Ventricular Arrhythmias Research Articles

Long-term time-to-ventricular arrhythmic event prediction using a deep learning based model on the electrocardiogram signal

Abstract Background Ventricular arrhythmias (VA) risk stratification tools in individuals without known cardiovascular disease are still insufficient. Previous studies have used convolutional neural networks (CNN) to classify VA by the end of an established follow-up period using the electrocardiogram (ECG), showing a moderate performance (area under the curve [AUC] of 0.610). We hypothesised that the appearance of the VA substrate on the ECG signal depends on the proximity of the ECG acquisition to the VA event. Thus, the performance could improve if the CNN was trained to predict time-to-VA event instead, and if the presence of censored data was considered. Purpose We developed and tested a CNN to predict time-to-VA event in middle-aged individuals without known cardiovascular disease, and we compared its performance with that from ECG indices, such as QRS duration, QT interval and T-wave morphology variations (TMV), as well as sex and age. Methods A total of 69,283 individuals without known cardiovascular disease from the UK Biobank were used as the training set. We applied 10-fold cross validation to train a CNN, where the input was a 15-second ECG at rest (lead I), and the output was ‘occurrence of VA’, ‘censored’, or ‘survival’, up to 1, 2, 3, 4, 6, 8, 10 and 12 years after the ECG acquisition. We used 15-second ECG (lead I) from an independent cohort of 17,320 individuals without cardiovascular disease also from UK Biobank as a test set, where we set a follow-up of 10 years. The above ECG indices were derived from the median heartbeat from the ECG using in-house algorithms. We derived optimal cut-off thresholds from the training test, and we evaluated the AUC, sensitivity, specificity and Cox regression hazard ratios (HR) in the test set. Results In the test set, 9,206 individuals (53%) reached the 10-year follow-up, during which 60 (0.7%) had a VA event. The AUC, sensitivity and specificity values of the CNN were 0.715, 0.881 and 0.400, respectively. These values were 0.592, 0.686 and 0.383 for the QRS duration, 0.569, 0.156 and 0.717 for the QT interval and 0.552, 0.712 and 0.350 for TMV. The combination of sex and age alone showed performance values of 0.760, 0.694 and 0.683, respectively. Survival analyses showed a HR of 3.883 (P = 3.0 x 10-7) for individuals with a CNN prediction greater than the threshold derived in the training set after adjusting for age and gender. Conclusions A CNN that is trained to predict time-to-VA event and accounts for censored data outperforms previous classification proposed models and the predictive value of individual ECG indices of risk. Although the predictive value of the CNN does not show a better long-term VA predictive value than sex and age alone, it provides a significant contribution independently from these two risk factors. Our findings support the use of the ECG to improve long-term VA risk stratification, which might be particularly useful in age- and sex-stratified analyses.

The triglyceride-glucose index, ventricular arrhythmias and major cardiovascular events in patients at high risk of sudden cardiac death

BackgroundThe association between the triglyceride-glucose (TyG) index and ventricular arrhythmias (VAs) is unclear. This study aimed to investigate the relationship between the TyG index, VAs, and major cardiovascular events in patients at high risk of sudden cardiac death (SCD).MethodsWe enrolled 1046 patients at high risk of SCD with an indication for implantable cardioverter-defibrillator (ICD) implantation at the Chinese National Center for Cardiovascular Diseases. The primary outcome was VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the ICD. The secondary outcomes were cardiac mortality, heart transplantation, and rehospitalization for heart failure.ResultsThe mean (± SD) age was 59.6 ± 14.0 years old, and 25.7% were female. During the mean follow-up of 36.1 months, 342 (32.7%) patients had VAs, and 185 (17.7%) patients had major cardiovascular events. The mean fasting glucose and triglyceride levels were 111.9 ± 42.7 mg/dL and 140.0 ± 95.4 mg/L, respectively, with a TyG index range of 6.96–11.8. In the Fine-Gray subdistribution hazard model analysis, an increase in the TyG index was associated with a significant increase in the VAs (per 1 TyG index, hazard ratio [HR] 2.95; 95% confidence interval [CI], 2.29–3.80) and secondary outcome (HR 2.84; 95% CI 1.86–4.34). When stratified into tertiles, the risk of VAs was significantly higher in the highest tertile (HR 4.08; 95% CI, 2.81–5.92) than in the lowest tertile. Analysis of the secondary outcome revealed similar findings (HR 3.18; 95% CI, 1.73–5.85).ConclusionsIn our cohort, the pre-operational TyG index is significantly associated with VAs and major cardiovascular events for patients with high risk of SCD.

Right ventricular outflow tract arrhythmias in patients with obstructive sleep apnea- electrophysiological insights

Abstract Background Obstructive sleep apnea (OSA) was associated with atrial fibrillation and heart failure. Furthermore, the arrhythmic sudden death during sleep in patients with OSA raises serious concerns. Non-ischemic ventricular arrhythmias arise frequently from the right ventricular outflow tract (RVOT). The involvement of obstructive sleep apnea in the genesis of arrhythmia (premature ventricular contraction or tachycardia) originating specifically in the RVOT is not yet coherently established. Purpose This study aims to demonstrate the possible relationship between untreated obstructive sleep apnea and the occurrence of RVOT arrhythmia and to follow the electrophysiological features and outcomes after radiofrequency catheter ablation (RFA) in patients carrying this double burden. Methods One-hundred-twelve (112) consecutive asymptomatic and symptomatic patients admitted with RVOT arrhythmia ((PVCs and VTs) underwent a sleep study (polysomnography). Apnea was set out as the cessation of breathing and hypopnea was defined as shallow, slow, and restricted breathing occurring in episodes of ten seconds or more. The patients had normal left and right ventricle ejection fractions and no structural cardiovascular disease or other known extracardiac arrhythmia predisposing conditions. No significantly elevated systolic pressure in the pulmonary artery was assessed at echocardiography. Every patient was investigated by electrophysiologic study (EPS) and RFA of the clinical ventricular arrhythmia was immediately performed. Practicing and former professional athletes were excluded. Results Seventy-eight (69 %) of the included patients had an apnea-hypopnea index > 10/h. The included patients had the following characteristics: mean age 52 ± 8 years, 62% males, 81% had a BMI >30kg/m². The cardiac electrophysiologic study did not induce sustained VTs. The distribution of the PVCs and non-sustained VTs evidenced a predilection for the superior, septal and anterior (68%) and also superior and anterolateral aspects of the RVOT (23%). Radiofrequency catheter ablation (RFA) guided by activation mapping, precocity (the site of earliest activation > 30 ms before the setting of the QRS complex) and pace-mapping were performed in all patients. Immediate success was obtained in 98 patients (88%). After a mean follow-up of 24± 6 months, 28 patients (28%) from the success arm had a recurrence of the PVCs or the non-sustained VTs, 22 patients (22%) with and 6 patients (6%) without sleep apnea. Conclusions RVOT arrhythmia genesis and relapse after successful RFA seem highly associated with sleep apnea. Furthermore, patients with sleep apnea are more prone to have recurrent arrhythmias after radiofrequency catheter ablation in the absence of appropriate control of OSA.

Efficacy and safety of ultrasound guided stellate ganglion block: developing new clinical indications beyond electrical storm

Abstract Background Percutaneous stellate ganglion block (PSGB) is recommended by the latest European guidelines for patients with drug and ventricular tachycardia (VT) ablation refractory electrical storm (ES). Yet, due to the strong antiarrhythmic potential, combined with the good safety profile, we’ve recently used it for to the prophylaxis of ventricular arrhythmias (VAs) in high-risk patients and the prophylaxis/treatment of atrial arrhythmias in patients with acute heart failure (HF). Purpose To describe our single-center experience with PSGB usage outside the conventional indication of ES. Methods We hereby describe our single center experience with PSGB from 2/2021 to 2/2024. Results 56 patients (87% male, mean age 64 ± 12 years) received a total of 91 PSGB performed with the lateral, ultrasound (US) guided technique. Most of the procedures consisted of a single bolus anesthetic injection of lidocaine plus ropivacaine, 27% in an additional continuous infusion, mainly with ropivacaine. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (61%) suffered ischemic cardiomyopathy (CMP), including 11 with an acute coronary syndrome; the rest had non-ischemic CMP. 63 PSGB (69%) were performed in patients with impending or manifested cardiogenic shock (SCAI classification B or more). Mean LVEF was 24 ± 12%. Most of the procedures (n=80, 88%) were performed due to ongoing refractory VAs, yet 6 (6%) aimed to prevent major VAs in high-risk patients, mostly in the setting of recent ES (within 1 month) and need for Levosimendan to support cardiac output, in one case due to recent stereotactic VT ablation, to prevent early VAs in the phase of acute radiation induced microvascular damage. All 6 were effective in preventing clinically significant VAs. Additionally, 5 single bolus PSGBs (5%) were performed due to atrial arrhythmias with high ventricular rate despite intravenous drugs in the setting of acute HF. Specifically, 3 patients had atrial fibrillation (AF), 1 patient runs of ectopic atrial tachycardia (AT) and 1 patient 2:1 atrial flutter. Left-sided PSGB significantly reduced (≥25% reduction) ventricular rate during AF and AT but not during the single case of 2:1 atrial flutter, in 2/3 AF cases a cardioversion into sinus rhythm occurred within 40 minutes from PSGB. Only 1 (1%) major complication occurred (respiratory arrest), that was quickly and effectively treated with lipid emulsion, while minor complications were observed in 11% of PSGBs (mostly transient left arm weakness). Conclusions Our data suggest that US-guided PSGB usage, thanks to its feasibility at bed-side and good safety profile, may expand, beyond ES, to not only VAs prevention in high-risk settings, but also to prophylaxis/treatment of atrial arrhythmias in critically ill patients with acute heart failure requiring concomitant inotropic support.

Prognostic value of synthetized right-side precordial leads in arrhythmogenic right ventricular cardiomyopathy: data from nordic, dutch, and canadian ARVC registers

Abstract Background T-wave inversion (TWI) in standard ECG leads is a proven risk marker for life-threatening ventricular arrhythmias (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC). Right-sided precordial leads (RSPL), which may be more sensitive for detection of the arrhythmogenic substrate, are rarely recorded and understudied in this context. Computerized ECG signal-processing allows synthesis of right-sided precordial ECG leads derived from standard 12-lead ECG. Objective We aimed to assess the value of TWI in RSPL, synthetized from the standard 12-lead ECG, for prediction of VA risk in ARVC patients with subtle ECG phenotypes. Methods Patients with definite ARVC by TFC2010 and no history of sustained VA prior to diagnosis from the Nordic, Canadian and Dutch ARVC registries were included. Patients with major repolarization criterion or complete right bundle branch block (RBBB) were excluded. RSPL (V3R-V6R) were derived from digitally recorded eight linearly independent leads (I, II and precordial V1 to V6) of the standard ECG using a linear ECG transformation matrix. The matrix was previously developed based on a library of body surface potential maps from a mixed group of healthy subjects and patients with cardiac diseases using multivariate linear regression and QRS-T data obtained from averaged beats of the right-sided-precordial leads and the basis leads. TWI exceeding 0.1 mV in any of the synthetized leads was tested for its ability to predict sustained VA, defined as either sustained ventricular tachycardia, appropriate ICD shock, aborted cardiac arrest, or sudden cardiac death. In a similar manner, the value of TWI in any of the inferior leads III, aVF or II was assessed. Hazard ratio was calculated using Cox regression analysis adjusted for age, sex, and proband status. Results In total, 144 patients without prior VA history were identified. After exclusion of patients with major repolarization criterion (n=37) and RBBB (n=11), 96 patients comprised the study group (mean age 40±16, 42% female, 41% probands, 48% ICD carriers). Fifty-nine patients (62%) had TWI in one or more synthetized RSPL and 33 patients (34%) had TWI in any of the inferior leads. During 10 years of follow-up, 11 patients (12%) developed VA. Kaplan-Meier curve analysis showed significant association between the presence of TWI in at least one of the RSPL and the risk of VA, which remained an independent predictor in the adjusted Cox regression analysis (HR 10.6, 95%CI 1.3-84.4, p=0.026). TWI in any of the inferior leads was not associated with the risk of VA in this cohort (HR 1.2 95%CI 0.26-5.42). Conclusions Synthetized right-sided precordial leads appear to contain information potentially useful for refining risk stratification of primary prevention ARVC patients with a subtle ECG phenotype, in whom traditional repolarization markers, such as major repolarization criterion or TWI in inferior leads, are not informative.

Cardiovascular etiologies and risk factors of survival outcomes after resuscitation for out-of-hospital cardiac arrest: data from the KoCARC registry

Abstract Background The outcomes and characteristics of out-of-hospital cardiac arrest (OHCA) vary across geographic regions. The etiologies and prognoses of OHCA in Asian populations remain less established. This study aimed to investigate the etiologies and clinical characteristics of patients successfully resuscitated after OHCA and identify predictors of survival outcomes. Methods Data were extracted from a South Korean multicenter prospective registry of OHCA that included 64 tertiary hospitals from 2015 to 2018 (n=7577). The primary outcome was in-hospital mortality, and secondary outcome was the grade-1 cerebral performance category (CPC) score at discharge. Results Of the 7577 patients, 2066 achieved return of spontaneous circulation (ROSC) and were hospitalized and 915 (44·2%) presented with ventricular arrhythmia (VA) as their initial rhythm or on admission. The leading cause was obstructive coronary artery disease (n=413; 20·0%). Sudden unexplained death syndrome (SUDS) accounted for 67·5% of survivors, which were significantly lower with VA (82·7% vs. 48·3%, p<0.001). VA was an independent predictor of in-hospital mortality (adjusted hazard ratio [aHR] 0·72, 95% confidence interval 0·60–0·87) and the grade-1 CPC score at discharge (aHR 3·63, 95% CI 2·56–5·15). Other predictors of the primary outcome included age, ROSC on arrival, total arrest time, alertness on admission, extracorporeal membrane oxygenation use, targeted temperature management, implantable cardioverter defibrillator use, and coronary vasospasm. Conclusions SUDS was common in patients with ROSC after OHCA and thus needs to be evaluated comprehensively. VA was independently associated with favorable survival outcomes at discharge. Further management may improve clinical outcomes in patients with OHCA, particularly those with VA.

Atrial and ventricular arrhythmias in young, lifelong and retired elite endurance athletes

Abstract Background Whilst endurance athletes are known to have an overall higher prevalence of atrial fibrillation (AF), the prevalence of other non-sustained and sustained atrial arrhythmias (AAs) and ventricular arrhythmias (VAs) remains poorly defined. Purpose We aimed to define the prevalence of non-sustained and sustained AAs (including AF) and VAs in a healthy cohort of young, lifelong and retired elite endurance athletes. We also sought to assess associations between arrhythmias, fitness and measures of cardiac structure. Methods Holter monitors in healthy endurance athletes (n=288) from an international cohort of elite endurance athletes (the Pro@Heart consortium) were analysed for the presence of sustained and non-sustained AAs and VAs. Athletes were sub-divided into young elite athletes (n=176) and former elite athletes (n=112) of which 60 were lifelong (≥2.5 hours/week) and 52 retired (<2.5 hours/week) athletes (determined by current high-intensity exercise activity). Each athlete underwent cardio-pulmonary exercise testing, echocardiography and contrast-enhanced cardiac MRI. Participants with known structural or electrical cardiac disease were excluded. Independent T-test / One-Way ANOVA (parametric data) or Mann-Whitney U / Kruskal-Wallis Tests (non-parametric data) assessed for differences between the groups. Results Young athletes (n=176, 70.5% male) were significantly fitter with a greater degree of cardiac remodelling as compared with lifelong (n=60, 63.3% male) and retired (n=52, 82.7% male) athletes (Figure 1). The prevalence of non-sustained AAs (young: 4.0% vs lifelong: 66.7% vs retired: 61.5%, p<0.001), sustained AAs (young: 0.6% vs lifelong: 8.3% vs retired: 15.4%, p<0.001) and non-sustained VAs (young: 1.7% vs lifelong: 18.3% vs retired: 23.1%, p<0.001) was higher in lifelong and retired athletes compared with young athletes (Figure 2). Non-sustained VAs were predominately monomorphic (85%), short and moderate rate (median duration 2.8 seconds and heart rate 154 beats per minute). No athletes developed sustained VAs and/or sudden cardiac arrest. Young athletes had less VAs that were multifocal in origin compared with lifelong and retired athletes (young: 29.5%, lifelong: 37.3%, retired: 53.5%, p=0.027). There was no difference in prevalence of any arrhythmia between lifelong and retired athletes. There were no significant correlations between arrhythmias and fitness or cardiac imaging parameters. Conclusion Healthy athletes have a significant prevalence of non-sustained atrial and ventricular arrhythmias and sustained atrial arrhythmias that is more prevalent in older athletes. In older athletes, the prevalence of arrhythmias is similar regardless of whether athletes are actively engaged in training or retired suggesting that pro-arrhythmic remodelling in athletes is sustained, not immediately reversible and may be minimally responsive to detraining.Arrhythmias and cardiac imagingArrhythmias amongst athlete groups

High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: a multicenter cohort study and review of the literature

Abstract Background Patients with RBM20 cardiomyopathy commonly experience malignant arrhythmias, sudden cardiac death (SCD), and progressive heart failure (HF). Objective The aim of this study is to investigate genotype-phenotype correlations, clinical outcomes and causes of death in patients with RBM20-associated cardiomyopathy in a multicenter cohort, combined with an overview of the current literature. Methods This international, multicenter cohort included all patients with cardiomyopathy who had a pathogenic (P) or likely pathogenic (LP) RBM20 variant. For survival and regression analysis, we matched a control group based on sex, age, and presence of left ventricular dysfunction. Additionally, we conducted a literature search on studies investigating RBM20-associated cardiomyopathy. Results Sixty-two patients (45% male) were included in the study, with a mean age of 42 ± 15 years at presentation. Of the LP/P RBM20 variants identified, 9 were novel. Eleven variants were truncating, while the remaining variants consisted of missense and splice-site variants. Patients with a truncating variant who developed HF were on average older at the time of diagnosis compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p=0.01). After a median follow-up duration of 5.0 [1.0 – 10.5] years, 21 (34%) patients reached the composite endpoint of ventricular arrhythmias (VA), implantable cardioverter-defibrillator therapy, heart transplantation (HTx), left ventricular assist device (LVAD) implantation, or cardiovascular death. Of these, 19 (31%) patients experienced malignant VA (mean age 45 ± 15 years, 63% males). Males were at higher risk for the composite endpoint (log-rank p= 0.02), particularly for VA (log-rank p=0.007). The literature review analyzed 34 studies with a total of 678 patients, of whom 53% were male. In these studies, 123 (24%) patients experienced a VA, 58 (12%) underwent HTx or were treated with LVAD, and 52 (11%) died. Conclusion In this multicenter study the patients carrying a LP/P variant in RBM20 variants had a severe phenotype, with a high incidence of VA, particularly in males. Additionally, this study presents 9 novel DNA variants, of which 8 were truncating, and were mainly observed in older individuals. Finally, we report a lower mortality rate compared to the literature, possibly due to a higher number of heart transplantations performed in our patient cohort.Survival composite endpoint for sex

Incidence and characteristics of premature ventricular beats in competitive athletes at preparticipation exercise testing

Abstract Introduction The European Society of Cardiology preparticipation screening (PPS) protocol for athletes includes history, physical examination and resting ECG only. However, adding exercise testing (ET) aimed at evaluating ventricular arrhythmias (VAs) inducibility may increase the chances to identify cardiac diseases at-risk of sudden death that would otherwise be missed. Recent studies showed that the risk that premature ventricular beats (PVBs) at ET are associated to an underlying disease depends not just on their number but on characteristics such as morphology and complexity. However, there are no data on the incidence of at-risk PVBs at ET, thus requiring further tests to rule-out a cardiac disease, in apparently healthy athletes. Aim To assess the incidence and characteristics of VAs in a cohort of apparently healthy athletes undergoing annual PPS including ET. Methods We included a consecutive series of 1431 (24±13 year-old, 75% males) competitive athletes who underwent PPS in 2023. According to the Italian law and national guidelines, PPS must include ET with a different protocol according to age: in athletes younger than 35 years (81% of the study group) a rapid constant-load ET target at evaluating VAs inducibility was performed while in athletes older than 35 years a standard incremental ET was carried out. PVBs recorded during ET were assessed in terms of morphology, complexity and response to exercise. Results the incidence of at least 1 PVB was 14.5%, with a statistically significant increase according to age (p<0.001, Figure). If only athletes with frequent (at least 5 isolated PVBs) or complex (at least 1 couplet/triplet/NSVT) VAs are considered, the incidence was 4.3%, still with a significant increase according to age. In particular, among athletes older than 35 years, the incidence of PVBs was 34.1% and of frequent/complex PVBs was 15.2%. As shown in the table and figure, more than half of athletes with PVBs showed at-risk features such as persistence/increase (rather than suppression) of VAs during exercise and an "uncommon" morphology (i.e. different than infundibular or fascicular). Conclusions PVBs during ET for preparticipation screening occurred in a sizeable proportion of athletes, particularly in those older than 35 years, and many showed at-risk features such as complexity, uncommon morphologies or exercise-inducibility. Despite VAs at ET may be the only sign of a disease at risk of sudden death, their high incidence may substantially impact on the need for further investigations after PPS. Hence, more efforts should be put to identify which PVBs characteristics are predictive for an underlying cardiac disease, particularly in master athletes.

Identification and validation of ventricular rhythmic risk subgroups in hypertrophic cardiomyopathy by clustering analysis including left ventricular strain analysis

Abstract Background The excess mortality in hypertrophic cardiomyopathy (HCM) patients is mainly attributed to the occurrence of ventricular arrhythmia (VA).The prediction of VA remains challenging and could be improved. Purpose The study aimed to characterize the VA risk profile in HCM patients through clustering analysis combining conventional parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). Methods 434 HCM patients (65% men, mean age 56 years) were retrospectively included from two referral centers and followed longitudinally (mean duration 6 years). The validation cohort included 177 HCM patients from an other tertiary French center. 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 first endpoint for VA included suspected SCD, aborted cardiac arrest, appropriate ICD therapy (AIT), sustained ventricular tachycardia (SVT) and non-sustained ventricular tachycardia (NSVT) during follow-up. Results From the derivation cohort, 4 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) (Figure 1). These 4 clusters differed mainly by the LV mechanics. Patients from cluster 4 had a severe and homogeneous decrease of myocardial deformation (global longitudinal strain (GLS) -11%, normal value ≥ -20%) associated with LV and left atrium (LA) remodeling (left atrial 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 work 58.6 vs. 69.5%; p= 0.025). Patients from cluster 1 showed a marked deformation delay and temporal dispersion on the segmental analysis associated with a moderate decrease of the GLS (-15.3%; p <0.0001 for GLS comparison between clusters). Patients from clusters 2 and 3 had a small GLS decrease (GLS -17.2 and -16.3%, respectively) with a less severe phenotype for cluster 2 and older patients for cluster 3 (mean age 62.1 vs. 54.1 years; p < 0.0001). The clustering analysis in the validation population resulted in the creation of 4 clusters overlapping the derivation cohort with similar characteristics (Figure 2). Clusters 1’ and 4’ had a higher incidence of ventricular arrhythmia with a VA rate of 22%(5/23), 18%(16/88), 0%(0/17), and 20%(10/49) for clusters 1’,2’,3’ and 4’ respectively. Conclusion Machine-learning-based cluster analysis processing LV-LS parameters in HCM patients identified 4 clusters with specific LV-strain patterns and different rhythmic risk levels. In the future, the automatic extraction and analysis of LV strain parameters could help to improve the risk stratification for SCD in HCM patients.Clustering analysisExternal validation

Impact of surgical technique on postoperative ventricular arrhythmias in arrhythmic mitral valve prolapse

Abstract Background Mitral valve prolapse (MVP) is associated with progressive mitral regurgitation (MR) requiring surgical correction. A subset of patients with MVP may also constitute an "arrhythmic" phenotype suffering from malignant ventricular arrhythmias (VAs). Purpose To assess the impact of surgical technique for correction of degenerative MR including repair using artificial chords, repair with resection and mitral valve replacement (MVR) on longitudinal risk of VAs in patients with arrhythmic MVP. Methods Patients who had undergone mitral valve surgery for MVP with moderate to severe degenerative MR between 2010-2022 at a university hospital in Sweden were retrospectively included. Patients with ischemic heart disease, primary cardiomyopathy, channelopathy, or endocarditis were excluded. To examine changes in VAs (defined as sustained- or non-sustained ventricular tachycardias) as assessed by continuous Holter monitoring before and after surgery, generalized estimating equation (GEE) models were performed to account for the correlations between repeated monitoring in each patient and for differences in the time of measurement. Results Of 599 patients undergoing mitral valve surgery, 423 (71%) underwent repair using artificial chords, 62 (10%) repair with resection and 114 (19%) MVR. For those presenting with symptoms such as palpitations, presyncope, and/or syncope, Holter monitoring was conducted before (n=171; 29%) and/or after mitral valve surgery (n=184; 31%) (Figure 1). The distribution of VAs before and after surgery, stratified by surgical technique, is illustrated in Figure 2. In GEE models, repair using artificial chords was associated with increased postoperative VAs compared with the other surgical techniques (OR 2.14; 95% CI 1.19-3.83; p=0.01), repair with resection with reduced postoperative VAs compared with the other surgical techniques (OR 0.15; 95% CI 0.04-0.61; p=0.01), and no change in postoperative VAs was observed for MVR compared with the other surgical techniques (OR 0.724; 95% CI 0.39-1.35; p=0.31). The results remained similar after adjustment for age, sex, myxomatous disease/fibroelastic deficiency or bileaflet prolapse. Conclusion In patients with symptoms of palpitations, presyncope and/or syncope before or after mitral valve surgery, repair using artificial chords was associated with an increased risk of postoperative VAs. Prospective studies including continuous monitoring before and after surgery are needed to confirm these findings.

Sudden cardiac death in acute coronary occlusion: potential roles of sino-atrial nodal artery and conus artery

Abstract An estimated 80% of sudden cardiac death (SCD) is due to coronary artery disease1. Ventricular arrhythmia (VA) is most commonly associated with LAD infarctions, likely due to the larger extent of affected myocardium, but non-LAD territory infarctions also present with VA. We propose two potential contributors, the sinoatrial nodal artery (SANa) and conus artery (CA). We retrospectively analyzed 2 cohorts of patients presenting with STEMI complicated by SCD due to VA, and whether these arteries were compromised in non-LAD territory STEMI, compared with uncomplicated STEMI. In the first, cohort A, we compared 127 consecutive STEMI patients presenting with cardiac arrest, with 100 uncomplicated STEMI. SANa and CA involvement was assessed in patients presenting with non-LAD territory STEMI. In the second, cohort B, we looked at patients presenting with inferior STEMI involving the RCA only, 20 complicated by aborted SCD due to VA compared with 24 uncomplicated patients. Cohort A (see table) showed a preponderance of single vessel and proximal LAD culprits in the arrest group and a significant number of non-LAD culprits. The extent and complexity of coronary disease and amount of myocardium at risk, reflected in SYNTAX and modified Jeopardy scores, were not significantly different between arrest and non-arrest groups. In those with RCA or Circumflex culprits, 77% in the Arrest group had the SANa arising from the culprit vessel, with only 33% of patients in the Control group, p<0.005. In cohort B, 70% of arrest and 21% of non-arrest patients had SANa involvement, p<0.005. In this cohort, we also observed that 74% of the arrest patients had CA involvement, compared with only 21% of Control patients, p<0.005. There were no significant differences in heart rate nor incidence of complete heart block and atrial arrhythmia in either cohort. There was significantly more ST elevation in standard leads V1-V2, suggesting RVOT ischemia, in those with aborted SCD and RCA culprit in both cohorts (cohort B: Arrests 85% vs non-arrest 21%, p<0.005. The SANa arises from the proximal RCA in 60% of people, and 40% from the left system. Transient ischemia leading to sinus bradycardia may not result in as marked QT prolongation compared with AV block at comparable heart rates, but in the ischemic environment, with hypotension provoking sympathetic upregulation, may lead to enough repolarization heterogeneity to induce VA. The CA arises from the RCA in 50% or more, and otherwise from the right coronary sinus, supplying the RVOT, a region prone to arrhythmogenesis, even in structurally normal hearts, more so if ischemic. Recognizing the potential role of these arterial branches in the VA mechanism would alert operators into preserving their patency. Transient disturbances may not translate into long term adverse outcomes, but whereas permanent damage to the SAN is more readily remedied, further study is needed to assess any long-term sequelae of RVOT infarction.

Efficacy of percutaneous stellate ganglion block according to ventricular arrhythmia cycle length: a post-hoc sub-analysis of the STAR study

Abstract Background Percutaneous stellate ganglion block (PSGB) is an effective treatment for patients with electrical storm (ES). However, literature is scarce about a possible relation between ventricular arrhythmias’ cycle length and the effectiveness extent of PSGB. Purpose To assess whether the PSGB efficacy is affected by the arrhythmias’ cycle length prior to the procedure. Methods This is a post-hoc sub-analysis of the STAR study (STellate ganglion block for Arrythmic stoRm), a multicentre observational study aimed to assess PSGB’s effectiveness and safety in ES patients [1]. According to both the type and the median cycle of the latest ventricular arrhythmia before PSGB we considered 3 groups: ventricular fibrillation (VF), fast ventricular tachycardia (VT) and slowVT. The primary outcome is the number of treated arrhythmic episodes (with ATPs and/or DC-shocks) in the hour immediately after the PSGB as compared to the hour immediately before. The secondary outcome was the extent of the reduction of the number of ATPs/DC-shocks delivered from the hour before to the hour immediately after the PSGB. Results The original study included 184 PSGBs performed on 131 patients. We excluded 32 PSGBs with a continuous infusion and 13 PSGBs with an unknown VT cycle. The median VT cycle was 375 msec, so the final dataset of 139 PSGBs from 112 patients was divided as follows: 51 VF; 44 fastVT (VT cycle <375 msec) and 44 slowVT (VT cycle ≥375 msec). The number of treated arrhythmic episodes in the first hour after every PSGB was significantly lower compared to the first hour before in all the three groups [VF: 0 (IQR, 0-1) vs 5 (IQR, 2-8), p<0.001; fastVT: 0 (IQR, 0-0) vs 1 (IQR, 0-6.5), p<0.001; slowVT: 0 (IQR, 0-0) vs 1 (IQR, 0-4.5), p=0.001] (Figure 1). The Hodges-Lehman median difference of treated arrhythmic episodes between the hour after and before the PSGB was significantly higher in VF group [-4 (-3 to -6)] than in the fast-VT [-2 (-1 to -4)] and slow-VT [-1 (0 to -2.5)] (Figure 2). Analysing the reduction (delta less than zero) of the number of ATPs/DC-shocks from the hour before to the hour immediately after the PSGB, a significant trend was observed across the three groups (Jonckheere-Terpstra trend p<0.001) and a significant difference was observed comparing slow-VT vs VF [0 (IQR, -3 to 0) vs -4 (IQR, -7 to -1)] and fast-VT versus VF [-1 (IQR, -4.5 to 0) vs -4 (IQR, -7 to -1)], but not comparing slow-VT versus fast-VT [0 (IQR, -3 to 0) vs -1 (IQR, -4.5 to 0)]. VF was a predictor of the reduction of treated arrhythmic episodes at univariable analysis and after correction for the number of treated arrhythmic episodes in the hour immediately before PSGB and of left ventricular ejection fraction (OR 7.8, 95%CI 2.1-28.6). Conclusion PSGB is an effective treatment for ES in patients with all type of ventricular arrhythmias. However, its effectiveness was more pronounced in patients with VF or rapid ventricular tachycardia.

Biventricular modelling for investigating ventricular arrhythmias in silico

Abstract Background Ventricular arrhythmias have a significant incidence rate worldwide and may potentially lead to sudden cardiac death in severe cases. Despite therapeutic advancements, the intricate mechanisms dictating these arrhythmias remain elusive. Biventricular modelling and deep learning provide a way to investigate the complex electrophysiological substrates underlying cardiac arrhythmogenesis. Purpose This study aims to develop and validate a patient-specific biventricular computational modelling pipeline for simulating ventricular arrhythmias in silico. We provide a comprehensive platform for understanding the initiation, propagation, and treatment response of various ventricular arrhythmias. Methods To facilitate large-scale computational experiments and personalised model predictions within clinical timeframes, it is imperative to establish a rapid and reproducible modelling framework. First, we constructed biventricular volumetric models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) data from the Cardiac Atlas Project (2018 Atria Segmentation Challenge), and then we calculate biventricular coordinates to facilitate data registration between measures, and fibre and fibrosis inclusion. We also apply the pipeline to cardiac magnetic resonance (CMR) data and electrocardiogram recordings from UK Biobank. Results We have successfully developed a pipeline for constructing biventricular volumetric models and efficiently processed biventricular coordinates (Figure). By systematically exploring interactions between ventricular regions, the model may identify critical factors contributing to arrhythmia susceptibility and guide personalised therapeutic strategies. Furthermore, the model may provide insights into the efficacy of antiarrhythmic interventions, ablation techniques, and device therapies, facilitating the development of precision medicine approaches. Conclusions We demonstrate a pipeline for constructing patient-specific biventricular computational models at scale from imaging data and apply this to LGE-MRI data and UK Biobank CMR data. These biventricular models enable investigation of the complex mechanisms of ventricular arrhythmias, providing novel insights for clinical decision-making and treatment strategies.

Long-term cardiovascular outcomes of patients experiencing intra-cranial hemorrhage with or without acute cardiovascular events

Abstract Background Acute cardiovascular (CV) events would happen during the acute stage of ischemic stroke or intra-cranial hemorrhage (ICH), so called "Stroke-Heart Syndrome". However, long-term outcomes of patients who experienced acute CV events during the acute stage of ICH were unclear. In the present study, we aimed to report and compare long-term prognosis of patients with or without acute CV events after ICH. Methods A total of 104,955 patients who experienced ICH and survived longer than 90 days without past history of acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF) and ventricular arrhythmia (VA) were identified from the Taiwan National Health Insurance Research Database. Among them, 1,888 patients experienced CV events (AMI, HF, AF or VA) within 90 days after ICH, while 103,067 did not. Results Compared to patients without acute CV events, patients with acute CV events were older (73.53 vs 62.46 years, p<0.001), less males (57.89% vs 61.83%, p<0.001) and had more comorbidities , such as hypertension (77.17% vs 61.58%), diabetes mellitus (35.81% vs 26.54%), vascular diseases (3.5% vs 2.02%) and chronic obstructive pulmonary disease (15.57% vs 9.88%), all p<0.001. Compared to patients without acute CV events, those experiencing acute CV events had a higher adjusted risk of ischemic stroke (adjusted hazard ratio [aHR] 1.564), recurrent ICH (aHR 1.266), HF (aHR 4.693), AF (aHR 19.116), VA (aHR 3.485), AMI (aHR 2.463), sudden cardiac death (aHR 1.609) and mortality (aHR 1.855)(Figure). Conclusions Acute CV events occurring during acute stage of ICH were not a benign course simply related to acute stress and were associated with a poor long-term outcome. How to improve long-term clinical outcomes of these patients deserves more attentions, efforts and studies involving both cardiologists and neurologists.

Vector Field Heterogeneity (VFH) as a novel quantitative marker of electrical disarray in Arrhythmogenic CardioMyopathy (ACM) with ventricular tachycardia

Abstract Background ACM is a hereditary condition characterized by fibrofatty infiltration and replacement of cardiac myocytes predominantly presenting with ventricular arrhythmias (VA). Cardiac imaging allows for detailed structural phenotyping of scar patterns in ACM. Yet, there is a lack of tools to objectively quantify the electrical substrate alterations that may enable a more precise identification of critical sites that predispose to VA. Purpose To quantify locally disorganized cardiac electrical propagation wavefronts using the Vector Field Heterogeneity (VFH) metric from high-density multi-electrodes in patients with ACM with VT and compare to healthy controls. Methods High density epicardial substrate maps acquired with a 16-pole grid catheter during SR or RV pacing in patients with ACM with VA, who underwent clinically indicated catheter ablation, were retrospectively reviewed. Patients with structurally normal heart and idiopathic VA with epicardial ablation were analysed as a control group. Unipolar contact mapping data was exported & processed offline. From the 4×4 electrode array EGMs, vector maps of the directions of electrical propagation for recorded sites were computed. The VFH was then computed as a quantitative measure of local heterogeneity of propagation, with higher VFH expected to correlate with sites of (micro)structural tissue alterations. VFH was compared between ACM and control patients as well as at sites of normal, border zone & scar based on omnipolar voltage in ACM patients (>1.5mV, 0.5mV–1.5mV, <0.5mV, respectively). Results 10 patients with ACM (70% male, aged 52 ±18 years, ARVC 70%, biventricular 30%, RVEF 40.7±4.7%, LVEF 66±12%) and 2 patients with structurally normal heart (female, 38 & 61 years) were included. Epicardial maps had an average of 9258 ±5412 EGM points. Median VFH was statistically significantly higher in the ACM cohort compared to control for global maps (0.33±0.33 vs 0.13±0.22, p<0.001) and at sites with voltage >1.5mV (i.e. greater disorganization in ACM, p<0.001). In ACM, assessment of VFH according to omnipolar voltage sites (as a surrogate of scar) showed a quantifiable statistically significant increase in electrical disorganized propagation at sites of lower voltage (<0.5mV, median VFH 0.53±0.36) compared to borderzone (0.5-1.5mV, VFH 0.29±0.41) and normal voltage (>1.5mV, VFH 0.15±0.26), p <0.001 respectively. Conclusion Heterogenous electrical propagation as quantified by VFH is significantly increased in patients with ACM at sites of scar, but importantly also in areas of normal voltages when compared to non-ACM controls, possibly indicating microstructural alterations that are missed in traditional assessments of the arrhythmogenic substrate. Identifying and quantifying disorganized conduction patterns by VFH is a promising new mapping approach that could allow improved substrate characterization. Its diagnostic value to guide ablation therapy is currently being validated.VFH Metric ACM and ControlVFH Map Examples

Ventricular parasystole as a new indicator suggesting ventricular arrhythmias in cardiac sarcoidosis

Abstract Background In cardiac sarcoidosis (CS), it is considered that inflammation occurs in localized areas such as the basal septum. Inflammation has been suggested to be associated with ventricular fibrillation (VF). Meanwhile, ventricular parasystole is strongly associated with VF in non-ischemic cardiomyopathy. However, the relationship between CS and ventricular parasystole remains unclear. Purpose The purpose is to examine the frequency of parasystole in cases of VF and ventricular tachycardia (VT) in CS, and whether there is a correlation between the inflammatory activity of sarcoidosis and the origin of ventricular parasystole. Methods We evaluated ventricular arrhythmias (VA) in a cohort of 213 consecutive cases diagnosed with CS from 1989 to 2021 (median age 69 years, 104 males, median LVEF 36%) in our center. We investigated parasystole in cases that developed VA, using 5,313 electrocardiograms, 94 Holter electrocardiograms, and 3,174 ICD interrogation records. Classic parasystole is defined as three ventricular ectopic beats with the same morphology at a fixed interval but different coupling intervals (CI) in a 10-second continuous ECG. A new definition of parasystole requires two ventricular ectopic beats with a CI difference of more than 120ms. We also investigated the correlation of the inflammation site with ECG morphology. Results VAs were observed in 95 individuals (33.7%), and 22 developed VF (23.2%). In the VF group, parasystole was observed in 12 of 22 individuals (classic: 5, new: 7), and in the VT group observed in 20 of 73 individuals (classic: 5, new: 15), with parasystole being significantly more frequent in the VF group (P=0.018) and classic parasystole (P=0.033). In VF patients with recorded 12-lead ECGs of parasystole, the inflammation site on PET within 3 months of the VA and PVC origin matched in all 4 out of 4 cases, but no VF starting from ventricular parasystole ectopic beats was recorded. Conclusion Ventricular parasystole was detected in 54.5% of CS patients with VF. There is a possibility that the presence of parasystole and the inflammatory activity in the CS can predict the occurrence of VF.

Preliminary results of the non-invasive cardiac radioablation for ventricular tachycardia study; an in silico dosimetric comparison of photon vs proton radiotherapy for ventricular arrhythmias

Abstract Background Stereotactic arrhythmia radio-ablation (STAR) has been proposed as an alternative treatment for refractory ventricular arrhythmias (VA) in patients who are unsuitable or refractory to standard catheter ablation (CA). It consists in the application of external beam radiotherapy in a single dose of 25 Gy to the target areas. Most of the STAR treatments performed so far used photon radiotherapy. As compared to photons, particle therapy with protons, based on its finite penetration depth in tissue, might have the potential to reduce the dose to surrounding healthy tissues thus lowering the risk of side effects. Purpose The purpose of this in silico simulation study was to evaluate the feasibility of STAR with protons in patients with VA and to compare the doses of the organs at risk (OARs) in photon and proton treatment plans. Methods 14 patients (11 males) candidates to standard CA for VA were enrolled. ECG gated CT scans in expiratory breath-hold, and standard electroanatomical mapping were performed in each patients to reconstruct a 3D bipolar voltage map and identify the ablation target. Based on the information obtained by the contouring of the ablation target three treatment plans were simulated: one with photons, and two with protons - with and without cardiac gating- to assess the doses at the OARs. Results The median age was 68.5 (63.25-71.5), all patients had a history of recurrent VA and the indication for treatment with CA. 7 patients had an ischemic cardiomyopathy, 4 an idiopathic cardiomyopathy and 3 ventricular ectopic beats without structural heart disease. The mean left ventricular ejection fraction was 40±11% and 8 out of 14 patients were ICD carriers. Both photons and protons treatment plans reached the goals for target coverage (25 Gy on 98% of the target volume). A statistically significant reduction in the mean maximum dose (Dmax) to some OARs was observed in proton compared to photon plans (see table 1). Specifically, the Dmax delivered to the mitral valve, vena cava, descending aorta, esophagus and to the lungs have been largely reduced with the proton plans. However, in some specific cases, a higher maximum dose was observed for protons in structures close or overlapping with the target, mainly due to the need of an additional margin in the treatment plan to account for proton range uncertainty. The use of cardiac gating did not show a significant dose reduction to OARs compared to the non-gated proton plan. Conclusion The preliminary results of our in silico simulation study suggest that STAR therapy with the use of protons might be associated with a significant dose reduction to the surrounding organs. Nevertheless, the choice of the best treatment should be evaluated on a case by-case strategy since some specific cases may be better suitable for photon treatment.Table 1

Fully automated measurements of echocardiographic mechanical dispersion using deep learning: enhanced prediction of ventricular arrhythmias in a large heart failure cohort

Abstract Background Assessment of left ventricular (LV) myocardial deformation by strain echocardiography has shown improved prognostic value over LV ejection fraction (LVEF). Mechanical dispersion (MD) by strain reflects deformation heterogeneity. Also, MD is a marker of ventricular arrhythmia (VA) that improves risk prediction independently of LVEF in patients with heart failure. However, to analyze MD is time consuming and operator-dependent, and clinical use remains limited. Purpose We aimed to investigate the performance of a novel deep learning (DL) based method for fully automated measurements of MD and evaluate its prognostic utility in patients with heart failure compared to a conventional speckle tracking application. Methods In this prospective multicenter follow up study, the IMPROVE study, we consecutively included patients with recently diagnosed heart failure of all cause with LVEF ≤ 40%. Echocardiograms, ECG, blood samples and clinical data were acquired during index hospitalization. All patients were treated according to contemporary guidelines with optimal medical therapy and revascularization if necessary. Two experienced cardiologists recorded all echocardiograms using Vivid E9 or E95 scanners. We obtained data regarding sudden cardiac death, ventricular arrhythmia and appropriate shock from the ICD from medical records and ICD recordings. The primary endpoint was sudden cardiac death or ventricular arrhythmia (SCD/VA) during follow-up. The prognostic value of DL-based and reference MD measurements was assessed through survival statistics. Results We included 492 patients (mean ± SD 73 ± 13 years old, 32% females). Follow-up time was median (IQR) 5 (3) years. The incidence of SCD/VA was 9% (n=45). Patients with MD ≥70ms had increased risk of SCD/VA both by DL-based and reference measurements (both p <0.001). Furthermore, automated MD measurements using DL had higher prognostic value (HR 4.3) compared to manual reference measurements (HR 3.1) (p <0.001). Conclusion Fully automated measurements of MD using a novel DL method was fast, feasible, and improved prediction of SCD/VA in patients with heart failure and reduced LVEF. The integration of DL measurements may facilitate the clinical implementation of MD assessment and improve risk prediction in echocardiography.

Comorbidities and use of proarrhythmic drugs in patients with torsade de pointes arrhythmia

Abstract Introduction Drug-induced long QT interval syndrome (LQTS) is a risk factor for torsade de pointes (TdP) ventricular arrhythmia. Combining several QT-prolonging drugs can also increase risk. Clinical decision support systems (CDSS) can help prescribers assess the risk for TdP associated with drugs. Use of combination of drugs and prevalence of other risk factors is not fully known in TdP . Purpose To describe 1) comorbidities (risk-diagnoses) 2) dispensed prescription drugs and their risk for TdP (risk-drugs) using two different CDSS. The hypothesis was that individuals with TdP had risk-diagnoses and used risk-drugs. Personalized decision regarding risk stratification and medication is important to prevent TdP. Methods Patients with first episode of TdP (ICD-10 I472.C) in the National Patient Register (NPR) between 2006 and 2018 were included in this retrospective register-based cohort study. Comorbidities within 5 years prior to the hospital care episode and at the time of TdP diagnosis were retrieved. Mortality was analyzed (National Cause of Death Register). Medications dispensed within 90 days prior to TdP were retrieved (Swedish Prescribed Drug Register). Drugs were classified using 2 different CDSS (Credible Meds and Janusmed Risk Profile). Individual medication data linked with Janusmed Risk Profile gave a risk score of combination of drugs according to an algorithm. Results 762 patients with TdP were identified, most were elderly (72% ≥65 years old), 50% females. After TdP, 31 patients (4.1%) died within 7 days, 61 (8.0%) within 30 days, 87 (11%) within 90 days. Five years prior to TdP 338 patients (44%) had ≥1 risk-diagnosis (heart failure, cardiomyopathies, acute/ chronic coronary syndromes, renal failure,liver disease, LQTS, ventricular arrhythmia and/or cardiac arrest). More males vs. females had risk-diagnoses (28% vs. 22%, p<0.0015). A median of 6 drugs (IQR 2-9) were dispensed. Anti-depressants and antiarrhythmics were the most common risk-drugs. According to Credible Meds, 192 (25%) patients used ≥1 drug with known risk, 51 patients (6.7%) ≥1 drug with possible risk and 208 patients (27%) ≥1 drug with conditional risk only. 470 patients (62%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (known or possible risk). Another 88 patients had ≥1 risk-diagnosis and/or ≥1 risk-drug (conditional risk). Thus, 558 patients (73%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (Credible Meds). Analysis of combination of drugs showed that 290 patients (38 %) had drugs with increased risk, 547 patients (72%) had ≥1 risk-diagnosis and/or a combined drugs associated with increased risk (Janusmed Risk Profile). Conclusion Prior to TdP approximately a third of patients were dispensed prescription drugs with proarrhythmic risk according to two different CDSS. Almost 75% of patients were dispensed drugs associated with proarrhythmic risk and/or had other proarrhythmic risk factors. Vigilance should be undertaken to modify risk factors to prevent TdP.Baseline characteristicsRisk-drugs dispensed prior to TdP