Risk Of Ventricular Tachycardia Research Articles

Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show tremendous promise for cardiac regeneration following myocardial infarction (MI), but their transplantation gives rise to transient ventricular tachycardia (VT) in large-animal MI models, representing a major hurdle to translation. Our group previously reported that these arrhythmias arise from a focal mechanism whereby graft tissue functions as an ectopic pacemaker; therefore, we hypothesized that hPSC-CMs engineered with a dominant negative form of the pacemaker ion channel HCN4 (dnHCN4) would exhibit reduced automaticity and arrhythmogenic risk following transplantation. We used CRISPR/Cas9-mediated gene-editing to create transgenic dnHCN4 hPSC-CMs, and their electrophysiological behavior was evaluated in vitro by patch-clamp recordings and optical mapping. Next, we transplanted WT and homozygous dnHCN4 hPSC-CMs in a pig MI model and compared post-transplantation outcomes including the incidence of spontaneous arrhythmias and graft structure by immunohistochemistry. In vitro dnHCN4 hPSC-CMs exhibited significantly reduced automaticity and pacemaker funny current (I f ) density relative to wildtype (WT) cardiomyocytes. Following transplantation with either dnHCN4 or WT hPSC-CMs, all recipient hearts showed transmural infarct scar that was partially remuscularized by scattered islands of human myocardium. However, in contrast to our hypothesis, both dnHCN4 and WT hPSC-CM recipients exhibited frequent episodes of ventricular tachycardia (VT). While genetic silencing of the pacemaker ion channel HCN4 suppresses the automaticity of hPSC-CMs in vitro, this intervention is insufficient to reduce VT risk post-transplantation in the pig MI model, implying more complex mechanism(s) are operational in vivo.

Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias

BackgroundHuman pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show tremendous promise for cardiac regeneration following myocardial infarction (MI), but their transplantation gives rise to transient ventricular tachycardia (VT) in large-animal MI models, representing a major hurdle to translation. Our group previously reported that these arrhythmias arise from a focal mechanism whereby graft tissue functions as an ectopic pacemaker; therefore, we hypothesized that hPSC-CMs engineered with a dominant negative form of the pacemaker ion channel HCN4 (dnHCN4) would exhibit reduced automaticity and arrhythmogenic risk following transplantation.MethodsWe used CRISPR/Cas9-mediated gene-editing to create transgenic dnHCN4 hPSC-CMs, and their electrophysiological behavior was evaluated in vitro by patch-clamp recordings and optical mapping. Next, we transplanted WT and homozygous dnHCN4 hPSC-CMs in a pig MI model and compared post-transplantation outcomes including the incidence of spontaneous arrhythmias and graft structure by immunohistochemistry.ResultsIn vitro dnHCN4 hPSC-CMs exhibited significantly reduced automaticity and pacemaker funny current (If) density relative to wildtype (WT) cardiomyocytes. Following transplantation with either dnHCN4 or WT hPSC-CMs, all recipient hearts showed transmural infarct scar that was partially remuscularized by scattered islands of human myocardium. However, in contrast to our hypothesis, both dnHCN4 and WT hPSC-CM recipients exhibited frequent episodes of ventricular tachycardia (VT).ConclusionsWhile genetic silencing of the pacemaker ion channel HCN4 suppresses the automaticity of hPSC-CMs in vitro, this intervention is insufficient to reduce VT risk post-transplantation in the pig MI model, implying more complex mechanism(s) are operational in vivo.

Computed tomography as a predictive tool for ventricular tachycardia

Abstract Background Sudden cardiac death is the main cause of mortality worldwide. It is often linked with ventricular tachycardia (VT). To prevent VT, high-risk patients are typically equipped with intracardiac defibrillators (ICDs). Currently, left ventricular ejection fraction (LVEF) is the standard for determining a patient's risk level. Objective We hypothesized that the use of imaging software analyzing cardiac CT-scans could enhance the detection of patients with an increased risk of VT. Methods and Results In this study, 132 patients with ischemic cardiomyopathy (average age 66.2±11.4 years, with an average LVEF of 36.6±10.3%), all with implanted cardiac devices, underwent CT scans. We developed software to automatically analyze the heart's wall tissue thickness, cardiac fat, and calcification levels (Figure.1.A). A viable cardiac wall thickness of less than 3mm typically indicates a ventricular wall predominantly composed of scar tissue with minimal viable tissue remaining. In contrast, a viable wall thickness of less than 5mm includes regions with more viable tissue and therfore represents the total scar. Over an average follow-up of 6.6 years (79.8 ± 30.5 months) via live telemedicine, we observed that patients with VT had a significant difference in wall thickness ratio (3mm/5mm; no VT 0.31±0.18 vs, VT 0.44±0.18, p<0.01)) and higher calcification (0.10±0.38ml vs. 0.47±1.57ml, p=0.039). The amount of cardiac fat did not significantly differ between the no VT and VT groups (1.14±1.38ml vs.1.21±1.01ml, p=0.771). Logistic regression determined a critical cutoff for wall thickness at a ratio of 0.3 for 3mm and 5mm thickness. Kaplan Meyer analysis contrasted this wall thickness ratio of 0.3 (figure.1.B) against the established LVEF threshold of 35% (figure.1.C) for predicting VT-free survival, revealing a notable disparity favoring wall thickness ratio (p<0.01) over LVEF (p=0.77). Conclusions The findings suggest that a higher proportion of regions of thin viable tissue or dense scar in the total scar is a more effective predictor of VT-free survival than LVEF, potentially improving the identification of patients at risk for sudden cardiac death.Figure. 1

Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI

Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). To evaluate the risk of late VT and VF after primary PCI for STEMI. This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.

Effects of ranolazine on the arrhythmic substrate in hypertrophic cardiomyopathy.

Introduction: Hypertrophic cardiomyopathy (HCM) is a leading cause of lethal arrhythmias in the young. Although the arrhythmic substrate has been hypothesised to be amenable to late Na+ block with ranolazine, the specific mechanisms are not fully understood. Therefore, this study aimed to investigate the substrate mechanisms of safety and antiarrhythmic efficacy of ranolazine in HCM. Methods: Computational models of human tissue and ventricles were used to simulate the electrophysiological behaviour of diseased HCM myocardium for variable degrees of repolarisation impairment, validated against in vitro and clinical recordings. S1-S2 pacing protocols were used to quantify arrhythmic risk in scenarios of (i) untreated HCM-remodelled myocardium and (ii) myocardium treated with 3µM, 6µM and 10µM ranolazine, for variable repolarisation heterogeneity sizes and pacing rates. ECGs were derived from biventricular simulations to identify ECG biomarkers linked to antiarrhythmic effects. Results: 10µM ranolazine given to models manifesting ventricular tachycardia (VT) at baseline led to a 40% reduction in number of VT episodes on pooled analysis of >40,000 re-entry inducibility simulations. Antiarrhythmic efficacy and safety were dependent on the degree of repolarisation impairment, with optimal benefit in models with maximum JTc interval <370ms. Ranolazine increased risk of VT only in models with severe-extreme repolarisation impairment. Conclusion: Ranolazine efficacy and safety may be critically dependent upon the degree of repolarisation impairment in HCM. For moderate repolarisation impairment, reductions in refractoriness heterogeneity by ranolazine may prevent conduction blocks and re-entry. With severe-extreme disease substrates, reductions of the refractory period can increase re-entry sustainability.

Strain-controlled electrophysiological wave propagation alters in silico scar-based substrate for ventricular tachycardia.

Introduction: Assessing a patient's risk of scar-based ventricular tachycardia (VT) after myocardial infarction is a challenging task. It can take months to years after infarction for VT to occur. Also, if selected for ablation therapy, success rates are low. Methods: Computational ventricular models have been presented previously to support VT risk assessment and to provide ablation guidance. In this study, an extension to such virtual-heart models is proposed to phenomenologically incorporate tissue remodeling driven by mechanical load. Strain amplitudes in the heart muscle are obtained from simulations of mechanics and are used to adjust the electrical conductivity. Results: The mechanics-driven adaptation of electrophysiology resulted in a more heterogeneous distribution of propagation velocities than that of standard models, which adapt electrophysiology in the structural substrate from medical images only. Moreover, conduction slowing was not only present in such a structural substrate, but extended in the adjacent functional border zone with impaired mechanics. This enlarged the volumes with high repolarization time gradients (≥10ms/mm). However, maximum gradient values were not significantly affected. The enlarged volumes were localized along the structural substrate border, which lengthened the line of conduction block. The prolonged reentry pathways together with conduction slowing in functional regions increased VT cycle time, such that VT was easier to induce, and the number of recommended ablation sites increased from 3 to 5 locations. Discussion: Sensitivity testing showed an accurate model of strain-dependency to be critical for low ranges of conductivity. The model extension with mechanics-driven tissue remodeling is a potential approach to capture the evolution of the functional substrate and may offer insight into the progression of VT risk over time.

Ventricular Tachycardia in Patients With Peripartum Cardiomyopathy: Prevalence, Predictors, and Associated In-Hospital Adverse Events.

Introduction The purpose of this study was to determine the prevalence of ventricular tachycardia (VT) among patients admitted with peripartum cardiomyopathy (PPCM) as well as to analyze the independent association of VT with in-hospital outcomes among PPCM patients. Methods Data were obtained from the National Inpatient Sample from January 2016 to December 2019. We assessed predictors of VT in patients admitted with PPCM. We also assessed the independent association of VT with clinical outcomes among patients admitted with PPCM. Results From 2016 to 2019, 4730 patients with PPCM were reported to the national inpatient sample database, 309 of which developed VT (6.5%). Using multivariate analysis, we found predictors of VT to include patient characteristics and factors such as age (adjusted OR (aOR)=1.020, p=0.023), chronic kidney disease (aOR=1.440, p=0.048), coagulopathy (aOR=1.964, p=0.006), and atrial fibrillation (aOR=3.965,p<0.001). Conversely, pre-eclampsia was significantly associated with a decreased risk of VT in PPCM patients (aOR=0.218,p=0.001). Conclusion In a large cohort of patients admitted with peripartum cardiomyopathy, we found the prevalence of VT to be 6.5%. Risk factors for VT in this patient population included conditions such as coagulopathy and atrial fibrillation.

Catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy and biventricular involvement.

Catheter ablation of ventricular tachycardia (VT) improves VT-free survival in 'classic' arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to investigate electrophysiological features and ablation outcomes in patients with ARVC and biventricular (BiV) involvement. We assembled a retrospective cohort of definite ARVC cases with sustained VTs. Patients were divided into the BiV (BiV involvement) group and the right ventricular (RV) (isolated RV involvement) group based on the left ventricular systolic function detected by cardiac magnetic resonance. All patients underwent electrophysiological mapping and VT ablation. Acute complete success was non-inducibility of any sustained VT, and the primary endpoint was VT recurrence. Ninety-eight patients (36 ± 14 years; 87% male) were enrolled, including 50 in the BiV group and 48 in the RV group. Biventricular involvement was associated with faster clinical VTs, a higher VT inducibility, and more extensive arrhythmogenic substrates (all P < 0.05). Left-sided VTs were observed in 20% of the BiV group cases and correlated with significantly reduced left ventricular systolic function. Catheter ablation achieved similar acute efficacy between these two groups, whereas the presence of left-sided VTs increased acute ablation failure (40 vs. 5%, P = 0.012). Over 51 ± 34 months [median, 48 (22-83) months] of follow-up, cumulative VT-free survival was 52% in the BiV group and 58% in the RV group (P = 0.353). A multivariate analysis showed that younger age, lower RV ejection fraction (RVEF), and non-acute complete ablation success were associated with VT recurrence in the BiV group. Biventricular involvement implied a worse arrhythmic phenotype and increased the risk of left-sided VTs, while catheter ablation maintained its efficacy for VT control in this population. Younger age, lower RVEF, and non-acute complete success predicted VT recurrence after ablation.

Management of ventricular tachycardias: insights on centre settings, procedural workflow, endpoints, and implementation of guidelines-results from an EHRA survey.

Ventricular tachycardia (VT), and its occurrence, is still one of the main reasons for sudden cardiac death and, therefore, for increased mortality and morbidity foremost in patients with structural heart [Kahle A-K, Jungen C, Alken F-A, Scherschel K, Willems S, Pürerfellner H et al. Management of ventricular tachycardia in patients with ischaemic cardiomyopathy: contemporary armamentarium. Europace 2022;24:538-51]. Catheter ablation has become a safe and effective treatment option in patients with recurrent VT [Cronin EM, Bogun FM, Maury P, Peichl P, Chen M, Namboodiri N et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020;17:e2-154]. Previous and current guidelines provide guidance on indication for VT ablation and risk assessment and evaluation of underlying disease. However, no uniform recommendation is provided regarding procedural strategies, timing of ablation, and centre setting. Therefore, these specifics seem to differ largely, and recent data are sparse. This physician-based European Heart Rhythm Association survey aims to deliver insights on not only infrastructural settings but also procedural specifics, applied technologies, ablation strategies, and procedural endpoints. Therefore, these findings might deliver a real-world scenario of VT management and potentially are of guidance for other centres.

Influence of standard modifiable risk factors on ventricular tachycardia after myocardial infarction

Abstract Background Sudden cardiac death due to ventricular tachyarrhythmia is the single greatest cause of death within two years after myocardial infarction (MI), especially early in the first 30 days. Purpose We aimed to assess the incidence of inducible ventricular tachycardia (VT) early after MI in those with standard modifiable risk factors (SMuRFs) versus those without. Methods Consecutive patients with LVEF ≤40% on day 3–5 after ST elevation myocardial infarction (STEMI) who underwent electrophysiology study were prospectively recruited. Positive EPS was defined as sustained monomorphic VT cycle length ≥200ms for &amp;gt; 10 seconds, or shorter duration if hemodynamic compromise occurred. The primary outcomes were inducibility of VT and all-cause mortality. Results A total of 410 patients, of which 126 had inducible VT on EPS, early after myocardial infarction were included. In our multiple regressions model, when smoking history was considered, ex-smokers were identified at increased risk of VT at EPS (adjusted OR 2.0, p=0.033) whilst those who never smoked or were current smokers had comparable risk. It also showed that the presence of any SMuRF apart from current smoker also conferred an increased risk of inducible VT (adjusted OR 1.9, p=0.043). For every 10 years increase in age the risk of death increased by a multiplicative factor of 1.3, for every 10% decrease in LVEF (%) the risk of death increased by a multiplicative factor of 1.9 and in patients with previous IHD, the risk of death was doubled. Neither the number of SMuRFs nor the presence of any SMuRF were associated with mortality. Conclusion In our cohort of patients with LVEF&amp;lt;40% early after STEMI who had an EPS to assess for inducible VT, either the presence of any of the three SMuRFs (hypertension, hypercholesterolemia or diabetes mellitus) or previous smoking doubled the chance of having VT induced. These data provide valuable information that could be integrated into clinical care protocols after myocardial infarction to improve long-term patient outcomes and further reinforces the need to modify SMuRFs in patients with ischemic heart disease.

Abstract 13943: Comparison of the Frequency and Time to True Ventricular Tachycardia Among Patients in the Cardiac, Medical/Surgical and Neurologic Intensive Care Units

Introduction: Continuous ECG monitoring is the non-invasive gold standard used to identify ventricular tachycardia (VT), yet 87% of current bedside monitor VTs could be false. Therefore, knowing the burden of true VT is essential to guide treatment to those at greatest risk of poor outcomes. Hypothesis: When stratifying by intensive care unit (ICU) (cardiac, medical/surgical, neurological), there will be differences in: 1) demographic and clinical characteristics of patients with true VT; and 2) frequency and time to first true VT. Methods: Retrospective cohort study of adults admitted to an academic medical center ICU, 9/13-4/15. Potential VTs among 5,679 consecutive ICU patients were manually annotated by clinicians as true/false. Patient-level data were extracted from the health record. We used Kaplan-Meier and Cox proportional hazards methods to calculate time to first true VT and 60-day VT rate by ICU type. Results: There were differences in all characteristics examined (p&lt;0.0001)(Table) and frequency of true VT, stratified by ICU type (log-rank p&lt;0.0001)(Figure). After adjustment for age, gender, and risk factors (Table), CICU patients had a 42% increased rate (HR 1.42, 95% CI 1.16-1.74) and NICU patients had a 28% decreased rate of VT (HR 0.72, 95% CI 0.59-0.89) compared to M/SICU patients. Conclusion: Patients in the CICU experienced true VT much earlier (1.5 days) after admission than patients in the M/SICU and NICU. In addition, CICU patients had a higher rate of true VT and associated VT risk factors as compared to M/SICU and NICU patients. As expected, known cardiac risk factors are associated with true VT, but may be hidden among false alarms during bedside monitoring.

Influence of standard modifiable risk factors on ventricular tachycardia after myocardial infarction

BackgroundInducible ventricular tachycardia (VT) at electrophysiology study (EPS) predicts sudden cardiac death because of ventricular tachyarrhythmia, the single greatest cause of death within 2 years after myocardial infarction (MI).ObjectivesWe aimed to assess the association between standard modifiable risk factors (SMuRFs) and inducible VT at EPS early after MI.MethodsConsecutive patients with left ventricle ejection fraction ≤40% on days 3–5 after ST elevation MI (STEMI) who underwent EPS were prospectively recruited. Positive EPS was defined as induced sustained monomorphic VT cycle length ≥200 ms for ≥10 s or shorter if hemodynamically compromised. The primary outcome was inducibility of VT at EPS, and the secondary outcome was all-cause mortality on follow-up.ResultsIn 410 eligible patients undergoing EPS soon (median of 9 days) after STEMI, 126 had inducible VT. Ex-smokers experienced an increased risk of inducible VT [multivariable logistic regression adjusted odds ratio (OR) 2.0, p = 0.033] compared with current or never-smokers, with comparable risk. The presence of any SMuRFs apart from being a current smoker conferred an increased risk of inducible VT (adjusted OR 1.9, p = 0.043). Neither the number of SMuRFs nor the presence of any SMuRFs was associated with mortality at a median follow-up of 5.4 years.ConclusionsIn patients with recent STEMI and impaired left ventricular function, the presence of any SMuRFs, apart from being a current smoker, conferred an increased risk of inducible VT at EPS. These results highlight the need to modify SMuRFs in this high-risk subset of patients.

QRS Duration After Pulmonary Valve Replacement in Adults with Repaired Tetralogy of Fallot: Association with Ventricular Arrhythmia and Correlation with Right Ventricular Size.

The aim of this study is to analyze the relationship between QRS duration after pulmonary valve replacement (PVR) and ventricular arrhythmias (VA) in patients with repaired tetralogy of Fallot (ToF). ToF patients may face complications such as heart failure and VA after primary repair, often mitigated by PVR. Prior studies have shown a decrease in QRS duration and right ventricular (RV) size following PVR. It remains unclear whether a lack of QRS duration reduction identifies patients at risk of VA. We retrospectively identified adult patients with repaired ToF who underwent surgical or transcatheter PVR. EKG data (pre-PVR, 30 days to 1-year post-PVR, and closest to CMR) was collected. The primary endpoint was sustained ventricular tachycardia (VT), ICD shock for sustained VT, or inducible VT on EP study. 85 patients were included (median follow-up 3.6 years; median age 34 years; 51% females). The primary outcome was noted in 8 patients. Mean QRS duration decreased by 5 ms following PVR (p = 0.0001). Increased age at PVR, QRS ≥ 180 ms post-PVR, no reduction in QRS after PVR, and a history of VT were associated with higher risk of the primary endpoint. The change in QRS was linearly correlated with the change in RVEDVi (R = 0.66). Adults with repaired ToF experience a reduction in QRS duration post-PVR that correlates with the change of the RV size. Patients with QRS ≥ 180 ms post-PVR, no reduction in QRS, increased age at repair, and a history of VT are at risk for recurrent VT and warrant closer monitoring/ICD consideration.

Ventricular tachycardia risk prediction with an abbreviated duration mobile cardiac telemetry.

Ventricular tachycardia (VT) occurs intermittently, unpredictably, and has potentially lethal consequences. Our aim was to derive a risk prediction model for VT episodes ≥10 beats detected on 30-day mobile cardiac telemetry based on the first 24 hours of the recording. We included patients who were monitored for 2 to 30 days in the United States using full-disclosure mobile cardiac telemetry, without any VT episode ≥10 beats on the first full recording day. An elastic net prediction model was derived for the outcome of VT ≥10 beats on monitoring days 2 to 30. Potential predictors included age, sex, and electrocardiographic data from the first 24 hours: heart rate; premature atrial and ventricular complexes occurring as singlets, couplets, triplets, and runs; and the fastest rate for each event. The population was randomly split into training (70%) and testing (30%) samples. In a population of 19,781 patients (mean age 65.3±17.1 years, 43.5% men), with a median recording time of 18.6 ± 9.6 days, 1510 patients had at least 1 VT ≥10 beats. The prediction model had good discrimination in the testing sample (area under the receiver-operating characteristic curve 0.7584, 95% confidence interval 0.7340-0.7829). A model excluding age and sex had an equally good discrimination (area under the receiver-operating characteristic curve 0.7579, 95% confidence interval 0.7332-0.7825). In the top quintile of the score, more than 1 in 5 patients had a VT ≥10 beats, while the bottom quintile had a 98.2% negative predictive value. Our model can predict risk of VT ≥10 beats in the near term using variables derived from 24-hour electrocardiography, and could be used to triage patients to extended monitoring.

Effects of Mesenchymal Stem Cell Injection into Healed Myocardial Infarction Scar Border Zone on the Risk of Ventricular Tachycardia.

The scar border zone is a main source of reentry responsible for ischemic ventricular tachycardia (VT). We evaluated the effects of mesenchymal stem cell (MSC) injection into the scar border zone on arrhythmic risks in a post-myocardial infarction (MI) animal model. Rabbit MI models were generated by left descending coronary artery ligation. Surviving rabbits after 4 weeks underwent left thoracotomy and autologous MSCs or phosphate-buffered saline (PBS) was administered to scar border zones in two rabbits in each group. Another rabbit without MI underwent a sham procedure (control). An implantable loop recorder (ILR) was implanted in the left chest wall in all animals. Four weeks after cell injections, ventricular fibrillation was induced in 1/2 rabbit in the PBS group by electrophysiologic study, and no ventricular arrhythmia was induced in the MSC group or control. Spontaneous VT was not detected during ILR analysis in any animal for 4 weeks. Histologic examination showed restoration of connexin 43 (Cx43) expression in the MSC group, which was higher than in the PBS group and comparable to the control. In conclusion, MSC injections into the MI scar border zone did not increase the risk of VT and were associated with favorable Cx43 expression and arrangement.

RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease

Diastolic Ca2+ leak due to cardiac ryanodine receptor (RyR2) hyperactivity has been widely documented in chronic ischemic heart disease (CIHD) and may contribute to ventricular tachycardia (VT) risk and progressive left-ventricular (LV) remodeling. Here we test the hypothesis that targeting RyR2 hyperactivity can suppress VT inducibility and progressive heart failure in CIHD by the RyR2 inhibitor dantrolene. Methods and resultsCIHD was induced in C57BL/6 J mice by left coronary artery ligation. Four weeks later, mice were randomized to either acute or chronic (6 weeks via implanted osmotic pump) treatment with dantrolene or vehicle. VT inducibility was assessed by programmed stimulation in vivo and in isolated hearts. Electrical substrate remodeling was assessed by optical mapping. Ca2+ sparks and spontaneous Ca2+ releases were measured in isolated cardiomyocytes. Cardiac remodeling was quantified by histology and qRT-PCR. Cardiac function and contractility were measured using echocardiography. Compared to vehicle, acute dantrolene treatment reduced VT inducibility. Optical mapping demonstrated reentrant VT prevention by dantrolene, which normalized the shortened refractory period (VERP) and prolonged action potential duration (APD), preventing APD alternans. In single CIHD cardiomyocytes, dantrolene normalized RyR2 hyperactivity and prevented spontaneous intracellular Ca2+ release. Chronic dantrolene treatment not only reduced VT inducibility but also reduced peri-infarct fibrosis and prevented further progression of LV dysfunction in CIHD mice. ConclusionsRyR2 hyperactivity plays a mechanistic role for VT risk, post-infarct remodeling, and contractile dysfunction in CIHD mice. Our data provide proof of concept for the anti-arrhythmic and anti-remodeling efficacy of dantrolene in CIHD.

Inducibility of Multiple Ventricular Tachycardia's during a Successful Ablation Procedure Is a Marker of Ventricular Tachycardia Recurrence.

Even after a successful ventricular tachycardia ablation (VTA), some patients have recurrent ventricular tachycardia (VT) during their follow-up. We assessed the long-term predictors of recurrent VT after having a successful VTA. The patients who underwent a successful VTA (defined as the non-inducibility of any VT at the procedure's end) in 2014-2021 at our center in Israel were retrospectively analyzed. A total of 111 successful VTAs were evaluated. Out of them, 31 (27.9%) had a recurrent event of VT after the procedure during a median follow-up time of 264 days. The mean left ventricular ejection fraction (LVEF) was significantly lower among patients with recurrent VT events (28.9 ± 12.67 vs. 23.53 ± 12.224, p = 0.048). A high number of induced VTs (>two) during the procedure was found to be a significant predictor of VT recurrence (24.69% vs. 56.67%, 20 vs. 17, p = 0.002). In a multivariate analysis, a lower LVEF (HR, 0.964; p = 0.037) and a high number of induced VTs (HR, 2.15; p = 0.039) were independent predictors of arrhythmia recurrence. The inducibility of more than two VTs during a VTA procedure remains a predictor of VT recurrence even after a successful VT ablation. This group of patients remains at high risk for VT and should be followed up with and treated more vigorously.

Dysrhythmic profile of inotropic therapy in patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with acute coronary syndrome (ACS) may develop ventricular dysfunction and need to use drugs with a positive inotropic effect, during the acute phase. Despite the hemodynamic benefit of the use of these drugs, positive inotropic drugs may have several side effects, including ventricular tachycardia (VT)and atrial fibrillation (AF). AF can complicate the management of patients with ACS, since these patients need intense antiplatelet therapy, and in the case of AF, it may have to be associated with anticoagulant therapy, thereby increasing the bleeding risk. The clinical significance of AF during an acute event remains to be ascertained. Purpose This study aims to assess the frequency of occurrence of dysrhythmic complications with the use of positive inotropic drugs in patients hospitalized for ACS. Methods We performed a 6-year retrospective, observational, multicenter study. We included patients with ACS who used positive or not inotropic drugs during hospitalization, dividing the sample into two groups respectively (Group 1 and Group 2). Between the two groups we compared the occurrence of ventricular tachycardia and atrial fibrillation. In addition, we performed an analysis for the use of levosimendan. Results We analyzed a sample of 5860 patients. Of these, 70.3% were male. In Group 1 we included 377 patients and in Group 2 5329 patients. The occurrence of VT in Group 1 was higher than in Group 2 (15.5% vs 1.6%; p&amp;lt;0.001; OR: 11.472; 95% CI [8.212;16.027]). The rate of occurrence of AF in Group 1 was higher than in Group 2 (19.3% vs 5.1%; p&amp;lt;0.001; OR:4.413; 95% CI [3.388;5.749]). Regarding the use of levosimendan, 50 patients were analyzed. VT was more frequent with the use of this drug than without it (18.0% vs 2.5%; p&amp;lt;0.001; OR: 8.576 95% CI [4.092;17.976]). Atrial fibrillation was more frequent with levosimendan use than with no use (34.0% vs 6.0%; p&amp;gt;0.001; OR: 8.137; 95% CI [4.487;14.754]). Conclusion Arrhythmic complications were much more frequent in the group that used positive inotropic drugs, namely VT and AF. Levosimendan stands out, related to the increase in the occurrence of AF and the remaining inotropes with an increased risk of VT. These arrhythmic complications pose a challenge in the management of these patients, as in patients with ACS, the use of Levosimendan is associated with more episodes of AF, and might complicate the antithrombotic therapy strategy choice.

PO-05-193 PREVALENCE OF ARRHYTHMIAS AND CARDIAC CONDUCTION DISEASE IN PATIENTS WITH LEFT VENTRICULAR ASSIST DEVICE

Left ventricular assist devices (LVADs) have been shown to increase the functional status and survival of patients with end -stage heart failure. There is limited data regarding the prevalence of arrhythmias and conduction disease in patients implanted with LVADs. Our objective was to determine the prevalence of arrhythmias and conduction disease in hospitalized patients with LVADs using the National Inpatient Sample (NIS) from 2016-2019. A retrospective study was done using the Nationwide Inpatient Sample from 2016-2019. 17,125 hospitalisations with LVADs were identified using ICD-10 codes. Multivariate logistic regression analysis was used to adjust for confounders and analyze the variables for the adjusted odds ratio. Among 17,125 hospitalizations, the average age was 55 years and 62% were male. Atrial fibrillation (AF) was the most prevalent (43%) atrial arrhythmia, followed by atrial flutter (AFL) (14%), and supraventricular tachycardia (SVT) (13%). Ventricular tachycardia (VT) was the most common ventricular arrhythmia (47%), and less than one percent of the cohort had reported episodes of ventricular fibrillation/flutter (< 1%). In terms of conduction disease, 10% had either first-degree (1AVB), <1% had second-degree AV block (2AVB), 10% had right (RBBB), and 3% had left bundle branch block (LBBB). When adjusted to patient demographics, comorbidities, and hospital characteristics, patients with LVADs had a higher risk of AF (aOR= 2.00, p<0.0001), AFL (aOR=3.5, p<0.0001), SVT (aOR=4.63, p<0.0001), VT (aOR=17.7, p<0.0001), and complete heart block (CHB) (aOR=2.6, p<0.0001). Patients with LVADs are more likely to develop atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, RBBB, and CHB. Atrial fibrillation was our cohort's most common arrhythmia, consistent with prior observational studies' trends.

Evaluation of a deep learning-enabled automated computational heart modelling workflow for personalized assessment of ventricular arrhythmias.

Personalized, image-based computational heart modelling is a powerful technology that can be used to improve patient-specific arrhythmia risk stratification and ventricular tachycardia (VT) ablation targeting. However, most state-of-the-art methods still require manual interactions by expert users. The goal of this study is to evaluate the feasibility of an automated, deep learning-based workflow for reconstructing personalized computational electrophysiological heart models to guide patient-specific treatment of VT. Contrast-enhanced computed tomography (CE-CT) images with expert ventricular myocardium segmentations were acquired from 111 patients across five cohorts from three different institutions. A deep convolutional neural network (CNN) for segmenting left ventricular myocardium from CE-CT was developed, trained and evaluated. From both CNN-based and expert segmentations in a subset of patients, personalized electrophysiological heart models were reconstructed and rapid pacing was used to induce VTs. CNN-based and expert segmentations were more concordant in the middle myocardium than in the heart's base or apex. Wavefront propagation during pacing was similar between CNN-based and original heart models. Between most sets of heart models, VT inducibility was the same, the number of induced VTs was strongly correlated, and VT circuits co-localized. Our results demonstrate that personalized computational heart models reconstructed from deep learning-based segmentations even with a small training set size can predict similar VT inducibility and circuit locations as those from expertly-derived heart models. Hence, a user-independent, automated framework for simulating arrhythmias in personalized heart models could feasibly be used in clinical settings to aid VT risk stratification and guide VT ablation therapy. KEY POINTS: Personalized electrophysiological heart modelling can aid in patient-specific ventricular tachycardia (VT) risk stratification and VT ablation targeting. Current state-of-the-art, image-based heart models for VT prediction require expert-dependent, manual interactions that may not be accessible across clinical settings. In this study, we develop an automated, deep learning-based workflow for reconstructing personalized heart models capable of simulating arrhythmias and compare its predictions with that of expert-generated heart models. The number and location of VTs was similar between heart models generated from the deep learning-based workflow and expert-generated heart models. These results demonstrate the feasibility of using an automated computational heart modelling workflow to aid in VT therapeutics and has implications for generalizing personalized computational heart technology to a broad range of clinical centres.