Episodic Myocarditis in Arrhythmogenic Cardiomyopathy

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.

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Sustained ventricular tachycardia of left, right or both bundle branch block morphology in patients with Arrhythmogenic Cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.0452 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Milman ◽

M Laredo ◽

R Roudijk ◽

G Peretto ◽

A Andorin ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Right Bundle Branch Block ◽

Left Bundle Branch Block ◽

Clinical Course ◽

Left Ventricular ◽

Funding Source ◽

Arrhythmogenic Cardiomyopathy ◽

Icd Implantation ◽

Bundle Branch Block ◽

Group 3

Abstract Aims In arrhythmogenic cardiomyopathy (ACM) sustained monomorphic ventricular tachycardia (VT) typically displays left bundle branch block (LBBB) morphology. Sustained VT with right bundle branch block (RBBB) morphology is very rare despite the frequent left ventricular involvement. The present study sought to assess the prevalence of spontaneous sustained LBBB-VT, RBBB-VT or both as well as clinical and genetic differences associated with these VT types. Methods and results Twenty-six centers from 11 European countries provided information on 952 patients with ACM and >1 episode of sustained VT observed during the patients' clinical course. VT was classified as: LBBB-VT; RBBB-VT or LBBB+RBBB-VT. Among 952 patients, 881 (92.5%) had LBBB-VT alone, 71 (7.5%) had RBBB-VT [alone in 42 (4.4%) patients or with LBBB-VT in 29 (3.0%) patients]. Male prevalence was 90.5%, 79.2% and 55.9% in the RBBB-VT, LBBB-VT and LBBB+RBBB-VT groups, respectively (P=0.001). Patients' age at first VT did not differ amongst the 3 VT groups. ICD implantation was more frequent for the RBBB-VT and the LBBB+RBBB groups (≈90% each) vs. 67.9% for the LBBB-VT group (P=0.001). Death incidence (9.5%–17.2%) was not significantly different between the 3 groups (P=0.425). Plakophylin-2 mutations predominated in the LBBB-VT and LBBB-VT+RBBB-VT groups (47.2% and 27.3%, respectively) and Desmoplakin mutations in the RBBB-VT group (36.7%). Conclusion This large European survey demonstrates: 1) Sustained RBBB-VT is documented in 7.5% patients with ACM; 2) Males markedly predominate in the RBBB-VT and LBBB-VT groups but not in the LBBB+RBBB VT group; 3) Distribution of desmosomal mutations appears to be different in the 3 VT groups. Funding Acknowledgement Type of funding source: None

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Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

International Journal of Molecular Sciences ◽

10.3390/ijms22073786 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3786

Author(s):

Andreas Brodehl ◽

Alexey Meshkov ◽

Roman Myasnikov ◽

Anna Kiseleva ◽

Olga Kulikova ◽

...

Keyword(s):

Medical History ◽

Splice Site Mutation ◽

Pathogenic Mutation ◽

Large Deletion ◽

Loss Of Function ◽

Arrhythmogenic Cardiomyopathy ◽

Site Mutation ◽

Snp Arrays ◽

Number Of Patients ◽

History Of

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.

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Mid‐ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm: An important subtype of arrhythmogenic cardiomyopathy

Annals of Noninvasive Electrocardiology ◽

10.1111/anec.12638 ◽

2019 ◽

Vol 24 (5) ◽

Cited By ~ 1

Author(s):

Li Cui ◽

Gary Tse ◽

Zhiqiang Zhao ◽

George Bazoukis ◽

Konstantinos P. Letsas ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Arrhythmogenic Cardiomyopathy ◽

Obstructive Hypertrophic Cardiomyopathy ◽

Apical Aneurysm

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Quantitative Approach to Fragmented QRS in Arrhythmogenic Cardiomyopathy: From Disease towards Asymptomatic Carriers of Pathogenic Variants

Journal of Clinical Medicine ◽

10.3390/jcm9020545 ◽

2020 ◽

Vol 9 (2) ◽

pp. 545 ◽

Cited By ~ 3

Author(s):

Rob W. Roudijk ◽

Laurens P. Bosman ◽

Jeroen F. van der Heijden ◽

Jacques M. T. de Bakker ◽

Richard N. W. Hauer ◽

...

Keyword(s):

Early Stage ◽

Pathogenic Variant ◽

Observer Agreement ◽

Arrhythmogenic Cardiomyopathy ◽

Fragmented Qrs ◽

Early Disease Detection ◽

Pathogenic Variants ◽

Disease Penetrance ◽

Ecg Leads ◽

And Control

Fragmented QRS complexes (fQRS) are common in patients with arrhythmogenic cardiomyopathy (ACM). A new method of fQRS quantification may aid early disease detection in pathogenic variant carriers and assessment of prognosis in patients with early stage ACM. Patients with definite ACM (n = 221, 66%), carriers of a pathogenic ACM-associated variant without a definite ACM diagnosis (n = 57, 17%) and control subjects (n = 58, 17%) were included. Quantitative fQRS (Q-fQRS) was defined as the total amount of deflections in the QRS complex in all 12 electrocardiography (ECG) leads. Q-fQRS was scored by a single observer and reproducibility was determined by three independent observers. Q-fQRS count was feasible with acceptable intra- and inter-observer agreement. Q-fQRS count is significantly higher in patients with definite ACM (54 ± 15) and pathogenic variant carriers (55 ± 10) compared to controls (35 ± 5) (p < 0.001). In patients with ACM, Q-fQRS was not associated with sustained ventricular arrhythmia (p = 0.701) at baseline or during follow-up (p = 0.335). Both definite ACM patients and pathogenic variant carriers not fulfilling ACM diagnosis have a higher Q-fQRS than controls. This may indicate that increased Q-fQRS is an early sign of disease penetrance. In concealed and early stages of ACM the role of Q-fQRS for risk stratification is limited.

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