Polymorphic Ventricular Tachycardia/Ventricular Fibrillation and Sudden Cardiac Death in the Normal Heart

2016 ◽  
Vol 8 (3) ◽  
pp. 581-591 ◽  
Author(s):  
Ashok J. Shah ◽  
Meleze Hocini ◽  
Arnaud Denis ◽  
Nicolas Derval ◽  
Frederic Sacher ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Ventricular Fibrillation ◽  
Cardiac Death ◽  
Polymorphic Ventricular Tachycardia ◽  
Normal Heart

scholarly journals GENETIC REASONS OF SUDDEN CARDIAC DEATH

2017 ◽  
Vol 19 (2) ◽  
pp. 15-22
Author(s):  
S N Kolyubaeva
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Long Qt Syndrome ◽  
Brugada Syndrome ◽  
Cardiac Death ◽  
Polymorphic Ventricular Tachycardia ◽  
Normal Heart ◽  
Short Qt Syndrome ◽  
Long Qt ◽  
Qt Syndrome

The review presents the recent data on genetic reasons of sudden cardiac death. Mutations discuss in gens associated with sudden cardiac death. Channalopathies, such as Brugada syndrome, long QT syndrome, short QT syndrome and catecholaminergic polymorphic ventricular tachycardia are characterized by arrhythmias in normal heart resulting from genetic anomalies in ion channels

Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 62-74 ◽  
Author(s):  
E. Z. Golukhova ◽  
O. I. Gromova ◽  
R. A. Shomahov ◽  
N. I. Bulaeva ◽  
L. A. Bockeria
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Ventricular Fibrillation ◽  
Long Qt Syndrome ◽  
Cardiac Death ◽  
Heart Rhythm ◽  
The United States ◽  
Polymorphic Ventricular Tachycardia ◽  
Long Qt ◽  
Qt Syndrome

The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called sudden cardiac death (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias - sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator).

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 Study of genetic markers of cardiac arrhythmias in Kazakhstan

2014 ◽  
Vol 2 ◽  
Author(s):  
Makhabbat Bekbossynova ◽  
Ainur Akilzhanova ◽  
Zhannur Abilova ◽  
Ayan Abdrahmanov ◽  
Omirbek Nuralinov
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Cardiac Arrhythmias ◽  
Cardiac Death ◽  
Novel Mutation ◽  
Hot Spot ◽  
Receptor Gene ◽  
Polymorphic Ventricular Tachycardia ◽  
Life Threatening ◽  
Genetically Determined

Introduction: Cardiac arrhythmias are the most common cause of mortality and sudden cardiac death worldwide. In the past decade, genetic factors underlying arrhythmogenic diseases have been revealed and given novel insights in to the understanding and treatment of arrhythmias predisposing one to sudden cardiac death.Material and methods: We conducted a pilot genetic screening of two patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and 14 patients with ventricular tachycardia (VT) for genetic variants in the human ryanodine receptor gene 2 (hRYR2). The most relevant 45 hot-spot exons of hRYR2 were amplified by polymerase chain reaction (PCR) and directly sequenced.Results: One novel mutation in a CPVT patient (c.A13892T; p.D4631V) and a novel mutation in a VT patient (c.G5428C; p.V1810L) were identified. Both variants are located at phylogenetically conserved positions and predicted pathogenesis. Three known synonymous SNPs (rs3765097, rs2253273, and TMP ESp1 237664067) were detected in the study group. No further variants within the target regions were detected in the study group.Conclusion: The results of study can be applied to risk asssessment for life-threatening arrhythmias and assist in development of appropriate strategies for prevention of sudden cardiac death. The implementation of these strategies would assist in the management of patients with genetically determined arrhythmias in Kazakhstan.

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

scholarly journals Human RyR2 (Ryanodine Receptor 2) Loss-of-Function Mutations

2021 ◽  
Vol 14 (9) ◽  
Author(s):  
Yanhui Li ◽  
Jinhong Wei ◽  
Wenting Guo ◽  
Bo Sun ◽  
John Paul Estillore ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Stress Testing ◽  
Functional Characterization ◽  
Catecholaminergic Polymorphic Ventricular Tachycardia ◽  
Exercise Stress ◽  
Polymorphic Ventricular Tachycardia ◽  
Loss Of Function

Background: The overall objective of the present study is to extend our understanding of the clinical phenotype and underlying mechanism of a newly discovered cardiac arrhythmia syndrome through a multicenter study. Gain-of-function mutations in the cardiac Ca 2+ release channel (RyR2 [ryanodine receptor 2]) cause catecholaminergic polymorphic ventricular tachycardia, whereas loss-of-function RyR2 mutations are linked to a new cardiac arrhythmia disorder termed Ca 2+ -release deficiency syndrome (CRDS). Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmia disorder characterized by stress-induced bidirectional and polymorphic ventricular tachyarrhythmias and is routinely diagnosed by using exercise stress testing. Conversely, RyR2-CRDS is characterized by ventricular arrhythmias and sudden cardiac death but a negative exercise stress testing for catecholaminergic polymorphic ventricular tachycardia. There are currently no clinical diagnostic tests for CRDS and affected patients may manifest with sudden cardiac death as their first symptom. In the absence of effective clinical diagnostic tools, in vitro functional characterization of associated RyR2 mutations provides an alternative means to identify potential cases of CRDS. Methods: We searched for patients presenting with phenotypes compatible with CRDS that have RyR2 mutations and performed in vitro functional characterization. Results: We found that 3 novel (G570D, R4147K, and A4203V) and 2 previously reported (M4109R and A4204V) RyR2 mutations associated with CRDS phenotypes markedly reduced caffeine-induced Ca 2+ release and store overload-induced Ca 2+ release. We also characterized 2 additional loss-of-function RyR2 mutations previously reported (Q3925E and L4769S) that are located in the central and channel pore-forming domains critical for Ca 2+ activation and channel gating. Q3925E was identified through postmortem genetic testing in an individual who died suddenly, while L4769S is a variant of uncertain significance reported in ClinVar, suggesting that RyR2 CRDS may be under detected. Conclusions: These findings provide further support for the existence of an emerging RyR2 loss-of-function associated arrhythmia syndrome (CRDS) and shed new insights into the disease mechanism.

scholarly journals The Role of Flecainide in the Management of Catecholaminergic Polymorphic Ventricular Tachycardia

2016 ◽  
Vol 5 (1) ◽  
pp. 45 ◽  
Author(s):  
Krystien VV Lieve ◽  
◽  
Arthur A Wilde ◽  
Christian van der Werf ◽  
◽  
...  
Keyword(s):  
Heart Disease ◽  
Ventricular Tachycardia ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Structural Heart Disease ◽  
Current Data ◽  
Catecholaminergic Polymorphic Ventricular Tachycardia ◽  
Polymorphic Ventricular Tachycardia ◽  
Β Blockers

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder, with symptoms including syncope and sudden cardiac death due to polymorphic VT or ventricular fibrillation typically triggered by exercise or emotions in the absence of structural heart disease. The cornerstone of medical therapy for CPVT is β -blockers. However, recently flecainide has been added to the therapeutic arsenal for CPVT. In this review we summarise current data on the efficacy and role of flecainide in the treatment of CPVT.

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