Rate Of Ventricular Arrhythmias Research Articles

Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Sex differences in hospitalization for ventricular arrhythmia after a first myocardial infarction in patients without indication for implantable cardioverter-defibrillator implantation

Abstract Background Ventricular arrhythmias (VAs) represent a serious complication of myocardial infarction (MI). Incidence rate of VAs and sudden cardiac death is commonly reported to be lower in women than in men after MI (1,2). While data regarding SCD and VAs after MI in patients with implantable cardioverter defibrillator (ICD) are well described, data regarding the incidence of readmissions for VA in patients without ICD implantation criteria after a first MI are scarce, as well as the impact of sex on their occurrence. Objective This study aims to investigate the impact of sex on VA occurrences in post-MI patients without ICD implantation criteria. Methods This study was conducted using the French national health data system using electronic codes for procedures (CCAM) and hospitalizations data (PMSI). The study population consisted of patients discharged after a first MI and without criteria for ICD implantation. Results Between January 2014 and January 2015, 137,736 patients were hospitalized in France with a diagnosis of first MI and were followed using CCAM and PMSI codes. Among the 112,465 alive at discharge, 6838 patients were excluded due to criteria for the implantation of an ICD for primary or secondary prevention. Of the remaining 105,629 patients, 1600 (1.51%) were rehospitalized for VA with a median delay of 505 days (IQR 110-1208). Men had almost twice the risk of VA than women after initial discharge for MI (OR 1.88, 95% CI 1.65-2.14; p<0.0001). Among the 72,103 men included, 1240 (1.72%) were rehospitalized for VA with a median delay of 514 days (IQR 107-1212). Factors independently associated with VA in men were previous atrial fibrillation (OR 1.91, 95% CI 1.66 - 2.21, p<0.0001), previous vascular disease (OR 1.28, 95% CI 1.10 - 1.50, p=0.002), absence of coronary angioplasty (OR 1.28, 95% CI 1.10 - 1.50, p=0.002), previous diabetes (OR 1.19, 95% CI 1.04 - 1.36, p=0.012), previous hypertension (OR 1.19, 95% CI 1.05 - 1.34, p=0.007), previous or in-hospital congestive heart failure (OR 1.47, 95% CI 1.03-2.08, p=0.032 and OR 1.65, 95% CI 1.32-2.07, p<0.0001), and age (patients between 60 and 79 yo being at the higher risk of VA compared to <60 and >80yo patients, p=0.002 and <0.0001 respectively). Among the 33,526 women included, 360 (1.07%) were rehospitalized for VA with a median (IQR) delay of 461 days (116-1159) after MI. Factors independently associated with VA were previous atrial fibrillation (OR 1.68, 95% CI 1.30 - 2.18, p<0.0001), previous vascular disease (OR 1.37, 95% CI 1.01 - 1.84, p=0.041), and age (patients between 60 and 79 yo being at the higher risk of VA compared to >80yo patients, p=0.001). Conclusion The risk of readmission for VAs after a first MI is significantly lower in women compared to men, with distinct predictive factors. These findings suggest that sex-specific VA risk stratification and management strategies may be warranted after an initial MI.Sexe influence on post-MI VAs occurence

Risk profiles for ventricular arrhythmias in hypertrophic cardiomyopathy through clustering analysis including left ventricular strain.

AimsThe prediction of ventricular arrhythmia (VA) in hypertrophic cardiomyopathy (HCM) remains challenging. We sought to characterize the VA risk profile in HCM patients through clustering analysis combining clinical and conventional imaging parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). MethodsA total of 434 HCM patients (65% men, mean age 56 years) were included from two referral centers and followed longitudinally (mean duration 6 years). Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The principal endpoint was VA. Results4 clusters were identified with a higher rhythmic risk for clusters 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively). These 4 clusters differed mainly by LV-mechanics with a severe and homogeneous decrease of myocardial deformation for cluster 4, a small decrease for clusters 2 and 3 and a marked deformation delay and temporal dispersion for cluster 1 associated with a moderate decrease of the GLS (p < 0.0001 for GLS comparison between clusters). Patients from cluster 4 had the most severe phenotype (mean LV mass index 123 vs. 112 g/m2; p = 0.0003) with LV and left atrium (LA) remodeling (LA-volume index (LAVI) 46.6 vs. 41.5 ml/m2, p = 0.04 and LVEF 59.7 vs. 66.3%, p < 0.001) and impaired exercise capacity (% predicted peak VO2 58.6 vs. 69.5%; p = 0.025). ConclusionProcessing LV-LS parameters in HCM patients 4 clusters with specific LV-strain patterns and different rhythmic risk levels are identified. Automatic extraction and analysis of LV strain parameters improves the risk stratification for VA in HCM patients.

Long-term Rate of Ventricular Arrhythmia in Autoimmune Disease.

Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of our study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs. Individuals diagnosed with an AID (2005-2018) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. In total, 186,733 patients diagnosed with AIDs were matched with 746,932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals (HR 1.39 [95% CI, 1.29-1.49]). The highest HR was observed in patients with systemic sclerosis (3.86 [95% CI, 1.92-7.75]). The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischemic heart disease or heart failure/cardiomyopathy compared to those with these conditions (Pinteraction < 0.05). Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.

Analysis of Ventricular Arrhythmias and Sudden Death with Acalabrutinib from 5 Prospective Clinical Trials

Background: The approval of ibrutinib, the first covalent Bruton tyrosine kinase inhibitor (BTKi), provided an effective non-chemotherapy option for the treatment of B-cell malignancies, such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). While generally well tolerated, ibrutinib demonstrated significant toxicities in clinical studies, particularly cardiovascular adverse events such as hypertension, atrial fibrillation, and ventricular arrhythmias (VAs). Post hoc analysis of the phase 3 FLAIR trial in patients with previously untreated CLL reported an unexplained sudden or cardiac death rate of 0.5 patients per 100 patient-years with ibrutinib plus rituximab (Hillmen et al. Lancet Oncol. 2023). Acalabrutinib is a next-generation, more selective, irreversible BTKi approved to treat CLL/SLL and relapsed/refractory mantle cell lymphoma. Herein, the rates of nonfatal and fatal VAs and sudden deaths (SDs) from 5 acalabrutinib clinical trials of patients with CLL were analyzed. Methods: Incidence and relative risk of nonfatal and fatal VAs and SDs were analyzed using pooled data from 5 prospective acalabrutinib clinical trials (nonrandomized trials: CL-001 [acalabrutinib monotherapy], CL-003 [acalabrutinib + obinutuzumab]; randomized trials: CL-006 [acalabrutinib vs ibrutinib], CL-007 [acalabrutinib ± obinutuzumab vs chlorambucil + obinutuzumab], CL-309 [acalabrutinib vs idelalisib + rituximab OR bendamustine + rituximab]). Acalabrutinib-containing arms were pooled as a single group; comparators, which were standard-of-care therapies, were pooled as a separate group. Events were identified by comprehensive data extraction of terms capturing nonfatal and fatal VAs and SDs (terms are defined in Table 1 footnote). Nonfatal events were analyzed with and without the inclusion of premature ventricular contractions (PVCs). A subset of fatal events also was analyzed after adjudication through manual clinical review by the sponsor's medical, clinical, and safety leadership. Results: In total, 1299 patients received acalabrutinib (cumulative exposure, 4568.4 patient-years) and 585 received standard-of-care therapies (comparator group) (941.3 patient-years). Considering only fatal VAs and SDs, 5 (0.4%) and 3 (0.5%) patients had an event in the acalabrutinib and comparator groups, respectively, via comprehensive data extraction ( Table 1). Based on exposure-adjusted event rates per 100 patient-years, fatal VAs and SDs were numerically less frequent for acalabrutinib versus comparators; however, relative risks did not statistically favor either group. This trend persisted when events were adjudicated through manual clinical review. After adjudication, 2 of 5 patients in the acalabrutinib group and 2 of 3 patients in the comparator group were determined to have fatal VA or cardiac-related SD. Nonfatal VAs were reported in 11 (0.8%) patients in the acalabrutinib group and 3 (0.5%) patients in the comparator group. When PVCs were excluded, 2 patients in each group (acalabrutinib, 0.2%; comparator, 0.3%) had nonfatal VAs. These nonfatal VAs consisted of ventricular fibrillation (acalabrutinib, n=2 [grades 2 and 4]; comparator, n=1 [grade 4]) and unspecified VA (comparator, n=1 [grade 1]). Although the acalabrutinib group had a lower exposure-adjusted event rate per 100 patient-years than the comparator group, relative risk did not favor either group. With both fatal and nonfatal VAs (with or without PVCs), time to event was notably longer with acalabrutinib than with comparators ( Table 1). A sensitivity analysis excluding the ibrutinib-treated patients from the comparator cohort yielded overall similar results (data not shown). Conclusions: This pooled analysis of prospective acalabrutinib clinical trials demonstrates that the risk of VA and SD with acalabrutinib is low and similar to that of standard-of-care therapies when adjusted for exposure. The current analysis with more than 1200 patients treated with acalabrutinib points to favorable safety outcomes and no specific trend with SDs and VAs. Additional analyses with larger cohorts from the clinical development program and all postmarketing sources will continue to further characterize the safety profile of acalabrutinib.

Abstract 17185: Percutaneous Intervention in Chronic Total Coronary Occlusion: Impact on Ventricular Arrhythmia and Mortality Compared to Medical Therapy

Background: The incidence of ventricular arrhythmias (VA) in patients with chronic total coronary occlusions (CTO) in the absence of advanced left ventricular dysfunction is not well described. Moreover, little is known about how revascularization may impact VA in this population compared to medical therapy alone. Methods: In this single-center retrospective cohort study from January 2010 to January 2019. We identified 100 patients with CTO on cardiac catheterization with a left ventricular ejection fraction (LVEF) &gt;35% who did not undergo coronary artery bypass surgery following CTO diagnosis. Percutaneous revascularization was performed for 44 patients. The primary outcomes evaluated were VA and mortality rates at end of the study period. Secondarily, cardiovascular outcomes were compared between the intervention and optimal medical therapy (OMT) groups at the end of the study period. Survival analysis was performed via Kaplan Meier calculation for VA and mortality. Statistical analysis was performed using STATA 15 and R-studio. Results: Mean age was 59.91(± 13.05) and BMI was 31.8(± 7.41). Patients were 66% male, 64% White, and 23% Black. Baseline characteristics, use of antiarrhythmic therapy, baseline LVEF, and the number of CTOs and locations of CTOs were not significantly different between groups. During a median follow-up of 4.1(± 2.54) years, the OMT group experienced higher rates of VA (21.4% vs 7.7 %, p = 0.011), and mortality (37.5% vs 15.9%, p=0.031). Conclusion: CTO in the absence of severe LV systolic dysfunction (LVEF &lt;35%) is associated with a high rate of VA and all-cause mortality, suggesting the need for further study on the impact of CTOs and their revascularization on VA and mortality in patients with LVEF &gt;35%.

Abstract 16380: Does Non-Alcoholic Fatty Liver Disease Increase the Risk of Ventricular Arrhythmias in Patients With Heart Failure?

Background: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver and non-alcoholic fatty steatohepatitis, is associated with increased incidence of heart failure (HF). Previous studies have shown an association of NAFLD with increased incidence of ventricular arrhythmias (VAs). however, it is unknown if the increased rate of VA is related to increased HF or if from an independent NAFLD-related mechanism. Therefore, this study aimed to investigate the effect of NAFLD on VA in patients with HF. Methods: A retrospective cohort study of electronic heath records using the TriNetX Research Network was performed. Patients at least 18 years old with diagnosis of cardiomyopathy (CM) or HF were identified by ICD-10-CM codes from January 1, 2014 to December, 31, 2019. Patients were separated based on the diagnosis of NAFLD. Patients who had HF and NAFLD were propensity-score matched (PSM) using age, sex, race, hypertension, hyperlipidemia, ischemic heart disease, cerebrovascular disease, atherosclerosis, diabetes mellitus, acute or chronic kidney disease, acute or chronic respiratory failure, anemia, atrial fibrillation/atrial flutter, body mass index, corrected QT interval, presence of implantable cardioverter-defibrillator, and medications with patients with HF alone. The primary outcomes were 3-year all-cause mortality, hospital admission, and incident VAs. Results: After PSM, 50,969 pairs were analyzed. NAFLD diagnosis was associated with significantly higher odds of VA (odds ratio [OR] 2.75, 95% confidence interval [CI] 2.54-2.98, p &lt;0.0001) and hospital admission (OR 1.05, CI 1.03-1.08, p &lt;0.0001) at 3-years. No significant difference was observed in mortality (OR 0.98, 95% CI 0.95-1.01, p =0.10). Conclusion: Patients with HF diagnosed with NAFLD had significantly higher odds of VA and hospital admission but not mortality at 3-years. Future studies are needed to evaluate mechanisms of VA in NAFLD patients.

MP-453089-11 DIFFERENCES IN UTILIZATION OF PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER DEFIBRILLATORS IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY ACROSS NORTH AMERICA AND EUROPE

Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but differences in their utilization across North America and Europe are unknown. To identify cross-national differences in both utilization of primary prevention ICDs and survival free from ventricular arrhythmia (VA) in patients with ARVC. This was a retrospective analysis of ARVC patients without prior sustained VA enrolled in clinical registries in 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe. They were further stratified by their calculated 5-year VA risk (low: <10%/5y, intermediate: 10-25%/5y, high: >25%/5y) using the ARVC risk calculator (ARVCrisk.com). Differences in rates of ICD implantation and VA-free survival were assessed using the Kaplan-Meier method and log-rank testing. Differences in VA-free survival were also assessed in the subset of patients without ICD. 1,098 patients were followed for a median of 5.1 years, during which time 554 (50.5%) received a primary prevention ICD. Patients treated in Europe were more likely to be probands (61.5% vs 52.0%, p=0.002) and were diagnosed at older ages (42 vs. 32 years, p<0.001). Baseline 5-year VA risk was similar (19.5% vs 19.4, p-value 0.71). North Americans were twice as likely to receive primary prevention ICDs (13.6%/year vs. 6.4%/year, p<0.001) and had shorter times from diagnosis to ICD implantation (83 days vs. 243 days, p<0.001). Overall, 285 patients (25.9%) experienced a first sustained VA event. Rates of VA were higher in North Americans compared to Europeans (6.0%/year versus 4.2%/year, p<0.001); this increase was driven primarily by higher rates of appropriate ICD therapy in North Americans (70.7% vs 59.3% of events). In sub-analysis of patients without ICD, North Americans had higher rates of VA events than Europeans (3.4%/year vs 2.4%/year, p=0.01). When stratified by baseline VA risk, North Americans received significantly more ICDs at all risk strata despite similar rates of VA events in low and intermediate risk patients (Figure). North American ARVC patients were significantly more likely to receive primary prevention ICDs across all risk strata than their European counterparts. However, a lower rate of primary prevention ICD implantation in Europe was not associated with a higher rate of adverse VA outcomes.

PO-04-190 LONG TERM OUTCOMES OF VENTRICULAR TACHYCARDIA ABLATION IN DESMOPLAKIN ARRHYTHMOGENIC CARDIOMYOPATHY – A MULTICENTER STUDY

Desmoplakin (DSP) pathogenic/likely pathogenic (P/LP) variants have been associated with the development of highly arrhyhtmogenic phenotypes of the spectrum of the arrhythmogenic cardiomyopathy (DSP-ACM). Data addressing arrhythmic outcomes after ventricular tachycardia (VT) ablation in patients (pts) with DSP-ACM are scarce. To report on long-term outcomes of pts with DSP-ACM undergoing VT-ablation All pts with P/LP DSP variant at 8 tertiary academic institutions in North America and Europe undergoing VT ablation were included in the study. Demographic, clinical, and instrumental data, as well as all arrhythmic events including per patient rates of VA episodes/year were collected. Sustained ventricular arrhythmia (VA) episodes (defined as a combination of sustained VT, proper implantable cardioverter defibrillator (ICD) intervention, and ventricular fibrillation episodes) after index procedure were the primary outcome of the study and reported with Kaplan Meyer curves. A per-pt pre- and post- VT ablation paired comparison of VA episodes/year rates was performed as well. Nineteen DSP-ACM pts (29 [25–36] y.o.; 68.4% male; 94.7% probands) referred for VT ablation were included. At the time of index procedures, all patients had a highly arrhythmic profile with a high PVC burden and over 30 different VT morphologies (56.6% right bundle branch block (BBBB); 26.6% left BBB; 16.8% unknown)(Table1). VT ablation targets were located in the LV in 7/19 pts, the RV in 7/19 pts, and both ventricles in 5/19 pts. An epicardial ablation was needed in 14/19 pts. Over a median follow-up of 27 [20–72] months, 10/19 (52.6%) pts experienced recurrent VA episodes (Figure1-PanelA). A significant reduction in per-patient event/year pre- and post- VT ablation was observed (0.50 0.25–0.94] vs 0.14 [0–0.40]; Matched Pair Wilcoxon p=0.009) (Figure1-Panel B). VT ablation in DSP-ACM is effective in significantly reducing the VA burden of the disease. However, it is not uncommon for pts to experience VA recurrences during follow up.

Sulphonylureas versus metformin and the risk of ventricular arrhythmias among people with type 2 diabetes: A population-based cohort study.

To determine whether the use of sulphonylurea monotherapy, compared with metformin monotherapy, is associated with an increased risk of ventricular arrhythmia (VA) among patients initiating pharmacotherapy for type 2 diabetes. We conducted a population-based cohort study using electronic health data extracted from the UK's Clinical Practice Research Datalink Aurum. Using the active comparator, new-user cohort design, we compared rates of VA among patients aged 18 years or older using sulphonylurea monotherapy with those using metformin monotherapy as their initial pharmacological treatment for type 2 diabetes from April 1998 to December 2019. We used a Cox proportional hazards model with inverse probability of treatment weighting by propensity score to estimate the adjusted hazard ratio (aHR) and a corresponding bootstrap 95% confidence interval (CI) for VA with sulphonylurea monotherapy versus metformin monotherapy. The cohort included 92 638 new users of sulphonylurea and 506 882 new users of metformin. A total of 279 VA events occurred among sulphonylurea users (rate per 10 000 person-years: 25.5, 95% CI: 22.7 to 28.7) and 1537 VA events occurred among metformin users (rate per 10 000 person-years: 18.5, 95% CI: 17.6 to 19.5). Compared with metformin, sulphonylureas were associated with an increased risk of VA (aHR: 1.42, 95% CI: 1.18 to 1.69). Sulphonylureas are associated with an increased risk of VA when used as first-line therapy for type 2 diabetes relative to metformin use. This increased risk should be considered when prescribing sulphonylureas as an initial treatment for type 2 diabetes.

Abstract 12010: Efficacy and Safety of Dofetilide and Sotalol in Patients With Hypertrophic Cardiomyopathy

Introduction: Patients with hypertrophic cardiomyopathy (HCM) often have atrial fibrillation (AF) and ventricular arrhythmias (VA) requiring rhythm control. In the 2014 AF Guidelines, class III anti-arrhythmic drugs are not recommended in patients with left ventricular hypertrophy, but in the 2020 HCM Guidelines, sotalol (STL) and dofetilide (DOF) are deemed “reasonable” for rhythm control, both based on limited data. Methods: We conducted an observational study (2001-2021) of patients with HCM who were treated with DOF or STL for AF and/or VA. Baseline characteristics and drug-related adverse events were analyzed from the electronic medical record, and rates of discontinuation and arrhythmia recurrence at 1 year and by time of chart review were compared using Kaplan Meier curves and log rank test. Results: There were 21 DOF and 52 STL HCM patients with AF, and 18 STL patients with VA. At 1 year, AF patients on DOF or STL had no significant difference in rates of AF recurrence (42.9% vs 44.2%, p=0.664) or drug discontinuation (38.1% vs 29.4%, p=0.582). Recurrence and discontinuation rates of VA on STL were comparable (Figure). Over a median follow up of 1603 days (IQR 994, 4131), there was a trend toward greater efficacy for STL with respect to less AF recurrence (p=0.085) and less frequent discontinuation (p=0.153; Figure). On univariate analysis, only NYHA class predicted AF recurrence. Reasons for discontinuation were most often for inefficacy or mild side-effects. One patient with prior alcohol septal ablation who was on STL for AF developed complete heart block followed by non-sustained torsades de pointes in the setting of a severe influenza infection and later underwent defibrillator implantation. There were no other cases of pro-arrhythmia or sudden death related to DOF. Conclusions: DOF and STL are modestly effective for the treatment of AF and VA in HCM patients, with a low rate of serious adverse events.

Ventricular arrhythmias in Kearns-Sayre syndrome: A cohort study using the National Inpatient Sample database 2016-2019.

Degeneration of the cardiac conduction system resulting in complete heart block (CHB), ventricular arrhythmias (VA), and sudden cardiac death (SCD) is recognized in patients with Kearns-Sayre syndrome (KSS) and is potentially preventable with permanent pacemaker (PPM) implantation. However, other mechanisms for SCD have been proposed, and the efficacy of implanting a defibrillator instead of PPM remains to be investigated. We utilized the National Inpatient Sample (NIS) database 2016-2019 to investigate the risk of VA or dysrhythmic cardiac arrest (dCA) in KSS patients. We compared the outcomes of KSS to myotonic dystrophy (MD), a more common genetic disorder with similar clinical cardiac features and course. We identified 640 admissions for KSS. VA or dCA were lower in admissions for KSS than MD patients (2.3%vs. 4.5%, p=.009). Device implantation differed between study groups. Approximately, 70% of cases with KSS and conduction abnormalities had pacemaker(±defibrillator) on hospital discharge, compared to 35% in MD. Conduction abnormalities were associated with higher rates of VA or dCA in both study groups. None of the admissions for KSS patients who developed VA or dCA had a pacemaker, and all of them had conduction abnormalities. One-third of admissions for MD patients who developed VA or dCA had a device already implanted prior to the event. Despite its effectiveness in preventing VA, PPM remains underutilized in patients with KSS or MD who have conduction abnormalities. PPM alone do not fully prevent VA in MD patients; therefore, addition of defibrillator capacity might be necessary.

Sex differences among patients with tachyarrhythmias and bradyarrhythmias following acute myocardial infarction

Abstract Background Acute myocardial infarction (AMI) is commonly complicated by ventricular, supraventricular tachycardias and high-grade atrioventricular block (HAVB) which may result in increased morbidity and mortality. Purpose To evaluate the sex differences in tachyarrhythmias and HAVB, and their associated outcomes following AMI. Methods Using the Acute Coronary Syndrome Israeli Survey (ACSIS) survey database from 2000–2018, we analyzed the specific incidence rates for arrhythmias including: sustained ventricular tachycardia (VT), ventricular fibrillation (VF), new-onset atrial fibrillation (AF) and HAVB in men and women after AMI. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess the sex differences of in-hospital arrhythmias after AMI. Multivariate cox proportional hazard models were performed to assess the impact of arrhythmias on 1-year mortality. Results In this cohort study of 14280 patients with 3159 (22.1%) women and 11121 (77.9%) men, 316 (2.2%) experienced ventricular arrhythmias (VAs) (sustained VT or secondary VF) with similar rates among men and women (2.3% and 2.2%, respectively, p=0.62). Compared to men, women were less likely to experience primary VF (1.6% vs 2.3%, p=0.034), but more likely to experience AF (8.6% and 5.0%, p&amp;lt;0.001). 372 (2.6%) patients experienced HAVB with higher rates of HAVB in women than men (3.7% and 2.3%, respectively, p&amp;lt;0.001). After multivariate analyses, the association with primary VF was attenuated (adjusted Odds Ratio (OR) = 0.80, p=0.15) but women remained more likely to experience AF (adjusted OR =1.24, p=0.01) and HAVB (adjusted OR =1.28, p=0.04). The occurrence of VAs was found to be associated with increased mortality in both men (adjusted Hazard Ratio (HR) =3.68, p&amp;lt;0.01) and women (adjusted HR=3.87, p&amp;lt;0.01) without a significant difference between the groups (p for interaction=0.203). The occurrence of AF was found to be associated with increased mortality in both men (adjusted HR=1.64, p&amp;lt;0.001) and women (adjusted HR=1.34, p&amp;lt;0.001) with a significant difference between the groups (p for interaction&amp;lt;0.001). HAVB was found to be associated with increased mortality in both men (adjusted HR=2.31, p&amp;lt;0.001) and women (adjusted HR=2.26, p&amp;lt;0.001) without a significant difference between the groups (p of interaction=0.21). Conclusions The incidence rates of VAs after AMI were similar in men and women, except for primary VF, which was more common among men. Women experienced more AF and HAVB than men. VAs, AF and HAVB were found to be associated with increased mortality. Funding Acknowledgement Type of funding sources: None.

Ventricular arrhythmias and sudden cardiac death caused by mitral valve prolapse: should we operate and when?

Abstract Background Several autopsy and observational studies have investigated the link between mitral valve prolapse (MVP) and sudden cardiac death (SCD) due to the well accepted yet rare occurrence of complex ventricular arrhythmia (VA) in this cohort. Few studies however have investigated whether arrhythmia burden and more importantly SCD are reduced following surgical correction of MVP. Purpose To investigate the impact of mitral valve surgery (MVS) (replacement or repair) on VA and SCD in patients with MVP. Methods A systematic review of the current literature was conducted using an electronic search of the PubMed database in October 2021. Studies were included if subjects had undergone mitral valve (MV) repair or replacement with documented rates of arrythmias/SCD pre- and post-intervention. Small patient numbers in individual reports precluded formal meta-analysis and results were reported on a per study basis. Results 19 identified studies (10 cohort studies, nine case studies) comprised 1322 patients with a pooled mean age of 63.4 years and 38.9% were female. 748 of the 1322 patients underwent MVS: 263 MV repair, 18 MV replacement (one with leaflet and papillary muscle excision), two MV repair with Maze procedure, 177 percutaneous transcatheter MV repair, 45 annuloplasty with or without valve repair, and in 243 cases the surgical method was not specified. Of the 10 included cohort studies, seven of the eight which investigated rates of VA post MVS concluded there was a significant reduction, while one reported the predisposition to arrythmia persisted after relieving the abnormal mechanical effects of non-ischaemic MR (75% due to MVP). One study reported a reduction in SCD post MVS. Each of the nine included case studies showed a reduction in VA post MVS. One study showed mitral annular disjunction (MAD) was independently associated with a higher risk of arrhythmic events, this link persisting with time dependent MVS although reduced compared to medical management. Conclusions The underlying mechanisms for VA and SCD associated with MVP are not completely understood, and guidelines for the surgical correction of MVP based on arrhythmic and SCD risk are lacking. This systematic review illustrates a possible reduction in VA following MVS. Further identification of patients at risk of SCD, and potential use of risk stratification algorithms, would allow for consideration of earlier management and appropriate use of implantable cardioverter-defibrillators (ICD) placement / MVS with an expected survival benefit. Funding Acknowledgement Type of funding sources: None.

Impact of left bundle branch block in patients with takotsubo cardiomyopathy

Abstract Background Takotsubo cardiomyopathy (TCM) is a syndrome characterized by reversible left-ventricular regional systolic dysfunction in the absence of obstructive coronary artery disease (CAD). The presence of left bundle branch block (LBBB) has been described as an independent predictor of mortality in patients with CAD. One study using the National Inpatient Sample (NIS) for 2016 found that the presence of LBBB was associated with worse outcomes in patients with TCM. Purpose To better clarify the association between LBBB and various in-hospital outcomes in patients with TCM. Methods The NIS database was queried from 2016–2019 to identify all admissions with a primary diagnosis of TCM that had a cardiac catheterization to improve the specificity of the diagnosis. International classification of diseases, tenth revision clinical modification (ICD-10-CM) codes were used to divide patients based on the presence or absence of LBBB. A 1:3 propensity score matching based on age, race, gender, and risk factor stratification was used to reduce selection bias. Multivariate linear and logistic regression analysis was performed to compare various outcomes among both groups. Results A total of 27,125 patients admitted with a primary diagnosis of TCM that also underwent diagnostic coronary angiography were identified. In the study sample, 955 (3.5%) were determined to have a LBBB. After calculating propensity scores, 955 patients with LBBB were paired to 2,865 patients without LBBB. LBBB was associated with higher rates of ventricular arrhythmias (AOR=3.098, 95% CI 1.483–6.471, p=0.003); however, it was not statistically associated with cardiogenic shock, sudden cardiac arrest (SCA), acute kidney injury, acute heart failure, and hospital length of stay. In addition, there was no statistical difference in intra-hospital mortality. Conclusions LBBB is associated with left ventricular dyssynchrony. It has been proposed that intraventricular dyssynchrony might be a predisposing factor for ventricular arrhythmias (VA) and SCA. Several trials have demonstrated that cardiac resynchronization therapy alone (i.e., without defibrillation) reduces the rate of VA and SCA. The mechanism for this improvement is unclear but may be related to hemodynamic improvement from ventricular synchrony in heart failure (HF). In fact, LBBB has been reported as an independent risk factor for all-cause mortality and SCA at one year in patients with HF. Our analysis did not find any significant association between LBBB and SCA but did find an association with VA. Moreover, there were not enough events of intra-hospital mortality to assess a possible association between LBBB and mortality. Therefore, a prospective study with a longer follow-up would be needed to clarify the role of LBBB in mortality and establish causality between LBBB and VA in patients with TCM. Funding Acknowledgement Type of funding sources: None.

Longitudinal validation of the phospholamban (PLN) p.Arg14del risk model

Abstract Background/Introduction Recently, a variant-specific prediction model for PLN p.Arg14del variant carriers was developed to predict individual malignant ventricular arrhythmia (VA) risk to inform decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. This model predicts malignant VA risk from data at diagnosis, but iterative evaluation of malignant VA risk may be warranted considering that the risk factors for malignant VA are progressive. Purpose To evaluate the diagnostic performance of the PLN p.Arg14del risk model. Methods/Results Date were collected of 278 PLN p.Arg14del variant carriers at 3 year follow-up. This was considered the new baseline for the survival analysis. Patients with history of malignant VA at both baseline and during the first 3 years after baseline were excluded. At 3 year patients were aged 40.1±18.0 year and 40.7% was male. Median left ventricular ejection fraction (LVEF) was 53% and percentage with microvoltages was 10.3. During a median follow-up of 4 years (Interquartile range 1.8–6.5) 31 (11%) carriers experienced malignant VA, defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. Reevaluation of the predictors with the 3 year follow-up data revealed hazard rates that were similar to those in the original PLN p.Arg14del risk model; LVEF per 1% decrease (hazard ratio (HR) 1.10 [95% confidence interval (CI), 1.06–1.12]; p&amp;lt;0.001), premature ventricular contraction count/24h (HR 1.51 [95% CI, 1.15–1.98]; p=0.003) and the presence of low-voltage electrocardiogram (HR 12.24 [95% CI, 5.21–28.8); p&amp;lt;0.001). Negative T waves did not remain significant as a predictor. The 5-year malignant VA risk was calculated for each variant carrier, after multiple imputation for dealing with incomplete cases, by applying the PLN p.Arg14del risk model to the 3 year follow-up data. Afterwards the cohort was divided into tertiles of predicted risk. This clearly demonstrated the lowest risk tertile having a low malignant VA rate and the highest risk tertile having a high malignant VA rate, which resulted in an optimism-corrected C-statistic of 0.85 (95% CI 0.78–0.92). Conclusion The PLN p.Arg14del risk model is valid at 3 year follow-up in PLN p.Arg14del variant carriers with no history of malignant VA and can therefore be used to inform decision-making for primary prevention ICD implantation not merely at diagnosis, but also during follow-up and can be seen as a type of validation in a cohort where no other large cohort is present to perform external validation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): 1. PSIDER: From pluripotent stem cells to prime editing gene therapy for inheritedcardiomyopathies. ZOn-MW.2. PREDICT2: Predicting sudden cardiac arrest. The Dutch Heart Foundation.

The Association of Clustered Ventricular Arrhythmia and Cycle Length With ScarBurden in Cardiomyopathy.

Patients with≥2 ventricular arrhythmia (VA) events within 3months (clustered VA) have increased risk for mortality. The aim of this study was to examine the association of risk factors including scar characteristics on cardiovascular magnetic resonance imaging with clustered VA and VA cycle length in nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM). Data from 329 primary prevention implantable cardioverter-defibrillator recipients (mean age 57 years, 26% women) were analyzed from the Left Ventricular Structural Predictors of Sudden Cardiac Death study. Twenty-one patients developed clustered VA (median time 2.7 years after implantable cardioverter-defibrillator placement). Men had the greatest risk for recurrent VA. Patients with NICM and scar had the highest incidence rate of clustered VA. In patients with NICM, each 1-g increase in core scar correlated with greater clustered VA risk (HR: 1.19; 95%CI: 1.07-1.32). Gray scar was similar among subgroups. Patients with NICM with clustered VA had the longest mean VA cycle length (297 ± 40 milliseconds). Higher core scar burden correlated with longer VA cycle length inpatients with NICM (P = 0.002), and higher body mass index correlated with shorter VA cycle length in those with ICM (P = 0.02). Type of VA was similar between cardiomyopathy subgroups, and no scar pattern predominated. Clustered VA was most common in patients with NICM and scar, with greatest risk among those with larger core scar. Core scar correlated with slower VA in patients with NICM, and higher body mass index correlated with faster VA in those with ICM. Type of VA was similar by cardiomyopathy etiology, and no dominant scar pattern was associated with clustered VA.

Depolarization and repolarization dynamics after His-bundle pacing: Comparison with right ventricular pacing and native ventricular conduction.

BackgroundThe current study aimed to evaluate changes in electrical depolarization and repolarization parameters after His‐bundle pacing (HBP) compared with right ventricular pacing (RVP) and its association with ventricular arrhythmia (VA).MethodsForty‐one patients (13 with HBP, 14 with RVP, and 14 controls [AAI mode]) were evaluated. After continuous pacing algorithm, QRS duration, QT interval, QTc, JT interval, T‐peak to T‐end (Tpe), and Tpe/QT ratio were measured on electrocardiography at baseline and 1 week, 1 month, and 6 months postoperatively. We investigated VA occurrence and adverse events after implantation.ResultsAt 6 months, QRS duration was significantly shorter in the HBP (121.6 ± 15.6 ms) than in the RVP (150.1 ± 14.9 ms) group. The QT intervals were lower in the HBP (424.0 ± 40.9 ms) and control (405.9 ± 23.0 ms) groups than in the RVP (453.0 ± 40.2 ms) group. The Tpe and Tpe/QT ratios at 6 months differed significantly between the HBP and RVP groups (Tpe, 69.8 ± 19.7 ms vs 87.4 ± 11.9 ms and Tpe/QT, 0.16 ± 0.03 vs 0.19 ± 0.02, respectively). The Tpe and Tpe/QT ratios were similarly shortened in the HBP and control groups. VA occurred less frequently in the HBP (15%) and control (7.1%) groups than in the RVP (50%) group (p = 0.020). The non‐RVP group showed significantly lower rates of VA and major adverse events than the RVP group. Patients with VA demonstrated significantly longer QRS duration, QT interval, Tpe, and Tpe/QT at 6 months than those without VA.ConclusionHBP showed better depolarization and repolarization stability than RVP.

Primary results from the Japanese Heart Failure and Sudden Cardiac Death Prevention Trial (HINODE).

AimsThe HINODE study aimed to analyse rates of mortality, appropriately treated ventricular arrhythmias (VA), and heart failure in Japanese patients and compared with those in Western patients.Methods and resultsAfter treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (i) internal cardioverter‐defibrillator (ICD), (ii) cardiac resynchronization therapy (CRT) defibrillator (CRT‐D), (iii) standard medical therapy (‘non‐device’: ND), or (iv) pacing (indicated for CRT; received pacemaker or CRT pacing). Cohorts 1–3 required a left ventricular ejection fraction ≤35%, a history of heart failure, and a need for primary prevention of sudden cardiac death based on two to five previously identified risk factors. Endpoint outcomes were adjudicated by the independent committees. ICD and CRT‐D cohorts, considered as high‐voltage (HV) cohorts, were pooled for Kaplan–Meier analysis and propensity‐matched to Multicenter Automatic Defibrillator Implantation Trial‐Reduce Inappropriate Therapy (MADIT‐RIT) arm B and C patients. The study enrolled 354 patients followed for 19.6 ± 6.5 months, with a minimum of 12 months. Propensity‐matched HV cohorts showed comparable VA (P = 0.61) and mortality rates (P = 0.29) for HINODE and MADIT‐RIT. The ND cohort presented a high crossover rate to ICD therapy (6.1%, n = 7/115), and the CRT‐D cohort showed elevated mortality rates. The pacing cohort revealed that patients implanted with pacemakers had higher mortality (26.0%) than those with CRT‐Pacing (8.4%, P = 0.05).ConclusionsThe mortality and VA event rates of landmark trials are applicable to patients with primary prevention in Japan. Patients who did not receive guideline‐indicated CRT devices had poor outcomes.

Ventricular arrhythmia burden and implantable cardioverter-defibrillator outcomes in transthyretin cardiac amyloidosis.

As targeted treatments for amyloid transthyretin cardiomyopathy (ATTR-CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter-defibrillator (ICD) utilization, and their impact on survival. This is a retrospective cohort study of 130 patients with ATTR-CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation. Of 130 patients, 42 had wild-type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR-CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF>40% (67%vs. 28%, p=.001). Thirty-two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5vs. 2.8 ± 0.4 years, p=.699). High rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR-CM patients with a high rate of systolic heart failure.