scholarly journals Evaluation of Genes Encoding for the Transient Outward Current (Ito) Identifies the KCND2 Gene as a Cause of J-Wave Syndrome Associated With Sudden Cardiac Death

2014 ◽  
Vol 7 (6) ◽  
pp. 782-789 ◽  
Author(s):  
Mark J. Perrin ◽  
Arnon Adler ◽  
Sharon Green ◽  
Foad Al-Zoughool ◽  
Petro Doroshenko ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Outward Current ◽  
Transient Outward Current ◽  
Genes Encoding ◽  
J Wave

scholarly journals Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death

2012 ◽  
Vol 113 (11) ◽  
pp. 1772-1783 ◽  
Author(s):  
Ingrid M. Bonilla ◽  
Andriy E. Belevych ◽  
Arun Sridhar ◽  
Yoshinori Nishijima ◽  
Hsiang-Ting Ho ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Cardiac Death ◽  
Outward Current ◽  
Calcium Handling ◽  
Transient Outward Current ◽  
Cellular Electrophysiology ◽  
Endurance Exercise Training

The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171–H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period ( n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization ( P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group ( P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K+ current, which was restored by exercise training ( P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training ( P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling.

Common RyR2 variants associate with ventricular arrhythmias and sudden cardiac death in chronic heart failure

2010 ◽  
Vol 119 (5) ◽  
pp. 215-226 ◽  
Author(s):  
Yuqin Ran ◽  
Jingzhou Chen ◽  
Ning Li ◽  
Weili Zhang ◽  
Li Feng ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Chronic Heart Failure ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Protective Factor ◽  
Critical Role ◽  
Functional Variants ◽  
Increased Risk ◽  
Genes Encoding

Ca2+ cycling plays a critical role in heart failure and lethal arrhythmias. As susceptibility to sudden cardiac death is considered to be a heritable trait in general population, we have therefore investigated whether potentially functional variants of genes encoding RyR2 (ryanodine receptor 2) and the L-type Ca2+ channel are related to the risk of ventricular arrhythmias and sudden cardiac death in CHF (chronic heart failure) in a case-control study. We found that the A allele of rs3766871 in RYR2 was associated with an increased risk of ventricular arrhythmias in patients with CHF {odds ratio, 1.66 [95% CI (confidence interval), 1.21–2.26]; P=0.002}. During a median follow-up period of 32 months in 1058 (85.0%) patients, 296 (28.0%) patients died from heart failure, of whom 141 (47.6%) had sudden cardiac death. After adjustment for age, gender and suspected risk factors, patients carrying the A allele of rs3766871 had an increased risk of cardiac death {HR (hazard ratio), 1.53 [95% CI, 1.11–2.12]; P=0.010} and sudden cardiac death [HR, 1.92 (95% CI, 1.25–2.94); P=0.003]. Patients carrying the A allele of rs790896 in RYR2 had a reduced risk of sudden cardiac death [HR, 0.65 (95% CI, 0.45–0.92); P=0.015]. In conclusion, the A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias, but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with CHF.

Elimination of allosteric modulation of myocardial KATP channels by ATP and protons in two Kir6.2 polymorphisms found in sudden cardiac death

2006 ◽  
Vol 25 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Ningren Cui ◽  
Li Li ◽  
Xueren Wang ◽  
Yun Shi ◽  
Weiwei Shi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Single Channel ◽  
Allosteric Regulation ◽  
Point Mutations ◽  
Outward Current ◽  
Katp Channels ◽  
Intracellular Atp

The major cause of sudden cardiac death (SCD) is ventricular arrhythmias due to unstable myocardial electrical activity in which the ATP-sensitive K+ (KATP) channels play a role. Genetic disruption of these channels predisposes the myocardium to arrhythmias. Two point mutations in the Kir6.2 subunit are found in SCD with acute myocardial infarction. Here we show evidence for the functional consequences of the P266T and R371H variants. Baseline single-channel properties, expression density, and channel modulations were studied in patch clamp. We focused on channel modulations by intracellular ATP and protons, as the concentration of these two important KATP channel regulators changes widely with hypoxic ischemia. We found that both variants expressed functional currents even though they occur at two highly conserved regions. The open state probability of P266T was twice as high as the wild-type (WT) channel, whereas its channel density was only ∼20% of the WT channel. Although the outward current was not affected by these two mutations at neutral pH, it was ∼20% lower at acidic pH in the P266T than in the WT channel. Both P266T and R371H mutations significantly reduced ATP sensitivity and increased pH sensitivity. More dramatically, allosteric regulation by intracellular ATP and protons was almost completely eliminated in the polymorphic P266T and R371H channels. Such an abnormality was seen in both inward and outward currents. Given the importance and beneficial effects of allosteric regulation in cellular responses to metabolic stress, the loss of such a regulatory mechanism in the P266T and R371H variants appears consistent with the adverse consequences occurring during acute myocardial infarction in patients.

A Genetic Variant in DPP10 Linked to Inherited J-Wave Syndrome Associated with Sudden Cardiac Death by Augmentation of Kv4.3 Channel Current

Heart Rhythm ◽  
2012 ◽  
Vol 9 (11) ◽  
pp. 1919-1920 ◽  
Author(s):  
H. Barajas-Martinez ◽  
D. Hu ◽  
R. Pfeiffer ◽  
E. Burashnikov ◽  
A. Powers ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Genetic Variant ◽  
Channel Current ◽  
J Wave

scholarly journals Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death

Heart Rhythm ◽  
2010 ◽  
Vol 7 (12) ◽  
pp. 1872-1882 ◽  
Author(s):  
Elena Burashnikov ◽  
Ryan Pfeiffer ◽  
Héctor Barajas-Martinez ◽  
Eva Delpón ◽  
Dan Hu ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Calcium Channel ◽  
Cardiac Death ◽  
J Wave

scholarly journals J Wave Inferior Leads-A New ECG Predictor of Sudden Cardiac Death in Chronic Heart Failure

2011 ◽  
Vol 27 (Supplement) ◽  
pp. OP67_2
Author(s):  
Pei Juanhui ◽  
Pu Jielin ◽  
Chen Jingzhou ◽  
Zhang Yinhui
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Chronic Heart Failure ◽  
Cardiac Death ◽  
J Wave

Early repolarization pattern and syndrome — norm or pathology?

2020 ◽  
pp. 38-41
Author(s):  
A. L. Bobrov
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Structural Heart Disease ◽  
Polymorphic Ventricular Tachycardia ◽  
Early Repolarization ◽  
Multicenter Studies ◽  
St Segment ◽  
Increased Risk ◽  
Ecg Leads ◽  
J Wave

The review article is devoted to the diagnosis and clinical significance of early ventricular repolarization phenomenon and syndrome. Just 13 years ago, the phenomenon was recognized as an unambiguous version of the norm. However, the results of a series of multicenter studies have shown that the phenomenon is associated with an increased risk of sudden cardiac death. The following criteria are recognized as criteria for early repolarization: the presence of a notch or a junction wave on the descending part of the R wave with a concomitant (or absent) elevation of the ST segment (at the Jt point); J wave (point) ≥0.1mV peak elevation (at Jp point) in ≥2 adjacent 12-channel ECG leads, except for V1–3 leads; QRS duration, measured in leads with J wave (point) <120 ms. Early repolarization syndrome is a clinical condition involving a combination of the pattern of early repolarization and polymorphic ventricular tachycardia, ventricular fibrillation and/or sudden cardiac death in persons without structural heart disease. Treatment is required in patients with a symptom of ventricular tacharrhythmia or family history early repolarization with sudden cardiac death.

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