control group （P<0.05）. Abnormal ECG changes were detected in 71 individuals （34.6%） in the inpatient group, among which 54 individuals carried R773K mutation, including clockwise （counterclockwise） rotation, left （right） axis deviation, ST segment and T wave alteration and heart-blocking. Conclusion Definite pathogenic mutations have not been found in the 52 cardiac disease genes associated SNVs detected in Yi nationality in regions with high incidence of YNSUD. The cause of high incidence of YNSUD in Yi nationality needs further study.
Arrhythmogenic Right Ventricular Dysplasia ; China/epidemiology* ; Death, Sudden/etiology* ; Death, Sudden, Cardiac/etiology* ; Ethnicity/genetics* ; Humans ; Incidence ; Mutation

Sarcoidosis is a multisystem disease characterized by noncaseating granulomas. Cardiac involvement is known to have poor prognosis because it can manifest as a serious condition such as the conduction abnormality, heart failure, ventricular arrhythmia, or sudden cardiac death. Although early diagnosis and early treatment is critical to improve patient prognosis, the diagnosis of CS is challenging in most cases. Diagnosis usually relies on endomyocardial biopsy (EMB), but its diagnostic yield is low due to the incidence of patchy myocardial involvement. Guidelines for the diagnosis of CS recommend a combination of clinical, electrocardiographic, and imaging findings from various modalities, if EMB cannot confirm the diagnosis. Especially, the role of advanced imaging such as cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET), has shown to be important not only for the diagnosis, but also for monitoring treatment response and prognostication. CMR can evaluate cardiac function and fibrotic scar with good specificity. Late gadolinium enhancement (LGE) in CMR shows a distinctive enhancement pattern for each disease, which may be useful for differential diagnosis of CS from other similar diseases. Effectively, T1 or T2 mapping techniques can be also used for early recognition of CS. In the meantime, PET can detect and quantify metabolic activity and can be used to monitor treatment response. Recently, the use of a hybrid CMR-PET has introduced to allow identify patients with active CS with excellent co-localization and better diagnostic accuracy than CMR or PET alone. However, CS may show various findings with a wide spectrum, therefore, radiologists should consider the possible differential diagnosis of CS including myocarditis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy, amyloidosis, and arrhythmogenic right ventricular cardiomyopathy. Radiologists should recognize the differences in various diseases that show the characteristics of mimicking CS, and try to get an accurate diagnosis of CS.
Amyloidosis ; Arrhythmias, Cardiac ; Arrhythmogenic Right Ventricular Dysplasia ; Biopsy ; Cardiomyopathy, Dilated ; Cardiomyopathy, Hypertrophic ; Cicatrix ; Death, Sudden, Cardiac ; Diagnosis ; Diagnosis, Differential ; Early Diagnosis ; Electrocardiography ; Electrons ; Gadolinium ; Granuloma ; Heart Defects, Congenital ; Humans ; Incidence ; Magnetic Resonance Imaging ; Myocarditis ; Positron-Emission Tomography ; Prognosis ; Sarcoidosis ; Sensitivity and Specificity

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is predominantly an inherited cardiomyopathy with typical histopathological characteristics of fibro-fatty infiltration mainly involving the right ventricular (RV) inflow tract, RV outflow tract, and RV apex in the majority of patients. The above pathologic evolution frequently brings patients with ARVD/C to medical attention owing to the manifestation of syncope, sudden cardiac death (SCD), ventricular arrhythmogenesis, or heart failure. To prevent future or recurrent SCD, an implantable cardiac defibrillator (ICD) is highly desirable in patients with ARVD/C who had experienced unexplained syncope, hemodynamically intolerable ventricular tachycardia (VT), ventricular fibrillation, and/or aborted SCD. Notably, the management of frequent ventricular tachyarrhythmias in ARVD/C is challenging, and the use of antiarrhythmic drugs could be unsatisfactory or limited by the unfavorable side effects. Therefore, radiofrequency catheter ablation (RFCA) has been implemented to treat the drug-refractory VT in ARVD/C for decades. However, the initial understanding of the link between fibro-fatty pathogenesis and ventricular arrhythmogenesis in ARVD/C is scarce, the efficacy and prognosis of endocardial RFCA alone were limited and disappointing. The electrophysiologists had broken through this frontier after better illustration of epicardial substrates and broadly application of epicardial approaches in ARVD/C. In recent works of literature, the application of epicardial ablation also successfully results in higher procedural success and decreases VT recurrences in patients with ARVD/C who are refractory to the endocardial approach during long-term follow-up. In this article, we review the important evolution on the delineation of arrhythmogenic substrates, ablation strategies, and ablation outcome of VT in patients with ARVD/C.
Anti-Arrhythmia Agents ; Arrhythmogenic Right Ventricular Dysplasia ; Cardiomyopathies ; Catheter Ablation ; Catheters ; Death, Sudden, Cardiac ; Defibrillators ; Epicardial Mapping ; Follow-Up Studies ; Heart Failure ; Humans ; Prognosis ; Recurrence ; Syncope ; Tachycardia ; Tachycardia, Ventricular ; Ventricular Fibrillation

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy characterized by predominant right ventricular fibro-fatty replacement, right ventricular dysfunction and ventricular arrhythmias. It is a rare but important cause of sudden cardiac death in children and young adults. A meta-analysis on risk stratification of major ventricular tachyarrhythmic events indicating the need for implantable cardioverter defibrillator therapy in ARVC was performed. METHODS: The pubmed database was searched from its inception to May 2015. Of the 433 citations identified, 12 were included in this meta-analysis. Data regarding major ventricular tachyarrhythmic events were retrieved in 817 subjects from the studies. For the variables, a combined odds ratio (OR) was calculated using a fixed-effects meta-analysis. RESULTS: Extensive right ventricular dysfunction (OR, 2.44), ventricular late potential (OR, 1.66), inducible ventricular tachyarrhythmia during electrophysiology study (OR, 3.67), non-sustained ventricular tachycardia (OR, 3.78), and history of fatal event/sustained VT (OR, 5.66) identified as significant risk factors (p < 0.0001). CONCLUSION: This meta-analysis shows that extensive right ventricular dysfunction, ventricular late potential, inducible ventricular tachyarrhythmia during electrophysiological study, non-sustained ventricular tachycardia, and history of sustained ventricular tachycardia/fibrillation are consistently reported risk factors of major ventricular tachyarrhythmic events indicating implantable cardioverter defibrillator therapy in patients with ARVC.
Arrhythmias, Cardiac ; Arrhythmogenic Right Ventricular Dysplasia* ; Cardiomyopathies ; Child ; Death, Sudden ; Death, Sudden, Cardiac ; Defibrillators ; Electrophysiology ; Humans ; Odds Ratio ; Risk Factors ; Tachycardia ; Tachycardia, Ventricular ; Ventricular Dysfunction, Right ; Young Adult

Differentiating arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) from other cardiomyopathies is clinically important but challenging. Although the modified Task Force Criteria can facilitate diagnosis of ARVD/C according to clinical manifestations, histopathological examination plays a pivotal role in excluding other diseases that can mimic ARVD/C. Here, we report a patient with amyloidosis that initially presented similarly to ARVD/C. The diagnosis was confirmed by endomyocardial biopsy, and catheter ablation eliminated the ventricular tachyarrhythmias through an epicardial approach.
Advisory Committees ; Amyloidosis* ; Arrhythmogenic Right Ventricular Dysplasia ; Biopsy ; Cardiomyopathies ; Catheter Ablation* ; Catheters* ; Diagnosis ; Humans ; Tachycardia ; Tachycardia, Ventricular