Role Of Ventricular Tachycardia Research Articles

LRP6-mediated phosphorylation of connexin43 in myocardial infarction

Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gαs) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gαs which played a role in VT of AMI.

CA-531-01 FAT INFILTRATION CONFERS PROPENSITY FOR VENTRICULAR TACHYCARDIA IN THE POST-INFARCT SUBSTRATE

Infiltrating adipose tissue (inFAT) is present in the post-infarct substrate, but its role in ventricular tachycardia (VT) arrhythmogenesis is not well-established. To investigate the role of post-infarct inFAT in VT propensity. 24 post-infarct patients who underwent VT ablation were prospectively enrolled across two centers. For each patient, contrast-enhanced computed tomography (CE-CT), late gadolinium-enhanced magnetic resonance imaging (LGE-MRI), and substrate mapping during sinus rhythm were acquired. Voltage amplitude, deceleration zones (DZ) which represent regions of activation slowing, and substrate-based ablation locations were compared with the inFAT and scar distributions. To glean deeper insights into arrhythmogenic propensity, novel hybrid digital heart twins representing the patient-specific inFAT from CT and scar from MRI were reconstructed. VT circuits were then induced, assessed, and compared to mapping data (Fig.A). Combined inFAT and scar had lower voltage and exhibited stronger correlations with voltage amplitude than that of scar alone (0.76±0.56 vs. 1.19±0.47 mV, p<0.0005; r = -0.54 vs. -0.45). inFAT and scar exhibited greater isochronal crowding than scar alone (3(2) vs. 2(1) isochrones, p<0.0005). Most DZs consisted of combined inFAT and scar (71.1%) rather than scar alone. The amount of ablated inFAT was strongly correlated with ablated scar (r = 0.734, p<0.05). In the digital hearts, 140 VTs were induced. The total amount of inFAT, but not scar, was significantly associated with the number of VTs induced (p<0.05). For most VT circuits, the critical isthmus was comprised of both inFAT and scar (110/140 VTs) (Fig.B). In a multivariate regression adjusting for age, infarct age, and VT circuit tissue volume, inFAT remodeling within the VT circuit, but not scar, was a predictor of the amount of DZs (β = 0.355, p<0.05) and clinical ablations (β = 0.323, p<0.005) (Fig.B). Post-infarct inFAT remodeling creates a critical arrhythmogenic substrate for VT that needs to be prioritized during ablation.

The Role of Ventricular Tachycardia in LVAD Patients and Clinical Outcomes

Introduction Ventricular tachycardia (VT) is common in patients with end-stage heart failure, and pose additional risks in patients who have left ventricular assist devices (LVAD). We set out to examine if development of VT increases risk of mortality post-LVAD and the odds of developing right ventricular failure (RVF). Hypothesis New onset VT increases both the risk of 1-year mortality post-LVAD and the odds of developing RVF. Methods We performed a single-center retrospective analysis of 295 patients who received a continuous-flow durable LVAD (HeartMate II or HeartWare VAD) between Jan. 1st 2006 through Dec. 31st 2016. We stratified patients to 2 cohorts: those who had positive or negative history of VT pre-LVAD and those who developed VT post-LVAD. A survival analysis based on 1-year survival was performed to find predictors of mortality and association with RVF. RVF severity was defined according to the new INTERMACS criteria. Results In patients with and without a history of VT, 113 (67%) and 74 (58%) respectively developed VT post-LVAD. Baseline characteristics were similar among all cohorts (Table 1). Survival analysis demonstrated that both new onset VT (Figure 1) and recurrence of VT did not increase the risk of 1 year mortality post-LVAD. Additionally, univariable analysis in patients without history of VT pre-LVAD showed that VT increased the odds of developing severe RVF (Table 2) (OR 6.20, p=0.020, 95%CI [1.33 - 29.0]), but this was no longer significant in multivariable analysis. Conclusions New onset and recurrent VT do not appear to be associated with increased mortality in LVAD patients. While there is a signal that new onset VT may increase the odds of severe RVF in patients without VT history pre-LVAD, this needs to be addressed prospectively and in larger cohorts.

Ventricular tachycardia in patients with type 1 myotonic dystrophy: a case series.

BackgroundType 1 myotonic dystrophy (DM1) is associated with a variety of cardiac conduction abnormalities and the frequent need for permanent pacing. However, the role of ventricular tachycardia (VT) and the implied risk of sudden cardiac death (SCD) is poorly understood.Case summaryThis study examined a 56-patient DM1 cohort of men and women, and identified five patients (two females and three males) with ventricular arrhythmias (8.9%). Patients were reviewed on a case-by-case basis, with their clinical presentation and management of VT and the associated cardiomyopathy indicated. Patient cardiac function was determined by 12-lead electrocardiogram, 48-h Holter monitor, and transthoracic echocardiography. These patients were therefore suitable candidates for implantable cardioverter-defibrillator implantation and received these devices; four of the five patients also received cardiac resynchronization therapy. Medical therapies included angiotensin converting enzyme inhibition, mineralocorticoid receptor antagonist, and following device implantation, beta-blocker therapy was initiated.DiscussionOur case series demonstrates the prevalence of VT in patients with DM1 highlighting the associated risks of SCD in this patient population. The burden of ventricular arrhythmias, advanced conduction disease, and cardiomyopathy are best treated with a combination of device and medical therapies.

Irregular Ventricular Tachycardia as a Mechanism of Stabilization of Mechanoelectrical Processes in Canine Heart under Conditions of Antiorthostatic Hypokinesia

We studied electrophysiological mechanisms of ventricular arrhythmias in dogs (n=7) under conditions of antiorthostatic hypokinesia (head-down tilt 45°). Abnormal transmural heterogeneity of repolarization in the base and apex of the left ventricle and increased dispersion of myocardial repolarization were revealed. By minute 30 of antiorthostatic hypokinesia, an increase in the duration of repolarization was revealed after a period of ventricular arrhythmia in all segments and regions of heart ventricles, which was accompanied by impairment of the pumping function of the heart. A hypothesis on the physiological role of ventricular tachycardia as a mechanism of electromechanical homeostatic stabilization in the heart was proposed. The obtained results suggest that under conditions of antiorthostatic hypokinesia, canine heart after a paroxysm of irregular ventricular tachycardia becomes more resistant to arrhythmia.

Can ventricular tachycardia non-inducibility after ablation predict reduced ventricular tachycardia recurrence and mortality in patients with non-ischemic cardiomyopathy? A meta-analysis of twenty-four observational studies

BackgroundAt present, the role of ventricular tachycardia (VT) non-inducibility after ablation in patients with non-ischemic cardiomyopathy (NICM) remains controversial. We conducted a meta-analysis of the published literature to assess whether VT non-inducibility after ablation could predict reduced VT recurrence and mortality in patients with NICM. MethodsPubMed, ScienceDirect, and the Cochrane library were searched for studies evaluating the effects of VT non-inducibility after catheter ablation on the long-term outcome in NICM patients with sustained VT. Results were analyzed using a fixed-effect model, and the data were pooled using RevMan 5.3 software. ResultsTwenty-four observational studies were identified (736 participants, mean follow-up time: 22months). NICM patients with VT inducibility after ablation had a higher risk of VT recurrence (odds ratio [OR]=5.83, 95% confidence interval [CI] 4.07–8.37; P<0.00001) and all-cause mortality (OR=3.55, 95% CI 1.62–7.78; P=0.002) compared with VT non-inducibility. Similarly in the subgroup analysis, patients with VT inducibility showed a higher risk of VT recurrence from non-ischemic dilated cardiomyopathy (OR=3.92, 95% CI 2.36–6.50; P<0.00001) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (OR=5.37, 95% CI 2.20–13.10; P=0.0002). Additionally, meta-analysis also showed that combined endo–epicardial ablation significantly reduced the risk of VT recurrence compared with endocardial-only ablation (OR=2.02, 95% CI 1.19–3.44; P=0.009; mean follow-up time: 22months). ConclusionRecent evidence has shown that VT non-inducibility after ablation is a predictor for reduced VT recurrence and mortality compared with VT inducibility in NICM patients with sustained VT. In addition, endocardial plus adjuvant epicardial ablation provides better long-term arrhythmia-free survival than endocardial ablation alone.

Triggers of Sustained Monomorphic Ventricular Tachycardia Differ Among Patients with Varying Etiologies of Left Ventricular Dysfunction

The mechanisms underlying the initiation of sustained ventricular tachycardia (VT) have not been fully elucidated. The extent to which reentry, abnormal automaticity, and triggered activity play a role in VT differs depending on the etiology of left ventricular dysfunction. By analyzing electrograms from implantable cardioverter defibrillator (ICD), we sought to determine whether there were differences in VT initiation patterns between patients with ischemic and nonischemic cardiomyopathy. We analyzed ICD electrograms in patients with ejection fractions < 40% who had sustained VT over a 27-month period. The trigger for VT onset was classified as a ventricular premature beat (VPB), supraventricular tachycardia, or of "sudden onset." The baseline cycle length, VT cycle length, coupling interval, and prematurity ratio were recorded for each event. The prematurity ratio was calculated as the coupling interval of the VT initiator divided by the baseline cycle length. Sixty-three VT events in 14 patients met the inclusion criteria. A VPB initiated the VT in 58 episodes (92%), 1 episode (2%) was initiated by a supraventricular tachycardia, and 4 episodes (6%) were sudden onset. The prematurity ratio was significantly higher (P < 0.05) in patients with ischemic cardiomyopathy (0.751 +/- 0.068) as compared to patients with nonischemic cardiomyopathy (0.604 +/- 0.139). VPBs initiated most sustained VT episodes. A significantly higher prematurity ratio was observed in the ischemic heart disease group. This may represent different mechanisms of VT initiation in patients with ischemic versus nonischemic heart disease.