scholarly journals Integrin β1D Deficiency–Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 141 (18) ◽  
pp. 1477-1493 ◽  
Author(s):  
Yihui Wang ◽  
Chunyan Li ◽  
Ling Shi ◽  
Xiuyu Chen ◽  
Chen Cui ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Polymorphic Ventricular Tachycardia ◽  
Ventricular Cardiomyopathy ◽  
Open Probability ◽  
Increased Risk

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias, and increased risk of sudden cardiac death. The guideline for management of ARVC in patients is to improve quality of life by reducing arrhythmic symptoms and to prevent sudden cardiac death. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood. Methods: Using protein mass spectrometry analyses, we identified that integrin β1 is downregulated in ARVC hearts without changes to Ca 2+ -handling proteins. As adult cardiomyocytes express only the β1D isoform, we generated a cardiac specific β1D knockout mouse model and performed functional imaging and biochemical analyses to determine the consequences of integrin β1D loss on function in the heart in vivo and in vitro. Results: Integrin β1D deficiency and RyR2 Ser-2030 hyperphosphorylation were detected by Western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found that purified integrin β1D protein could stabilize RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time. Also, β1D knockout mice exhibited normal cardiac function and morphology but presented with catecholamine-sensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca 2+ handling in β1D knockout cardiomyocytes. Mechanistically, we revealed that loss of DSP (desmoplakin) induces integrin β1D deficiency in ARVC mediated through an ERK1/2 (extracellular signal–regulated kinase 1 and 2)–fibronectin–ubiquitin/lysosome pathway. Conclusions: Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.

scholarly journals Efficacy of epicardial and endocardial ablation in the prevention of ventricular tachycardia in arrythmogenic right ventricular cardiomyopathy- a meta analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Sattar ◽  
W Ullah ◽  
S Mamtani ◽  
C Alraies
Keyword(s):  
Ventricular Tachycardia ◽  
Catheter Ablation ◽  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Polymorphic Ventricular Tachycardia ◽  
Secondary Outcome ◽  
Ventricular Cardiomyopathy ◽  
Mapping Techniques ◽  
Post Hoc

Abstract Introduction Ventricular tachycardia is a major complication associated with increased risk of sudden cardiac death in arrhythmogenic ventricular cardiomyopathy. Recurrence of VT status post catheter endocardial ablation with conventional mapping is a evolving discussion in management of VT prevention in ARVC. With the evolution of new mapping techniques to locate ectopic foci of VT, a combination of endo- and epicardial catheter ablation have proven to be efficacious in the prevention of frequency of VT recurrence and its duration. Methods Using PubMed, Ovid (MEDLINE) and Cochrane database we searched using the MeSH terms including: “arrhythmogenic right ventricular cardiomyopathy”, “arrhythmogenic right ventricular dysplasia”, “monomorphic ventricular tachycardia”, “polymorphic ventricular Tachycardia”, “endocardial catheter ablation”, “epicardial catheter ablation”. The primary outcomes were to assess VT frequency and duration status post endocardial or epicardial or a combination of both types of ablation. The secondary outcome includes sudden cardiac arrest or sudden cardiac death after procedure. ANOVA with post HOC analysis was performed using SPSS v.26 (IBM Corp, NY, USA) Results A total of 33 studies included 1437 patients with a mean male=67%. The data analysis showed a mean VT prevention for endocardial ablation was 65%, epicardial 78%, and for combined epi-endocardial was 89% (figure-1). The mean procedural mortality rate was 2%. In order to test the hypothesis that combined epi-endocardial ablation was more successful in the prevention of VT recurrence, we performed a one-way analysis of variance (ANOVA). The analysis was statistically significant F(2,14)=5.879, 95% CI, p=0.014. Post Hoc test (Tukey HSD test) with multiple comparisons indicated that patients who underwent combined epi-endocardial ablation experienced a statistically significant difference in VT prevention of 89% (95% CI p=0.01) compared to only endocardial ablation, mean VT prevention of 65% (95% CI, p=0.189) or only epicardial, mean VT prevention of 78% (95% CI, p=0.353). Conclusion With new mapping techniques, use of endocardial, and epicardial ablation is linked to decrease VT frequency, duration, ICD shocks, and sudden cardiac death in patients with ARVC in cohorts with prior failure of antiarrhythmics. Total VT Prevention across target sites Funding Acknowledgement Type of funding source: None

Risk stratification for sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy

ESC CardioMed ◽  
2018 ◽  
pp. 2320-2322
Author(s):  
Firat Duru ◽  
Corinna Brunckhorst
Keyword(s):  
Risk Factors ◽  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Left Ventricle ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Sustained Ventricular Tachycardia ◽  
Ventricular Cardiomyopathy ◽  
The Right

Arrhythmogenic right ventricular cardiomyopathy is an inherited disease characterized by fibrofatty infiltration of the myocardium. Patients suffer from palpitations, presyncope, or syncope, which typically present during or after physical exercise. However, in a minority of cases, sudden cardiac death (SCD) may be the first disease manifestation. SCD in patients with arrhythmogenic right ventricular cardiomyopathy is difficult to predict and there are often no alarming signs or symptoms. Patients with a history of an aborted SCD due to ventricular fibrillation and those who have sustained ventricular tachycardia, or severe dysfunction of the right or left ventricle, or both, are considered to be at high risk for future arrhythmic events. The occurrence of unexplained syncope, non-sustained ventricular tachycardia, and moderate dysfunction of the right or left ventricle, or both, puts the patient at an intermediate risk. Other independent risk factors for adverse events include inducibility at programmed ventricular stimulation, young age at the time of diagnosis, male sex, and compound/digenic heterozygosity of desmosomal gene mutations. Electrocardiographic risk factors for adverse arrhythmic events include T-wave inversion across precordial and inferior leads, low QRS amplitude, and QRS fragmentation. Healthy gene carriers are considered to be at low risk for future arrhythmic events.

scholarly journals Late Presentation of Arrhythmogenic Right Ventricular Cardiomyopathy : Role of Non Invasive Modalities for The Diagnosis

2019 ◽  
Vol 6 (2) ◽  
pp. 131-136
Author(s):  
Safir Sungkar ◽  
Mochamad Arif Nugroho
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
The Elderly ◽  
Late Presentation ◽  
Ventricular Cardiomyopathy ◽  
Non Invasive

Background : Arrhythmogenic right ventricular cardiomyopathy(ARVC) is an inherited myocardial disease affecting predominantly young people and manifests as sustained ventricular tachycardia, sudden cardiac death (SCD) or heart failure. However, its first manifestation in older patients is infrequent. Diagnosis of ARVC remains a clinical challenge and need further investigation. Our case report investigated role of non invasive modalities for diagnosis of ARVC patient. Case Presentation : A 65 year old man was admitted to the hospital with symptoms of palpitationand near syncope. An Electrocardiogram (ECG) showed a sustained VT with LBBB morphology and inferior axis. The patient was cardioverted to sinus rhytm with a single 100J shock. Postcardioversion ECG showed an epsilon wave in right precordial leads. Echocardiography revealed extensive RV enlargement and reduce function. Our patient had three major (RV aneurysm, epsilon wave and T wave inversion) and one minor criteria (sustained LBBB type-VT with inferior axis)making the diagnosis of ARVC definite according to the revised Task Forced Criteria. Conclusion: ARVC may have a very late presentation and this diagnosis should be considered as a potential cause of sustained VT of RV origin among the elderly. ECG and echocardiography as non invasive modalities have an important role for the diagnosis of patients with suspected ARVC. Keywords :Arrhythmogenic right ventricular cardiomyopathy,ventricular tachycardia, sudden cardiac death, diagnosis.

scholarly journals Arrhythmogenic right ventricular cardiomyopathy or athlete's heart? Challenges in assessment of right heart morphology and function

2019 ◽  
Vol 89 (1) ◽  
Author(s):  
Francesco Antonini-Canterin ◽  
Concetta Di Nora
Keyword(s):  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
Young Athletes ◽  
Right Heart ◽  
Lack Of Information ◽  
And Function ◽  
Athlete's Heart

The incidence of sudden cardiac death (SCD) in young athletes varies among studies, due to the disagreement in the definitions and the lack of information in this field.

scholarly journals Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs

Circulation ◽  
2004 ◽  
Vol 109 (9) ◽  
pp. 1180-1185 ◽  
Author(s):  
Cristina Basso ◽  
Philip R. Fox ◽  
Kathryn M. Meurs ◽  
Jeffrey A. Towbin ◽  
Alan W. Spier ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
Boxer Dogs

scholarly journals Possibility of the Subcutaneous Implantable Cardioverter-Defibrillator for Prevention of Sudden Cardiac Death in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

2021 ◽  
Author(s):  
Shingo Sasaki
Keyword(s):  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Implantable Cardioverter Defibrillator ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Young Patients ◽  
Ventricular Myocardium ◽  
Hereditary Disease ◽  
Ventricular Cardiomyopathy ◽  
Cardioverter Defibrillator

The EMBLEM™ entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) system (Boston Scientific, Marlborough, Massachusetts, USA) was introduced as a new alternative to the conventional transvenous implantable cardioverter-defibrillator and has been expected to reduce device-related complications, especially in young patients who require long-term lead placement. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a well-known hereditary disease recognized as a cause of sudden cardiac death (SCD) in young adults. However, the precise clinical role of S-ICD in patients with ARVC remains to be defined because of the low QRS amplitude of subcutaneous electrocardiogram (S-ECG) followed by the high incidence of inappropriate shock (IAS) delivery due to oversensing. It is well known that the sensing of S-ICD is largely dependent on the QRS/T ratio of S-ECG. The decrease in the QRS amplitude is more likely to lead to oversensing such as T wave or myopotential oversensing. In patients with ARVC, the decrease in the QRS amplitude due to degeneration of the right ventricular myocardium progresses overtime. In this chapter, we would like to discuss the usefulness of S-ICD lead repositioning for young adult patients with ARVC based on our experience of patients with IAS.

scholarly journals Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): A Multinational Collaboration

2020 ◽  
Author(s):  
Julia Cadrin-Tourigny ◽  
Laurens P. Bosman ◽  
Weijia Wang ◽  
Rafik Tadros ◽  
Aditya Bhonsale ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Cox Regression ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Right Ventricular Ejection Fraction ◽  
Ventricular Cardiomyopathy ◽  
Clinical Predictors ◽  
Ventricular Ejection Fraction

Background - Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in ARVC patients. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods - We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 pre-specified clinical predictors with LTVA (SCD, aborted SCD, sustained or ICD treated VT>250 bpm) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable or ICD treated VT; or aborted SCD), syncope, 24-hour premature ventricular complexes (PVC) count, the number of anterior and inferior leads with T-wave inversion (TWI), left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results - A total of 864 definite ARVC patients (40±16 years; 53% male) were included. Over 5.75 years [IQR 2.77, 10.58] of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 pre-specified clinical predictors, only 4 (younger age, male sex, PVC count and number of leads with TWI) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (p=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI:0.69-0.80) and calibration slope of 0.95 (95% CI:0.94-0.98) indicating minimal over-optimism. Conclusions - LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.

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