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 Dealing with Sudden Cardiac Death: Who Deserves Device Implantation

2019 ◽  
Vol 5 (1 (P)) ◽  
pp. 12
Author(s):  
Dicky Armein Hanafy
Keyword(s):  
Heart Failure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Sudden Cardiac Death ◽  
Cardiac Arrhythmias ◽  
Cardiac Death ◽  
Cardiac Insufficiency ◽  
Resynchronization Therapy ◽  
Icd Implantation ◽  
Life Threatening

Sudden cardiac death is one of the leading causes of death in the western industrial nations. Most people are affected by coronary heart disease (coronary heart disease, CHD) or heart muscle (cardiomyopathy). These can lead to life-threatening cardiac arrhythmias. If the heartbeat is too slow due to impulse or conduction disturbances, cardiac pacemakers will be implanted. High-frequency and life-threatening arrhythmias of the ventricles (ventricular tachycardia, flutter or fibrillation) cannot be treated with a pacemaker. In such cases, an implantable cardioverter-defibrillator (ICD) is used, which additionally also provides all functions of a pacemaker. The implantation of a defibrillator is appropriate if a high risk of malignant arrhythmias has been established (primary prevention). If these life-threatening cardiac arrhythmias have occurred before and are not caused by a treatable (reversible) cause, ICD implantation will be used for secondary prevention. The device can stop these life-threatening cardiac arrhythmias by delivering a shock or rapid impulse delivery (antitachycardic pacing) to prevent sudden cardiac death. Another area of application for ICD therapy is advanced heart failure (heart failure), in which both main chambers and / or different wall sections of the left ventricle no longer work synchronously. This form of cardiac insufficiency can be treated by electrical stimulation (cardiac resynchronization therapy, CRT). Since the affected patients are also at increased risk for sudden cardiac death, combination devices are usually implanted, which combine heart failure treatment by resynchronization therapy and the prevention of sudden cardiac death by life-threatening arrhythmia of the heart chambers (CRT-D device). An ICD is implanted subcutaneously or under the pectoral muscle in the area of the left collarbone. Like pacemaker implantation, ICD implantation is a routine, low-complication procedure today.

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

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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