Recurrent Ventricular Tachyarrhythmias Research Articles

C-45 | Impact of coronary revascularization on Mortality and Ventricular Tachyarrhythmia recurrence: A Meta-Analysis

C-45 | Impact of coronary revascularization on Mortality and Ventricular Tachyarrhythmia recurrence: A Meta-Analysis

Association of ventricular tachycardia morphology induced on electrophysiology study after myocardial infarction: long-term survival and ventricular tachyarrhythmia recurrence

Abstract Background Electrophysiology study (EPS) presents a valuable risk stratification tool to facilitate the implantation of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death from ventricular tachyarrhythmia early after myocardial infarction. Purpose To investigate long-term survival of patients with inducible ventricular tachycardia (VT) at electrophysiology study (EPS) early after ST elevation myocardial infarction (MI) and possible association with site of origin of the induced VT. Methods Consecutive patients with LVEF ≤40% on day 3–5 after MI who underwent EPS were prospectively recruited. Positive EPS was defined as sustained monomorphic VT cycle length ≥200ms for >10 seconds, or shorter duration if hemodynamic compromise occurred. The primary outcome was time to death from any cause. The secondary outcome was time to the composite endpoint of first activation of ICD for ventricular tachyarrhythmia or death. Results A total of 126 patients with inducible VT on EPS early after MI were included with median follow up 6.7 years. 54% had LBBB and 46% had RBBB morphologies during induced VT. The distributions of age, sex, left ventricle ejection fraction, cardiovascular risk factors, infarct artery and EPS characteristics did not differ significantly by induced VT morphology. The estimated risk of death was independently associated with RBBB morphology of VT induced at EPS (adjusted HR 3.2, 95%CI 1.0-10.0, p=0.044). The estimated risk of the composite end-point of spontaneous ventricular tachyarrhythmia recurrence or death was also independently associated with RBBB morphology of VT induced at EPS (HR 1.8, 95%CI 1.0-3.2, p=0.043). Conclusion There is an increased risk of death and spontaneous ventricular tachyarrhythmia recurrence at median follow up of 6.7 years, associated with RBBB morphology of VT (likely origin from left ventricle) induced at EPS early after MI, in those with LVEF <40%. This study is the first to characterise the association between site of origin of VT induced at EPS after myocardial infarction, indicated by RBBB or LBBB morphology, and overall survival as well as activation free survival. The results could help to identify a group of patients that could benefit from closer monitoring post MI and more intense preventative management to improve long-term outcomes.

Optimizing electrophysiology studies to prevent sudden cardiac death after myocardial infarction.

This study assessed associations of minimum final extrastimulus coupling interval utilized within electrophysiology study (EPS) after myocardial infarction (MI) and possible site of origin of induced ventricular tachycardia (VT) with long-term occurrence of spontaneous ventricular tachyarrhythmia and long-term survival. This prospective study recruited consecutive patients with left ventricular ejection fraction (LVEF) ≤ 40% who underwent EPS days 3-5 after MI between 2004 and 2017. Positive EPS was defined as sustained monomorphic VT cycle length ≥200 ms for ≥10 s or shorter duration if haemodynamic compromise occurred. Each of the four extrastimuli was shortened by 10 ms at a time, until it failed to capture the ventricle (ventricular refractoriness) or induced ventricular tachyarrhythmia. Outcomes included spontaneous ventricular tachyarrhythmia occurrence and all-cause mortality. Shorter coupling interval length of final extrastimulus that induced VT was associated with higher risk of spontaneous ventricular tachyarrhythmia (P < 0.001). Significantly higher rates of spontaneous ventricular tachyarrhythmia (65.2% vs. 23.2%; P < 0.001) were observed for final coupling interval at EPS <200 ms vs. >200 ms. Right bundle branch block (RBBB) morphology of induced VT, with possible site of origin from the left ventricle, was associated with all-cause mortality [hazard ratio (HR) 3.2, P = 0.044] and a composite of spontaneous ventricular tachyarrhythmia recurrence or mortality (HR 1.8, P = 0.043). Ventricular tachycardia induced with shorter coupling intervals was associated with higher risk of spontaneous ventricular tachyarrhythymia on follow-up, indicating that the final extrastimulus coupling interval at EPS early after MI should be determined by ventricular refractoriness. Induced VT with possible origin from left ventricle was associated with increased risk of spontaneous ventricular tachyarrhythmia recurrence or death.

The Arrhythmogenicity of Sotalol and its Role in Heart Failure: A Literature Review.

According to the American Heart Association (AHA), approximately six million adults have been afflicted with heart failure (HF) in the United States in 2020 and are more likely to have sudden cardiac death accounting for approximately 50% of the cause of mortality. Sotalol is a nonselective β-adrenergic receptor antagonist with class III antiarrhythmic properties that has been mostly utilized for atrial fibrillation treatment and suppressing recurrent ventricular tachyarrhythmias. The use of sotalol in patients with left ventricular (LV) dysfunction is not recommended by the American College of Cardiology (ACC) or AHA as studies are inconclusive with conflicting results regarding safety. This article aims to review the mechanism of action of sotalol, the β-blocking effects on heart failure, and provide an overview of clinical trials on sotalol use and its effects in patients with heart failure. Small and large scale clinical trials have been controversial and inconclusive about the use of sotalol in heart failure. Sotalol has been shown to reduce defibrillation energy requirements and reduce shocks from implantable cardioverter-defibrillators. TdP is the most life-threatening arrhythmia that has been documented with sotalol use and occurs more commonly in women and HF patients. Thus far, mortality benefits have not been demonstrated with sotalol use and larger multicenter studies are required going forward.

PO-04-226 RISK OF VENTRICULAR RECURRENT TACHYARRHYTHMIA IN PATIENTS RECEIVING PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

Implantable cardioverter-defibrillators (ICDs) have demonstrated efficacy in reducing mortality attributable to sustained ventricular tachyarrhythmia (VTA) and have been used for primary prevention of sudden death. However, patients with primary prevention ICDs remain at risk for first and recurrent VTA, which are associated with increased morbidity and mortality. Currently, there are limited data on factors associated with recurrent VTA after the occurrence of a first episode in this population. Improved risk stratification may help tailor advanced therapies, such as catheter ablation or antiarrhythmic medications, to patients at a high risk for recurrence. The objective of this study was to quantify the risk for recurrent VTA after the occurrence of a first VTA episode among patients with a primary prevention ICD. The population comprised patients enrolled in five landmark ICD trials (MADIT-II, MADIT-Risk, MADIT-CRT, MADIT-RIT, RAID) who experienced a first episode of VTA (defined as ventricular tachycardia [VT] ≥170 bpm or ventricular fibrillation [VF]) after ICD implantation (N=789). The primary endpoint was recurrent VTA after a first episode. All-cause mortality associated with recurrent VTA was a secondary endpoint. Among 789 study patients who experienced a first VTA after ICD implantation, mean age was 63 ± 11 years, 17% were women, 64% had ischemic cardiomyopathy, and mean left ventricular ejection fraction (EF) was 24 ± 7%. Kaplan Meier analysis showed the risk of recurrent VTA after a first episode was very high (60% at 3 years [Figure - A]). Findings were consistent regardless of baseline risk factors, including age, sex, NYHA Class, EF. Furthermore, the burden of multiple VTA episodes after a first episode was also high (average of 3.6 episodes per patient at 3 years [Figure B]). Recurrent VTA was associated with a significant two-fold increased risk of subsequent death (HR=2.15, 95% CI 1.40-3.32, p=0.001 [Figure - C]). Among primary prevention ICD recipients who experience a first VTA, the burden of recurrent VTA and subsequent mortality increase is very high regardless of baseline risk factors. Intensification of therapies, including early catheter ablation, should be considered in primary prevention ICD recipients who experience a first VTA.

РЕПЕРФУЗИОННЫЙ СИНДРОМ ПРИ ЭНДОВАСКУЛЯРНОЙ РЕВАСКУЛЯРИЗАЦИИ МИОКАРДА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

CHD retains a leading position worldwide due to high rates of mortality and disability. The best and proven strategy aimed at saving the damaged myocardium in ST-segment elevation myocardial infarction (STEMI) is rapid and effective reperfusion of the ischemic heart muscle through primary percutaneous coronary intervention (PCI) or pharmacoinvasive therapy. However, the restoration of blood flow by itself can lead to reperfusion damage to the affected myocardium. In acute coronary catastrophe caused by acute occlusion of the coronary artery, myocardial stun and hibernation develop locally. With STEMI, hibernation can be observed both near the infarction zone and in more distant areas of the myocardium. In patients with STEMI, the appearance of life-threatening arrhythmias (ventricular tachycardia and ventricular fibrillation) occurs in 4.3 % of cases and is primarily associated with reperfusion after PCI. In most cases, arrhythmias that occur during the procedure are stopped spontaneously; however, when accompanied by ventricular tachyarrhythmia, hemodynamic instability, the use of electric pulse therapy (EIT) is provided. The article presents a clinical case of a patient C., 52, whose reperfusion syndrome manifested itself by the development of life-threatening ventricular tachyarrhythmias: unstable ventricular tachycardia «torsade de points» with transformation into VF, which were stopped by EIT: defibrillation. No recurrence of ventricular tachyarrhythmia was observed in this patient. At this stage, we explain the resulting episode of unstable ventricular tachycardia with short-term myocardial stunning due to short-term ischemia and myocardial damage.

A Soccer Shot with Lengthy Consequences—Case Report &amp; Current Literature Review of Commotio Cordis

(1) Background: Commotio cordis, caused by objects being directly delivered to the chest, may cause cardiac arrest in young athletes, even without identifiable structural damage to the sternum, ribs or heart itself. Its prevention and management often remain suboptimal, resulting in dismal outcomes. (2) Case summary: A 32-year semi-professional goalkeeper suffered from a non-penetrating blunt thoracic trauma after being struck by a high-velocity shot during a regional league soccer game. He immediately lost consciousness, collapsed, and was successfully resuscitated through early defibrillation of ventricular fibrillation. After an uneventful follow-up for approximately 6 years, recurrent episodes of ventricular tachycardia occurred, which could ultimately only be prevented by epicardial ablation. (3) Conclusion: Very late recurrences of ventricular tachyarrhythmias may occur after ventricular fibrillation due to blunt chest trauma, even in the primary absence of evident structural myocardial damage.

High-resolution structural-functional substrate-trigger characterization: Future roadmap for catheter ablation of ventricular tachycardia.

Patients with ventricular tachyarrhythmias (VT) are at high risk of sudden cardiac death. When appropriate, catheter ablation is modestly effective, with relatively high VT recurrence and complication rates. Personalized models that incorporate imaging and computational approaches have advanced VT management. However, 3D patient-specific functional electrical information is typically not considered. We hypothesize that incorporating non-invasive 3D electrical and structural characterization in a patient-specific model improves VT-substrate recognition and ablation targeting. In a 53-year-old male with ischemic cardiomyopathy and recurrent monomorphic VT, we built a structural-functional model based on high-resolution 3D late-gadolinium enhancement (LGE) cardiac magnetic resonance imaging (3D-LGE CMR), multi-detector computed tomography (CT), and electrocardiographic imaging (ECGI). Invasive data from high-density contact and pace mapping obtained during endocardial VT-substrate modification were also incorporated. The integrated 3D electro-anatomic model was analyzed off-line. Merging the invasive voltage maps and 3D-LGE CMR endocardial geometry led to a mean Euclidean node-to-node distance of 5 ± 2 mm. Inferolateral and apical areas of low bipolar voltage (<1.5 mV) were associated with high 3D-LGE CMR signal intensity (>0.4) and with higher transmurality of fibrosis. Areas of functional conduction delay or block (evoked delayed potentials, EDPs) were in close proximity to 3D-LGE CMR-derived heterogeneous tissue corridors. ECGI pinpointed the epicardial VT exit at ∼10 mm from the endocardial site of origin, both juxtaposed to the distal ends of two heterogeneous tissue corridors in the inferobasal left ventricle. Radiofrequency ablation at the entrances of these corridors, eliminating all EDPs, and at the VT site of origin rendered the patient non-inducible and arrhythmia-free until the present day (20 months follow-up). Off-line analysis in our model uncovered dynamic electrical instability of the LV inferolateral heterogeneous scar region which set the stage for an evolving VT circuit. We developed a personalized 3D model that integrates high-resolution structural and electrical information and allows the investigation of their dynamic interaction during arrhythmia formation. This model enhances our mechanistic understanding of scar-related VT and provides an advanced, non-invasive roadmap for catheter ablation.

Impact of age on the prognosis of patients with ventricular tachyarrhythmias and aborted cardiac arrest.

This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest. The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60years old) were compared to older patients (> 60years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment. Atotal of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as acontinuous variable was independently associated with mortality at 2.5years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis. The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5years and the secondary endpoints.

Carvedilol versus Metoprolol in Patients with Ventricular Tachyarrhythmias.

The study investigates the prognostic role of treatment with carvedilol as compared to metoprolol in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients on beta-blocker (BB) treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with carvedilol were compared to patients with metoprolol. The primary prognostic outcome was all-cause mortality at three years. Secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies) and cardiac rehospitalization. Kaplan–Meier survival curves, multivariable Cox regression analyses, and propensity score matching were applied for statistics. There were 1098 patients included, 80% treated with metoprolol and 20% with carvedilol. Patients with carvedilol were older, more often presenting with VT (78% vs. 62%; p = 0.001) and with more advanced stages of heart failure. Treatment with carvedilol was associated with comparable all-cause mortality compared to metoprolol (20% vs. 16%, log rank p = 0.234; HR = 1.229; 95% CI 0.874–1.728; p = 0.235). However, secondary endpoints (i.e., composite arrhythmic endpoint: 32% vs. 17%; p = 0.001 and cardiac rehospitalization: 25% vs. 14%; p = 0.001) were more frequently observed in patients with carvedilol, which was still evident after multivariable adjustment. After propensity score matching (n = 194 patients with carvedilol and metoprolol), no further differences regarding the distribution of baseline characteristics were observed. Within the propensity-score-matched cohort, higher rates of the composite arrhythmic endpoint were still observed in patients treated with carvedilol, whereas the risk of cardiac rehospitalization was not affected by the type of beta-blocker treatment. In conclusion, carvedilol and metoprolol are associated with comparable all-cause mortality in patients with ventricular tachyarrhythmias, whereas the risk of the composite arrhythmic endpoint was increased in patients with carvedilol therapy.

Digitalis therapy in patients with ventricular tachyarrhythmias

Objective. The study sought to assess the prognostic value of treatment with digitalis on long-term prognosis in patients with ventricular tachyarrhythmias and atrial fibrillation (AF) and/or heart failure (HF). Background. Data regarding the outcome of digitalis therapy following ventricular tachyarrhythmias is limited. Methods. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with digitalis were compared to patients without. The primary prognostic endpoint was all-cause mortality at 3 years, secondary endpoints comprised a composite arrhythmic endpoint (i.e. recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies, sudden cardiac death) and cardiac rehospitalization. Kaplan Mayer survival curves, multivariable cox regression, and time trend analyses were applied for statistics. Results. Eight hundred and thirty-one patients were included (20% treated with digitalis and 80% without). At 3 years, digitalis treatment was not associated with all-cause mortality following ventricular tachyarrhythmias (24 vs. 21%, log-rank p = .736; HR = 1.063; 95% CI 0.746–1.515; p = .736). However, digitalis therapy was associated with an increased risk of the composite arrhythmic endpoint (38 vs. 23%; log-rank p = .001; HR = 1.719; 95% CI 1.279–2.311; p = .001) and cardiac rehospitalization (31 vs. 18%; log-rank p = .001; HR = 1.829; 95% CI 1.318–2.538; p = .001), which was still evident within multivariable Cox regression analyses. Finally, digitoxin may be associated with a worse prognosis than digoxin. Conclusion. Digitalis therapy was not associated with mortality in patients with ventricular tachyarrhythmias, but with increased risk of the composite arrhythmic endpoint and cardiac rehospitalization at 3 years.

Predictors of long-term ventricular tachyarrhythmia recurrence after combined endo-epicardial ablation in patients with structural heart disease

Purpose. To identify predictors of ventricular tachycardia (VT) recurrence after endo-epicardial ablation in patients with structural heart disease.Methods. A prospective observational study included 39 patients with structural heart disease and indications for catheter ablation of ventricular tachyarrhythmia. Endo- and epicardial electroanatomical mapping of the ventricular myocardium and ablation of abnormal electrical activity areas were performed. Clinical, ECG characteristics, and voltage maps of bipolar potentials (limits of scar detection &lt;0.5 mV, normal activity &gt;1.5 mV) and unipolar signals (limits &lt;5.0 and &gt;9.0 mV, respectively) on endo- and epicardial surfaces were evaluated. Intraprocedurally, the procedure was considered effective when no VT was inducible; partially effective - when only clinical VT(s) was/were non-inducible. Scheduled patient visits or remote monitoring were performed at 6, 12 and 24 months, and then annually.Results. The mean age of the patients was 49.5±15.7 years (34 men and 5 women). VT recurrences at 6 months were more often detected in non-ischemic cardiomyopathy patients, in subjects with non-paroxysmal atrial fibrillation (42.9% vs. 7.4%), with a lower VT-QRS amplitude in lead III (0.6 [0.4;1.07] versus 1.28 [0.99; 1.53] mV), and when epicardial “scar” area prevailed over endocardial, P&lt;0.05 for all listed parameters. At 12-months, VT recurrence was more common in patients with partially effective ablation (33.3% vs. 5.0% in patients with effective ablation, P=0.02). The presence of electrical storm at the time of ablation was independently associated with recurrences (HR 4.32; 95% CI: 1.06-17.48; P=0.04).Conclusion. In a heterogeneous group of patients, clinical and electrophysiological factors associated with VT recurrence have been identified at various follow-up periods after endo-epicardial ablation. Electrical storm ablation is an independent predictor of VT recurrence in the long-term, up to 5 years of follow-up.

Sex Differences in the Risk of First and Recurrent Ventricular Tachyarrhythmias Among Patients Receiving an Implantable Cardioverter-Defibrillator for Primary Prevention

Current guidelines for primary implantable cardioverter-defibrillator (ICD) therapy do not account for sex differences in arrhythmic risk in ICD candidates. To evaluate the association between sex and risk of ventricular tachyarrhythmia (VTA) and mortality. This cohort study compared differences in the risk of VTA and mortality between 4506 men and women enrolled in the 4 Multicenter Automatic Defibrillator Implantation Trials (MADIT) between July 1, 1997, and December 31, 2011. Data from prospective randomized controlled multicenter studies were analyzed retrospectively. Men and women with an ICD or cardiac resynchronization therapy defibrillator who were enrolled in all MADIT studies were included. Data were analyzed between January 10 and June 10, 2021. ICD implant. The primary end point was sustained VTA, defined as ICD-recorded, treated or monitored VTA at least 170/min or ventricular fibrillation. Secondary VTA end points included VTA at least 200/min, appropriate ICD shocks, and appropriate antitachycardia pacing. All end points were included in a first and recurrent event analysis. Of the 4506 study participants, 3431 were men (76%). Mean (SD) age of the cohort was 64 (12) years. For women vs men, the mean (SD) age (64 [12] years vs 64 [11] years) and left ventricular ejection fraction (24% vs 25%) were similar, but women exhibited a higher frequency of nonischemic cardiomyopathy (454 of 1075 women [42%] vs 2535 of 3431 men [74%]). Women had significantly lower 3-year cumulative probability of sustained VTA (16% vs 26%), fast VTA (9% vs 17%), and appropriate ICD shocks (7% vs 15%) compared with men (P < .001 for all). Multivariable analysis showed that female sex was independently associated with at least 40% lower risk of all first and recurrent VTA end points (P < .001 for all), including the primary end point (first event, HR = 60 [95% CI, 50-73], P < .001; recurrent event, HR = 49 [95% CI, 43-55], P < .001), after accounting for the competing risk of all-cause mortality and nonarrhythmic mortality. The lower VTA risk associated with female sex was consistent in risk subsets but was significantly more pronounced in patients with nonischemic cardiomyopathy (female vs male in the ischemic group: hazard ratio, 0.73 [95% CI, 0.56-0.95], P = .02; nonischemic group: hazard ratio, 0.50 [95% CI, 0.38-0.66], P < .001; P = .03 for interaction between female sex and cardiomyopathy). Findings suggest that women display a significantly lower risk of first and recurrent life-threatening VTA events than men, and that it is more pronounced in patients with nonischemic cardiomyopathy, suggesting a need for sex-specific risk assessment for primary prevention ICD therapy.

Reduction in Ventricular Tachyarrhythmia Burden in Patients Enrolled in the RAIDTrial.

The RAID (Ranolazine Implantable Cardioverter-Defibrillator) randomized placebo-controlled trial showed that ranolazine treatment was associated with reduction in recurrent ventricular tachycardia (VT) requiring appropriate implantable cardioverter-defibrillator (ICD) therapy. This study aimed to identify groups of patients in whom ranolazine treatment would result in the highest reduction of ventricular tachyarrhythmia (VTA) burden. Andersen-Gill analyses were performed to identify variables associated with risk for VTA burden among 1,012 patients enrolled in RAID. The primary endpoint was VTA burden defined as VTA episodes requiring appropriate treatment. Multivariate analysis identified 7 factors associated with increased VTA burden: history of VTA, age≥65 years, New York Heart Association functional class≥III, QRS complex (≥130ms), low ejection fraction (<30%), atrial fibrillation (AF), and concomitant antiarrhythmic drug (AAD) therapy. The effect of ranolazine on VTA burden was seen among patients without concomitant AAD therapy (HR [HR]: 0.68; 95%CI: 0.55-0.84; P< 0.001), whereas no effect was seen among those who are concomitantly treated with other AADs (HR: 1.33; 95%CI: 0.90-1.96; P = 0.16); P = 0.003 for interaction. In patients with cardiac resynchronization therapy (CRT) ICDs, ranolazine treatment was associated with a 36% risk reduction for VTA recurrence (HR: 0.64; 95%CI: 0.47-0.86; P< 0.001), whereas among patients with ICDs without CRT no significant effect was noted (HR: 0.94; 95%CI: 0.74-1.18; P = 0.57); P = 0.047 for interaction. In patients with high risk for VTA, ranolazine is effective in reducing VTA burden, with significantly greater effect in CRT-treated patients, those without AF, and those not treated with concomitant AADs. In patients already on AADs or those with AF, the addition of ranolazine did not affect VTA burden. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

Comparison between oral procainamide and mexiletine for the treatment of recurrent and refractory ventricular tachyarrhythmias

Abstract Funding Acknowledgements Type of funding sources: None. Background The antiarrhythmic therapy of recurrent ventricular arrhythmias in patients having undergone catheter ablation and in whom amiodarone and/or beta blockers were ineffective or contraindicated, is a controversial issue. Purpose The present study sought to compare the efficacy and tolerability of oral procainamide and mexiletine in patients with recurrent ventricular arrhythmias, when the standard therapy strategy failed. Methods All patients with an implantable cardioverter defibrillator (ICD) treated with oral procainamide or mexiletine for recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) in 2 Cardiology Divisions between January 2010 and January 2020 were enrolled. The patients were divided in group A (oral procainamide) and group B (mexiletine) and the 2 groups were compared to each other. The primary endpoint was the efficacy of therapy; the secondary endpoint was the discontinuation of therapy. All the events occurring during procainamide or mexiletine treatment were compared with a matched duration period before the initiation of the therapy. Antiarrhythmic therapy was considered effective when an ≥80% reduction of the sustained ventricular arrhythmias (SVA) burden recorded by the ICD was achieved. Results A total of 68 consecutive patients (61 males, 89.7%; mean age 74 ± 10 years) were included in this retrospective analysis. In 27 (39.7%) patients catheter ablation of VT was attempted before therapy initiation. A concomitant therapy with amiodarone was present in 25 (36.8%) patients. The mean dose of procainamide was 1207±487 mg/die. The mean dose of mexiletine was 576±66 mg/die. After a median follow-up of 19 months, 38 (56%) patients had a significant reduction in the SVA burden. After multivariable adjustment (Table 1), therapy with procainamide was independently associated with an almost 3-fold higher efficacy on VA suppression compared to mexiletine (HR 2.54, 95% CI 1.06-6.14, p=0.03). Similar results (HR 2.89, 95% CI 1.26-6.62, p=0.01) were found after adjustment using inverse probability weighting by a propensity score including age, gender, left ventricular ejection fraction, ischemic heart disease and concomitant amiodarone therapy. Only 3 patients (9%) treated with procainamide presented severe side effects (dyspnea or hypotension) requiring discontinuation of therapy against 6 patients (18%) treated with mexiletine who interrupted therapy because of severe side effects (p=0.47). Conclusions Compared to mexiletine, oral procainamide has a higher efficacy for the treatment of recurrent and refractory VAs and shows a good profile of tolerability Table 1. Multivariable Cox Proportional Hazards Analysis of Baseline Covariates in Relation to effective VAs suppression.

Biological substrate modification suppresses ventricular arrhythmias in a porcine model of chronic ischaemic cardiomyopathy.

Cardiomyopathy patients are prone to ventricular arrhythmias (VA) and sudden cardiac death. Current therapies to prevent VA include radiofrequency ablation to destroy slowly conducting pathways of viable myocardium which support re-entry. Here, we tested the reverse concept, namely that boosting local tissue viability in zones of slow conduction might eliminate slow conduction and suppress VA in ischaemic cardiomyopathy. Exosomes are extracellular vesicles laden with bioactive cargo. Exosomes secreted by cardiosphere-derived cells (CDCEXO) reduce scar and improve heart function after intramyocardial delivery. In a VA-prone porcine model of ischaemic cardiomyopathy, we injected CDCEXO or vehicle into zones of delayed conduction defined by electroanatomic mapping. Up to 1-month post-injection, CDCEXO, but not the vehicle, decreased myocardial scar, suppressed slowly conducting electrical pathways, and inhibited VA induction by programmed electrical stimulation. In silico reconstruction of electrical activity based on magnetic resonance images accurately reproduced the suppression of VA inducibility by CDCEXO. Strong anti-fibrotic effects of CDCEXO, evident histologically and by proteomic analysis from pig hearts, were confirmed in a co-culture assay of cardiomyocytes and fibroblasts. Biological substrate modification by exosome injection may be worth developing as a non-destructive alternative to conventional ablation for the prevention of recurrent ventricular tachyarrhythmias.

Angiotensin Converting Enzyme Inhibitors versus Receptor Blockers in Patients with Ventricular Tachyarrhythmias.

Data investigating the prognostic value of treatment with angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB) usually focusses on patients presenting with heart failure (HF) or acute myocardial infarction (AMI). However, by preventing adverse cardiac remodeling, ACEi/ARB may also decrease the risk of ventricular tachyarrhythmias and sudden cardiac death (SCD). Although ventricular tachyarrhythmias are associated with significant mortality and morbidity, only limited data are available focusing on the prognostic role of ACEi/ARB, when prescribed for secondary prevention of SCD. Therefore, this study comprehensively investigates the role of ACEi versus ARB in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. The primary prognostic outcome was all-cause mortality at three years, secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, ICD therapies and sudden cardiac death) and cardiac rehospitalization. A total of 1236 patients were included (15% treated with ARB and 85% with ACEi) and followed for a median of 4.0 years. At three years, ACEi and ARB were associated with comparable long-term mortality (20% vs. 17%; log rank p = 0.287; HR = 0.965; 95% CI 0.689–1.351; p = 0.835) and comparable risk of the composite arrhythmic endpoint (HR = 1.227; 95% CI 0.841–1.790; p = 0.288). In contrast, ACEi was associated with a decreased risk of cardiac rehospitalization at three years (HR = 0.690; 95% CI 0.490–0.971; p = 0.033). Within the propensity score matched cohort (i.e., 158 patients with ACEi and ARB), ACEi and ARB were associated with comparable long-term outcomes at three years. In conclusion, ACEi and ARB are associated with comparable risk of long-term outcomes in patients presenting with ventricular tachyarrhythmias.

Distribution and prognostic impact of coronary artery disease and nonischemic cardiomyopathies in patients with electrical storm.

he distribution and prognostic impact of coronary artery disease (CAD) in ES are still under debate. Consecutive ES patients with implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Three analyses were applied to characterize ES patients: (a) ES patients without CAD (non-CAD), (b) ES patients with CAD (CAD), and (c) diagnostic findings assessed by coronary angiography (CA) at the time of ES (immediate CA). CAD was compared with non-CAD ES patients, and progressive CAD was compared with stable CAD ES patients. The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were the composite endpoint of first recurrent ventricular tachyarrhythmias and appropriate ICD therapies, and recurrence of ES (ES-R) at 2.5 years. Within a total of 87 consecutive ES patients. CAD was present in more than two-thirds (67%). However, only 52% patients underwent immediate CA at the time of ES. Here, 84% had CAD, of which 39% revealed progressive CAD with the need of target vessel revascularization (TVR) or cardiac transplantation ( n = 1). At long-term follow-up, neither the presence (or absence) of CAD (41% vs. 34%; log rank P = 0.708) nor of progressive CAD (33% vs. 26%; log rank P = 0.372) was associated with all-cause mortality at 2.5 years, and further secondary endpoints including the composite of recurrent ventricular tachyarrhythmias plus appropriate ICD therapies, or ES-R. In ES patients, CAD was more common than non-CAD-related cardiac diseases, accompanied by an underinvestigated rate of CA despite increasing rates of progressive CAD. CAD had no prognostic impact in ES.

Prognostic value of beta-blocker doses in patients with ventricular tachyarrhythmias

The study investigates the prognostic significance of beta-blocker (BB) dose in patients with ventricular tachyarrhythmias. Limited data regarding the prognostic impact of BB dose in ventricular tachyarrhythmias is available. A large retrospective registry was used including consecutive patients on BB treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Discharge BB doses were grouped as > 0–12.5%, > 12.5–25%, > 25–50%, and > 50% according to doses used in randomized trials. The primary endpoint was all-cause mortality at three years. Secondary endpoints comprised of a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias and appropriate ICD therapies) and cardiac rehospitalization. Kaplan–Meier survival curves and multivariable Cox regression analyses were applied for statistics. A total of 1313 patients with BB were included; most patients were discharged with > 25–50% of BB target dose (59%). At three years, > 12.5–25% of BB target dose was associated with improved long-term mortality as compared to the > 0–12.5% group (HR = 0.489; 95% CI 0.297–0.806; p = 0.005), whereas higher BB doses did not improve survival (> 25–50%: HR = 0.849; p = 0.434; > 50%: HR = 0.735; p = 0.285). In contrast, the composite endpoint and risk of rehospitalization were not affected by BB target dose. In conclusion, > 12.5–25% of BB target dose is associated with best long-term survival among patients with ventricular tachyarrhythmias. In contrast, risk of the composite arrhythmic endpoint and risk of cardiac rehospitalization were not affected by BB dose.

Effect of Mineralocorticoid Receptor Antagonists on the Prognosis of Patients with Ventricular Tachyarrhythmias

Introduction: The study sought to assess the effect of treatment with mineralocorticoid receptor antagonists (MRAs) on long-term prognosis of patients with systolic heart failure (HF) surviving index episodes of ventricular tachyarrhythmias. Methods: A large retrospective registry was used including consecutive HF patients with left ventricular ejection fraction <45% and index episodes of ventricular tachyarrhythmias from 2002 to 2015. The primary endpoint was all-cause mortality at 3 years and secondary endpoints were rehospitalization, as well as the composite endpoint consisting of recurrent ventricular tachyarrhythmias, sudden cardiac death and appropriate implantabe cardioverter defibrillator (ICD) therapies at 3 years. Results: 748 patients were included, 20% treated with MRA and 80% without. At 3 years, treatment with MRA was not associated with improved all-cause mortality (22% vs. 24%, log-rank p = 0.968; hazard ratio (HR) = 1.008; 95% CI 0.690–1.472; p = 0.968). Accordingly, risk of the composite endpoint (28% vs. 27%; HR = 1.131; 95% CI 0.806–1.589; p = 0.476) and first cardiac rehospitalization (24% vs. 22%; HR = 1.139; 95% CI 0.788–1.648; p = 0.489) were not affected by treatment with MRA. Conclusion: In patients with ventricular tachyarrhythmias, treatment with MRA was not associated with improved all-cause mortality at 3 years. The therapeutic effect of MRA treatment in patients with ventricular tachyarrhythmias needs to be reinvestigated within further randomized controlled trials.