Burden Of Ventricular Arrhythmias Research Articles

Cardiovascular Effects of Chronic Hormone Therapy: Study on Olympic Female Athletes

Female physiology is regulated after puberty by the menstrual cycle, whose hormonal fluctuations create a multitude of effects on several systems, including the cardiovascular one. The use of hormone therapy (HT) is quite common in female athletes and data on cardiovascular effects in this population are lacking. We sought to investigate the effects of HT in highly trained athletes to assess any difference associated with HT on cardiac remodelling, exercise capacity and clinical correlates. We studied 380 female elite athletes (mean age 25.5 ± 4.8) competing in endurance and mixed sports. 67 athletes (18%) were in chronic HT therapy. All athletes underwent baseline ECG, exercise ECG stress test, transthoracic echocardiogram, complete blood tests including lipid profile and inflammation indexes. The echocardiographic study showed a characteristic left ventricular (LV) remodelling, defined by lower LV mass index (86.2 vs. 92.5 g/m2, p<0.006), end-diastolic LV diameter (28.3 vs. 29.4 mm/m2, p<0.004) and end-diastolic LV volume (61.82 vs. 67.09 mL/m2, p<0.010) compared to controls, without changes in systolic function and diastolic relaxation/filling indexes. A lower burden of ventricular arrhythmias on exercise was observed in HT athletes (1.5% vs 8.6% in those without therapy, p=0.040). Linear regression analysis showed that HT had independent effect on LVEDDi (p=0.014), LVEDVi (p=0.030) and LVMi (p=0.020). In conclusion, chronic treatment with HT in female athletes is associated with less cardiac remodelling, including a lower LV cavity, volume and mass, with preserved systolic and diastolic function, and decreased burden of exercise-induced ventricular arrhythmias. HT, therefore, appears to be responsible for a more economic, but equally efficient, cardiac adaptation to intensive athletic conditioning.

Ventricular arrhythmia outcomes in hypertrophic cardiomyopathy from a high level myectomy centre

Abstract Background The presence of ≥15% late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is used as a prognostic indicator for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). [1] According to the European Society of Cardiology clinical practice guidelines (2014), septal myectomy is only indicated for symptomatic relief from left ventricular outflow tract obstruction (LVOTO) that is refractory to medical therapy, provided LVOTO gradient ≥ 50 mmHg. [2] At present, there is scarce data correlating the burden of ventricular arrhythmia and sudden cardiac death with LGE percentage or showing benefit of myectomy in reducing the burden of the same. Purpose We aimed to compare the burden of ventricular arrhythmia burden in patients with HCM who underwent septal myectomy compared with those who did not. Methods Adult patients with HCM followed in the advanced heart failure outpatient clinic at Allegheny General Hospital were included in this study. All included patients had cardiac MRI with LGE quantification and data related to cardiac events through devices placed for various indications (such as evaluation of reported palpitations, established supraventricular tachycardia, implantable cardioverter-defibrillator for primary or secondary prevention). Patients were divided into 2 groups: those undergoing myectomy (post myectomy group) and those that did not undergo myectomy (non-myectomy group). Chi square test was used to calculate incidence of premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT) and sustained ventricular tachycardia (SVT) in the non-myectomy and post myectomy group. Results 76 patients with HCM (interventricular septal thickness ≥1.5 cm and LGE positive) longitudinally followed in the Allegheny General Hospital advanced heart failure outpatient clinic from 2016 to 2022 were included. 37 patients underwent septal myectomy. Baseline characteristics of post myectomy and non-myectomy group were matched and are listed in table 1. Left ventricular mass index was expectedly higher in patients undergoing myectomy. LGE was quantified on cardiac MRI prior to myectomy (mean 16.4% in myectomy group, 14.6% in non-myectomy group). Burden of ventricular arrhythmia (PVCs, NSVT and SVT) was found to be significantly lower in the post myectomy group (n=13, 44.83%) compared to the non-myectomy group (n=36, 92.31%). None of the patients included were noted to have ventricular fibrillation or sudden cardiac death. Conclusion Septal myectomy may reduce the incidence of ventricular arrhythmia and thus impact outcomes related to sudden cardiac death. This is likely a consequence of removal of arrhythmogenic scar tissue. Larger studies are required to further evaluate the burden and correlation of ventricular arrhythmia with scar tissue volume measured on cardiac MRI.

High-intensity interval training in patients with an implantable cardioverter defibrillator: a randomized controlled study

Abstract Background Exercise is an effective treatment in a broad spectrum of cardiovascular diseases. High-intensity interval training (HIIT) has shown superior effect on cardiorespiratory fitness and equal or superior effect on morbidity and quality of life (QoL) compared to moderate continuous exercise training. However, evidence of the efficacy and risks of HIIT in patients with increased risk of ventricular arrhythmia remains limited. Purpose To evaluate the effects of HIIT on exercise capacity, QoL and burden of ventricular arrhythmias in patients with an implantable cardioverter defibrillator (ICD) with or without cardiac resynchronization therapy. Methods Patients with ischemic or dilated cardiomyopathy and ICD were randomized to a supervised 12-week HIIT program or to a control group continuing their usual exercise routines. HIIT consisted of four 4-minute intervals aiming at 85-95% of maximum heart rate (HRmax), and 3-minute active recovery aiming at 60-70 % of HRmax in between intervals, 3 times a week for 12 weeks. Primary outcomes were exercise capacity measured as peak oxygen uptake (VO2 peak) and QoL assessed with the Short Form 36 (SF-36) questionnaire. Main secondary outcome was the burden of ventricular arrhythmias analysed from remote patient monitoring data. Results Fifty-six patients were included (table 1). Three patients in the HIIT group did not complete the intervention. Two withdrew due to a knee injury and due to fear of SARS-CoV-2 exposure, respectively. One experienced an appropriate shock during exercise and was excluded from further training after clinical consideration. Fifty-three patients completed all follow-up examinations. HIIT significantly increased VO2 peak with 7.0 %, with no changes in the control group (p=0.001) (figure 1A). There was a significant increase in the SF-36 subscale scores on physical functioning (p&amp;lt;0.05), general health (p&amp;lt;0.05) and health change (p=0.001) in the HIIT group compared to the control group (figure 1B). There were no significant differences between groups in number of non-sustained or sustained ventricular tachycardias, anti-tachycardia pacing therapy or ICD shocks. Conclusions In patients with ICD due to ischemic or dilated cardiomyopathy, a supervised 12-week HIIT-program significantly increased VO2 peak and QoL without increasing the burden of ventricular arrhythmias.Table 1:Patient characteristicsFigure 1:Peak oxygen uptake and QoL

Impact on clinical outcome of ventricular arrhythmias in patients undergoing transcatheter aortic valve implantation (TAVI)

Abstract Background Transcatheter aortic valve implantation (TAVI) in the treatment of severe aortic stenosis has considerably grown in the latest years. There are limited data, however, about predictors of long-term prognosis in this population. Particularly, whether ventricular arrhythmic burden is associated with clinical outcome has poorly been investigated. Purpose The aim of our study was to investigate the association between ventricular arrhythmias and adverse clinical outcomes in patients undergoing TAVI. Methods We performed a 24-hour 3-channel ECG Holter monitoring (HM) in 267 consecutive patients who underwent TAVI for severe aortic stenosis at our Centre within 30 days from a successful procedure (average 10.2 days, range 2-30). For each patient we obtained the number of premature ventricular complexes (PVCs) and the presence of non-sustained ventricular tachycardia (NSVT, &amp;gt;3 PVCs with a rate &amp;gt;100 bpm). Frequent PVCs were defined as the presence of at least 30 PVCs per hour. We also collected clinical and echocardiographic findings for each patient. Assessment of clinical events at follow-up was performed by clinical visits or telephone interviews of patients or relatives (in case of fatal events). The primary endpoint of the study was the occurrence of cardiovascular events (CVE), a composite of cardiovascular death and resuscitation from cardiac arrest. All-cause-mortality was assessed as secondary endpoint. Survival Cox regression was applied to assess the univariate and multivariate association of clinical, echocardiographic and HM variables with endpoints. Results Clinical outcome could be obtained for 228 patients (85%), for an average follow-up of 3.5 years (range 1.0-8.6). Among these patients, frequent PVCs (≥30/hour) and episodes of NSVT at HM were found in 47 (20.6%) and 52 (22.4%) patients, respectively. CVE occurred in 26 patients (11.4%) and 63 patients died (27.6%). Frequent PVCs at HM were detected in 12 patients with (46.2%) and 35 patients without (17.3%) CVE (HR 2.29; 95% CI 1.03-5.09; p=0.04). One or more episodes of NSVT were detected in 9 patients with (34.6%) and 43 patients without (21.3%) CVE (HR 2.29; 95% CI 1.03-5.09; p=0.04), although it was not predictive of all-cause mortality (HR 1.18; 95% CI 0.48-2.77; p=0.52). Both the presence of PVCs&amp;gt;30/hour (HR 1.19; 95% CI 0.69-2.08; p=0.53) and NSVT (HR 0.93; 95% CI 0.52-1.65; p=0.22) were not significantly associated with all-cause mortality. Moreover, no clinical (age, gender, cardiovascular risk factors) and echocardiographic (aortic valve area, trans-aortic mean gradient, left ventricle mass and ejection fraction) variable showed significant association with both the primary and secondary outcome in our patients. Conclusions In our study the detection of frequent PVCs at HM after TAVI was a major predictor of CVE (cardiovascular death/cardiac arrest), suggesting that a 24-hour HM after TAVI can be helpful for risk stratification of these patients.

Impact of sodium-glucose cotransporter-2 (SLGT2) inhibitors treatment initiation on the reduction of atrial and ventricular arrhythmias in patients with implanted cardiac devices

Abstract Introduction Sodium-glucose cotransporter-2 (SLGT2) inhibitors have demonstrated benefits on survival and hospital admissions in patients with heart failure and reduced ejection fraction. However, their impact on the burden of ventricular (VA) and atrial arrhythmias (AA) is unknown. Methods Retrospective multicentric study of heart failure patients with implantable cardiac defibrillator device (ICD) from 2015 to 2020 with or without cardiac resynchronization therapy (CRT) receiving SGLT2 inhibitors. Device-registered arrhythmic events were analyzed and compared during one year following SLGT2 inhibitor initiation and during one year before initiation. Relevant VA were defined as the occurrence of any sustained VT (SVT) (&amp;gt;30 seconds), ventricular fibrillation (VF), or appropriate therapy (antytachycardia pacing or shock). All VA included all the relevant VA and the occurrence of non-sustained ventricular tachycardia (NSVT). AA included atrial fibrillation (AF) burden, and episodes of more than 24 hour of AF. Results 147 patients (67 ± 10 years, 82.3% males, LVEF 30.3 ± 11%, CRT 39.3%), were included in the study. 77.6% had complete remote tele-monitoring during the entire follow up and there was no difference in the antiarrhythmic therapy between the two periods. Following SGLT2 inhibitor initiation, there was a significant reduction in the percentage of patients with relevant VA (19.7% pre vs 10.9% post; p=0.019) and all VA (47.6% pre vs 30.6% post; p&amp;lt;0.001) (Figure 1 and 2). There was a reduction in the prevalence of NSVT (40.1% pre vs. 27.2% post; p&amp;lt;0.001), of SVT (17.7% vs 8.8%; p&amp;lt;0.001), of VF (4.1% vs 2%; p=NS) and appropriate therapies (14.3% vs 9.5%; p=NS). Among patients with any VA, there was a significant reduction in the incidence of NSVT (p&amp;lt;0.001), but not in the incidence of SVT or appropriate therapies (p=NS). There was no impact on atrial fibrillation burden or in the number of AF episodes lasting more than 24 hours (p=NS). Conclusions In our study, initiation of a SGLT2 inhibitor in patients with heart failure, was associated with a reduction in the prevalence of relevant VA and any VA, with a significant reduction in the number of NSVT per patient. There was no impact on AF burden or the number of AF episodes lasting more than 24 hours. Prospective studies should be performed to sustain these conclusions.Relevant ventricular arrhythmiasAny ventricular arrhythmia

Perfomance of sudden cardiac death prediction strategies before and after Septal Reduction Strategies in patients with Hypertrophic Cardiomyopathy

Abstract Background Actual sudden death (SD) risk stratification strategies for Hypertrophic Cardiomyopathy have not been validated for patients after a septal reduction treatment (SRT). Therefore, it is largely unresolved the quantification of the ventricular arrhythmias (VA) burden after an SRT and how risk stratification should be performed in such patients. Purpose To evaluate the performance of ESC SD Risk stratification model and AHA ACC Risk Factors for SD in the identification of patients with lethal ventricular arrhythmias after SRT. Methods Data from 11 high-volume HCM specialty centers from the international SHaRe Registry were used to describe the natural history of patients with SRT. Patients were followed from SRT until last follow-up or meeting the composite outcome of ventricular arrhythmias (sudden cardiac death (SCD), resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator (ICD) therapy). Cox proportional hazards models were used to identify predictors of prognosis and incident development. Calculation of SD score was performed before the SRT and at 1 year from the procedure. Results Of the 10385 patients part of the ShaRe Registry, 1835 (18%, 968 (53%) males) underwent a SRT during a median follow-up of 6.8 (IQR 3.4-9.8). A total of 455 (25%) had Alcohol Septal Ablation (ASA) and 1377 (75%) had myectomy. Patients who underwent myectomy were younger (49±18 vs 56±15 years, p&amp;lt;0.01), more frequent with a sarcomeric mutation (396 (29%) vs 111 (24%), p&amp;lt;0.01). Over 6.8 years after the procedure, 77 (4%) died because of HCM (0.6%/year) and 87 (5%) presented a composite VA outcome (0.7%/year). Development of the composite VA event was associated with younger age at procedure (38±20 vs 54±18 years, p&amp;lt;0.01), the development of a LV EF&amp;lt; 50% (29 (33%) vs 351 (20%), p&amp;lt;0.01), a more severely dilated LA (47±7 vs 43±11 years, p&amp;lt;0.01) and greater LV maximal wall thickness (24±6 vs 21±6 years, p&amp;lt;0.01). Significant predictor of the composite VA outcome was the presence of a LA diameter ³ 45 mm (HR, 2.6 [95% CI, 1.7–3.5]). Patients who presented the VA outocome were classified according to ESC SCD Risk pre and post SRT as: 40 (46%) as high risk, 31 (36%) as intermidiate risk, 16 (18%) as low risk pre intervention and 26 (46%) as high risk, 41 (47%) as intermidiate risk, 20 (18%) as low risk post procedure. AHA ACC SCD risk factors pre and post SRT classified patients as: 56 (64%) as class IIA 25 (29%) as Clas IIB, 6 (7%) as Class III and post SRT 42 (48%) as Class IIA, 31(36%) as Class IIB, 14 (16%) as Class III. Conclusions Current stratification strategies potentially underestimate the risk of SD pre and post SRT. Specifically, ESC SD risk strategies underperformed in the identification of intermidiate high risk patient, whereas AHA ACC were capable of identifying 84% of patients who had a malignant VA.

Modulation of myocardial inflammation, fibrosis development and ventricular arrhythmogenicity by endurance exercise in murine coxsackievirus B3 myocarditis

Abstract Aims Nonischaemic myocardial fibrosis is associated with progressive deterioration of myocardial function and forms the substrate for arrhythmias in atria and ventricles. In the absence of a specific aetiology, its origin is commonly attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often demonstrate nonischaemic fibrosis on magnetic resonance imaging. Previous translational studies have shown an adverse effect of exercise on the course of acute viral myocarditis. Nevertheless, the effect on myocardial fibrosis development, a frequent and important consequence of viral myocarditis, has not yet been investigated. In the present study, we evaluate for the first time the impact of endurance exercise on longer-term myocardial inflammation, myocardial fibrosis and arrhythmogenicity using a murine viral myocarditis model. Methods and results Male C57BL/6J mice (11 weeks of age, n=72) were randomly assigned to 8 weeks of treadmill running (EEX) or without exercise (SED). Two weeks into the study (training or control), animals were injected intraperitoneally with either coxsackievirus B3 to induce acute viral myocarditis (CVB) or vehicle (PBS). Exercising myocarditis mice showed lower mortality (11% vs. 27%), albeit without statistical significance (P=0.23). At sacrifice (i.e. 6 weeks after inoculation), prominent myocardial inflammatory infiltration and cardiomyocyte loss was observed in both CVB groups, without difference on semiquantitative histological scoring. Nevertheless, the infiltrating cells in the CVB-EEX group were more often proinflammatory in nature (predominantly iNOS-reactive macrophages and positive CD8+/CD4+ ratio) compared to these in CVB-SED (predominantly arginase-1-reactive macrophages and higher CD4+/CD8+ ratio). In addition, the EEX group showed more haemosiderin-laden macrophages and spindled fibroblasts as signs of organisation. At that time, the majority of virus was cleared from the heart. Treadmill running during myocarditis enhanced development of interstitial fibrosis (with limited or extensive distribution)(82.4% in CVB-EEX vs. 56.3% in CVB-SED; P=0.049) and perivascular and/or interstitial fibrosis with extensive distribution (64.7% &amp; 64.7% in CVB-EEX vs. 50% &amp; 31.3% in CVB-SED; P=0.048). The highest scar counts were observed in CVB-EEX, but the mean count (1.9 vs. 1.2; P=0.19) did not significantly differ between the myocarditis groups. In CVB-EEX, the lesions contained denser and more organised collagen bundles. In vivo electrophysiology studies showed similar ventricular arrhythmia inducibility (P&amp;gt;0.20) and arrhythmia burden (P=0.49) in the myocarditis groups, although the longest arrhythmias and highest cumulative burden occurred in CVB-EEX. Conclusion Endurance exercise training during viral myocarditis modulates the longer-term inflammatory process and promotes perivascular and interstitial fibrosis development, potentially enhancing ventricular arrhythmogenicity.

Abstract 18880: Ventricular Arrhythmia Prevalence and Burden in Patients With Third Generation Continuous Flow Left Ventricular Assist Devices

Background: Ventricular arrhythmias (VAs) are common in patients with left ventricular assist devices (LVADs). Little is known about the impact of third-generation LVADs (Heartmate 3, HM3) on VAs prevalence and burden. Aims : To characterize the impact of HM3 LVAD implantation on VAs prevalence and burden in patients with advanced heart failure (HF) and implantable cardioverter-defibrillators (ICDs). Methods: We included consecutive patients with advanced HF and ICDs who received HM3 devices at our center between 2016 and 2022. The study outcomes were the prevalence of sustained VAs, defined as &gt;30s VA episode detected by the ICD monitor zone or appropriately treated (ATP or shock), sustained VA burden (total number of episodes), and VA storm (≥3 appropriate ICD interventions in 24/h period). Data was collected over the 1 year before and after HM3 implantation. Results: A total of 321 patients were included (28% female, mean age 60±12 years, mean INTERMACS score 3±0.95). At 1 year follow-up after HM3 implantation, 27 patients died. A total of 128 patients (43%) had at least one sustained VA episode in the year before the HM3 implantation compared to 51 patients (17%) in the year following the HM3 (p&lt;0.001 for comparison). The sustained VA burden decreased from a mean of 3.8 events per person-year (PPY) to a mean of 0.8 events PPY (p=0.005). Similarly, appropriate ICD therapy occurred in 123 patients (38%) before implantation and 46 patients (14%) after implantation (p&lt;0.001). The burden of appropriate therapy was also reduced (from a mean of 2.57 events PPY to a mean 1.32 events PPY; p=0.03). The prevalence of VA storm was reduced from 19% to 8% (p&lt;0.001). Conclusions: In patients with advanced HF and ICDs undergoing HM3 implantation, the prevalence of sustained VAs, VAs burden, appropriate ICD interventions, and VA storm were all significantly reduced in the year following HM3 implantation.

Abstract 13790: Efficacy of Stellate Ganglion Block for Refractory Ventricular Arrhythmias: An Updated Systematic Review

Background: Stellate ganglion block (SGB) has emerged as an alternative approach to refractory ventricular arrhythmias (VAs). However, data on the outcome of SGB for refractory VAs are limited. Objective: This study aimed to assess the in-hospital efficacy of SGB in refractory VAs. Method: A systematic search was performed in MEDLINE and EMBASE according to the PRISMA guidelines from July 2017 to October 2022. Studies reporting the characteristics of in-hospital VAs before and after the SGB were included. Studies that had missing outcomes were excluded. Results: Of 515 publications reviewed, 162 patients (60.6 ± 13.6 years of age, 81.5% male) were included across 27 studies. Amongst, 103 patients (63.6%) had ischemic cardiomyopathy, and the mean ejection fraction was 29.8 ± 12.7%. Prior to the SGB procedure, 100 patients (61.7%) required two or more anti-arrhythmic medications control. Following SGB, there was a significant 92% reduction of VAs episodes from 13.9 ± 18.5 to 0.9 ± 2.1 (p&lt;0.01) during the hospitalization (31±35 days). Of the reported patients, 46.5% remained free of VAs, and 53.5% had recurrences before discharge. Among 61 patients who required additional neuromodulation after SGB in the same hospitalization, 32 patients (52.5%) received repeated SGB, 15 patients (24.6%) underwent surgical sympathectomy, and 14 patients (23%) underwent catheter ablation. Of the reported patients, 75.4% of patients survived throughout the hospital course. Conclusion: SGB significantly reduced VAs episodes in patients with refractory VAs during hospitalization. More than three-quarters of the patients survived following the SGB for refractory VAs. This highlights the potential effective role of SGB in managing refractory VAs. Figure Change in Ventricular Arrhythmias Burden after Stellate Ganglion Block

Abstract 18390: Ibrutinib Increases Ventricular Arrhythmia Burden Independently of Atrial Arrhythmia

Introduction: Use of Bruton Tyrosine Kinase inhibitors (BTKi) such as ibrutinib is frequently limited by atrial arrhythmia, possibly through off-target inhibition of C-Terminal-Src-Kinase (CSK). Whether BTKi can directly trigger ventricular arrhythmia is less clear. Case reports and retrospective analysis have suggested a link, but causal effect is not established. The association is further put into doubt by absent expression of CSK or BTK in ventricular cardiomyocytes, and absence of ventricular arrhythmia signals in meta-analyses of BTKi RCTs. Further study is critically needed. Hypothesis: Ibrutinib induces ventricular arrhythmia through a unique mechanism. Methods: We performed a retrospective crossover study of ibrutinib-treated patients with serial cardiac monitoring both on and off ibrutinib (pacemakers, loop recorders, or multiple holters) across a 10-year span in a large academic center to compare burden of atrial/ventricular ectopy on and off ibrutinib. A separate group of Chronic Lymphocytic Leukemia (CLL) patients with serial cardiac monitoring not on BTKi was used as additional controls. To determine biological correlation, we tested the ability of ibrutinib to induce arrhythmia in cultured human Induced Pluripotent Stem Cell derived ventricular cardiomyocytes (iPSC-vCMs). Results: 88% (15/17) of patients on ibrutinib with serial cardiac monitoring had increased burden of Premature Ventricular Contractions (PVCs), with an average increase of 155 PVCs/hour (p&lt;0.0001). An increase was not observed in the control cohort. Ventricular arrhythmia burden was not associated with atrial arrhythmia burden. Removing patient-related confounders, in vitro analysis of iPSC-vCMs demonstrated that ibrutinib induced arrhythmia following three days of treatment in a dose-dependent manner. Conclusions: In patients with continuous/serial cardiac monitoring, ibrutinib is associated with a significant increase in ventricular ectopy (average of 155 PVCs/hr). Lack of ventricular and atrial arrhythmia concordance suggests an alternative mechanism of arrhythmia induction. Increased arrhythmogenicity of human ventricular cardiomyocytes treated with ibrutinib indicates a direct myocardial mechanism.

Abstract 16815: Outcomes of Cardiac Sympathetic Denervation via Cautery Ablation for Ventricular Arrhythmia: A Single Center Study

Introduction: Cardiac sympathectomy denervation (CSD) has been demonstrated to reduce ventricular arrhythmia (VA) burden and to improve arrhythmia-free survival. Early evidence for the clinical antiarrhythmic benefits for CSD was established in patients with long-QT syndrome and catecholaminergic polymorphic VT (CPVT). Its benefit has subsequently been shown to extend to other undifferentiated cardiomyopathies. Hypothesis: Literature on CSD for VA has been limited due to a small number of patients. Our retrospective study is to review patients who underwent CSD for VA at our center via cautery ablation. Methods: We identified 9 patients who underwent CSD from 4/2018 to 2/2022. Electronic medical record was reviewed for clinical history and outcomes. Results: Mean age was 52±17 and 5 patients (55.6%) were male. Seven patients (77.8%) had nonischemic cardiomyopathy (NICM) and 2 patients (22.2%) had CPVT. Mean LVEF was 43±19% and 5 patients (55.6%) had heart failure with NYHA class 3±0.7. Five patients (55.6%) underwent CSD in outpatient setting and 4 patients (44.4%) had polymorphic VT. Six patients (66.7%) had prior catheter-based VT ablation, 1 patient (11.1%) had prior ganglion block, and 4 patients (44.4%) had history of VT storm. All patients were on antiarrhythmics ranging from a beta blocker monotherapy to a combination of class Ic, class III, and a beta blocker. Seven patients (77.8%) had a defibrillator prior to CSD. All patients underwent CSD (7 with bilateral and 2 with left only) without any procedural complication. Five patients (55.6%) had recurrence of VA in 423±567 days with follow-up duration of 729±478 days. Three patients (33.3%) underwent heart transplant or LVAD and three patients (33.3%) died in 426±396 days since CSD. Overall, 3 patients (33.3%) including 2 CPVT patients and one NICM patient with normal EF were free of death, sustained VT, or advanced heart failure therapies. Conclusions: CSD via cautery ablation is safe and effective for patients with refractory VA to antiarrhythmics and/or VT ablation. Success rate appeared to be higher in patients with CPVT and normal EF. Lower rate of survival and freedom from VT or transplant/LVAD compared to published literature may reflect our sick population.

Abstract 13214: Arrhythmic Burden After Bruton's Tyrosine Kinase Inhibitor Initiation and Major Cardiovascular Events

Background: Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B cell malignancies. BTKi’s also cause cardiotoxic arrhythmias, including atrial fibrillation (AF) and ventricular arrhythmias (VA). Yet, the true burden and long term effects of arrhythmias after BTKi therapy are unknown. Research Question: In patients with suspected BTKi related arrhythmias, what is the relative AF burden? Does it prognosticate future events? Methods: Leveraging a cohort of consecutive B cell malignancy patients initiated on BTKi from 2009-2020, we identified patients with available ambulatory rhythm monitors. The primary outcome was AF burden after BTKi initiation. Secondary outcomes included VA burden, conduction blocks, and other arrhythmias of probable or definite BTKi association. Observed incident AF rates and burden with next generation BTKi’s were compared to ibrutinib. Multivariable regression and survival analysis were used to define factors associated with AF related hospitalizations and major adverse cardiac events (MACE), as well as the relationship between AF burden and mortality. Outcomes were stratified by high (≥5%) vs low (&lt;5%) AF burden. Results: Of 890 BTKi treated patients, 98 wore ambulatory rhythm monitors, including 38 on next generation BTKi’s [age 67.7 years, 24.2% prior AF]. Median duration BTKi use was 34 months. Among next generation BTKi treated patients, 8.7% developed incident AF compared to 25.5% with ibrutinib ( P =0.048). Ten patients (26.3%) developed symptomatic or &gt;1% PVCs, at a mean burden of 7.1% compared to eight patients (13.3%) with mean burden 9.4% on ibrutinib. In a multivariable model accounting for traditional CV risk factors, prior AF associated with increased post BTKi AF burden. In follow up, high AF burden associated with increased MACE (HR 3.49, P =0.001) and mortality (HR 3.2, P =0.002); Figure . Conclusions: In BTKi treated patients, cardiotoxic AF burden prognosticates future MACE and mortality.

Future direction of substrate-based catheter ablation in Brugada syndrome and other inherited primary arrhythmia syndromes: Systematic review and meta-analysis.

Inherited Primary Arrhythmias Syndromes (IPAS), especially Brugada syndrome (BrS), have been associated with arrhythmogenic substrates that can be targeted through ablation. This meta-analysis evaluated the outcomes of catheter ablation (CA) in different types of IPAS based on procedural guidance and location. A systematic search was conducted across multiple databases to identify studies reporting on ventricular arrhythmia (VA) events before and after CA in IPAS, including BrS, Long-QT syndrome (LQTS), Early repolarization syndrome (ERS), and Idiopathic ventricular fibrillation (IVF). The primary outcomes were VA recurrence and VA burden, evaluated through conditional subgroup analysis. Procedural data were collected as secondary outcomes. A total of 21 studies involving 584 IPAS patients who underwent CA were included. Following a mean follow-up duration of 33.5 months, substrate-based ablation demonstrated efficacy in reducing VA recurrence across all types of IPAS [RR 0.23; 95% CI (0.13-0.39); p < .001; I 2 = 74%]. However, activation guidance ablation was found to be effective only in IVF cases. Although recurrences still occurred, CA was successful in reducing VA burden [MD -4.70; 95% CI (-6.11-(-3.29); p < .001; I 2 = 74%]. The mean size of arrhythmogenic substrate was 15.70 cm2 [95% CI (12.34-19.99 cm2)], predominantly distributed in the epicardial right ventricular outflow tract (RVOT) in BrS cases and LQTS [Proportion 0.99; 95% CI (0.96-1.00) and Proportion 0.82; 95% CI ( 0.59-1.00), respectively]. Substrate-based CA has demonstrated effective prevention of VA and reduction in VA burden in IPAS cases.

Ventricular arrhythmia burden in ICD patients during the second wave of the COVID-19 pandemic

AimCOVID-19 has been associated with cardiovascular complications including ventricular arrhythmias (VA) and an increased number of out-of-hospital cardiac arrests. Nevertheless, several authors described a decrease of VA burden in patients with an implantable defibrillator (ICD) during the first wave of the COVID-19 pandemic. The objective of this study was to determine if these observations could be transferred to later periods of the pandemic as well.MethodsWe retrospectively analyzed a total of 1674 patients with an ICD presenting in our outpatient clinic during the second wave of the COVID-19 pandemic and during a control period for the occurrence of VA requiring ICD interventions.ResultsSeven hundred ninety-five patients with an ICD had a device interrogation in our ambulatory clinic during the second wave of the COVID-19 pandemic compared to eight hundred seventy-nine patients in the control period. There was significant higher amount of adequate ICD therapies in the course of the COVID-19 period. Thirty-six patients (4.5%) received in total eighty-five appropriate ICD interventions during COVID-19, whereas only sixteen patients (1.8%) had sustained VA in the control period (p = 0.01).ConclusionIn contrast to the first wave of COVID-19, which was characterized by a decrease or least stable number of ICD therapies in several centers, we found a significant increase of VA in ICD patients during the second wave of COVID-19. Possible explanations for this observation include higher infectious rates, potential cardiac side effects of the vaccination as well as personal behavioral changes, or reduced utilization of medical services.

Performance and feasibility of three different approaches for computer based semi-automated analysis of ventricular arrhythmias in telemetric long-term ECG in cynomolgus monkeys

Computer-based analysis of long-term electrocardiogram (ECG) monitoring in animal models represents a cost and time-consuming process as manual supervision is often performed to ensure accuracy in arrhythmia detection. Here, we investigate the performance and feasibility of three ECG interval analysis approaches A) attribute-based, B) attribute- and pattern recognition-based and C) combined approach with additional manual beat-to-beat analysis (gold standard) with regard to subsequent detection of ventricular arrhythmias (VA) and time consumption. ECG analysis was performed on ECG raw data of 5 male cynomolgus monkeys (1000 h total, 2 × 100 h per animal). Both approaches A and B overestimated the total number of arrhythmias compared to gold standard (+8.92% vs. +6.47%). With regard to correct classification of detected VA event numbers (accelerated idioventricular rhythms [AIVR], ventricular tachycardia [VT]) approach B revealed higher accuracy compared to approach A. Importantly, VA burden (% of time) was precisely depicted when using approach B (−1.13%), whereas approach A resulted in relevant undersensing of ventricular arrhythmias (−11.76%). Of note, approach A and B could be performed with significant less working time (−95% and − 91% working time) compared to gold standard. In sum, we show that a combination of attribute-based and pattern recognition analysis (approach B) can reproduce VA burden with acceptable accuracy without using manual supervision. Since this approach allowed analyses to be performed with distinct time saving it represents a valuable approach for cost and time efficient analysis of large preclinical ECG datasets.

Long-term cardiac follow-up of athletes infected with SARS-CoV-2 after resumption of elite-level sports

ObjectiveLongitudinal consequences and potential interactions of COVID-19 and elite-level sports and exercise are unclear. Therefore, we determined the long-term detrimental cardiac effects of the interaction between SARS-CoV-2 infection and the...

Sacubitril/valsartan and arrhythmic burden in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis.

The aim of this study was to assess whether angiotensin receptor/neprilysin inhibitor (ARNI) decreases ventricular arrhythmic burden compared to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonist (ACE-I/ARB) treatment in chronic heart failure with reduced ejection fraction (HFrEF) patients. Further, we assessed if ARNI influenced the percentage of biventricular pacing. A systematic review of studies (both RCTs and observational studies) including HFrEF patients and those receiving ARNI after ACE-I/ARB treatment was conducted using Medline and Embase up to February 2023. Initial search found 617 articles. After duplicate removal and text check, 1 RCT and 3 non-RCTs with a total of 8837 patients were included in the final analysis. ARNI was associated with a significative reduction of ventricular arrhythmias both in RCT (RR 0.78 (95% CI 0.63-0.96); p = 0.02) and observational studies (RR 0.62; 95% CI 0.53-0.72; p < 0.001). Furthermore, in non-RCTs, ARNI also reduced sustained (RR 0.36 (95% CI 0.2-0.63); p < 0.001), non-sustained VT (RR 0.67 (95% CI 0.57-0.80; p = 0.007), ICD shock (RR 0.24 (95% CI 0.12-0.48; p < 0.001), and increased biventricular pacing (2.96% (95% CI 2.25-3.67), p < 0.001). In patients with chronic HFrEF, switching from ACE-I/ARB to ARNI treatment was associated with a consistent reduction of ventricular arrhythmic burden. This association could be related to a direct pharmacological effect of ARNI on cardiac remodeling.Trial registration: CRD42021257977.

Survival, ventricular arrhythmia, and implantable cardioverter-defibrillator usefulness in toxic cardiomyopathy due to substance abuse.

Toxic dilated cardiomyopathy (T-DCM) due to substance abuse is now recognized as a potential cause of severe left ventricular dysfunction. The burden of ventricular arrhythmias (VA) and the role of a prophylactic implantable cardioverter-defibrillator (ICD) are not well documented in this population. We aim to assess the usefulness of ICD implantation in a T-DCM cohort. Patients younger than 65 years with a left ventricular ejection fraction (LVEF)<35% followed at a tertiary center heart failure (HF) clinic between January 2003 and August 2019 were screened for inclusion. The diagnosis of T-DCM was confirmed after excluding other etiologies, and substance abuse was established according to the DSM-5 criteria. The composite primary endpoints were arrhythmic syncope, sudden cardiac death (SCD), or death of unknown cause. The secondary endpoints were the occurrence of sustained VA and/or appropriate therapies in ICD carriers. Thirty-eight patients were identified, and an ICD was implanted in 19 (50%) of these patients, only one for secondary prevention. The primary outcome was similar between the two groups (ICD vs. non-ICD; p=1.00). After a mean follow-up of 33±36 months, only two VA episodes were reported in the ICD group. Three patients received inappropriate ICD therapies. One ICD implantation was complicated with cardiac tamponade. Twenty-three patients (61%) had an LVEF ≥35% at 12 months. VA are infrequent in the T-DCM population. The prophylactic ICD benefit was not observed in our cohort. The ideal timing for potential prophylactic ICD implantation in this population needs further studies.

Role of dofetilide in patients with ventricular arrhythmias.

To assess effectiveness of dofetilide in reducing the burden of ventricular arrhythmias (VAs). Prior small sample studies show that dofetilide has benefit in reducing VA. However, large sample investigations with long-term follow-up are lacking. Two hundred seventeen consecutive patients admitted between January 2015 and December 2021 for dofetilide initiation for control of VA were assessed. Dofetilide was successfully started in 176 patients (81%) and had to be discontinued in the remaining 41 patients (19%). Dofetilide was initiated for control of ventricular tachycardia (VT) in 136 patients (77%), whereas 40 (23%) patients were initiated on dofetilide for reducing the burden of premature ventricular complexes (PVCs). The mean follow-up was 24 ± 7months. In total, among the 136 VT patients, 33 (24%) died, 11 (8%) received a left ventricular assist device (LVAD), and 3 (2%) received a heart transplant during follow-up. Dofetilide was discontinued in 117 (86%) patients due to lack of sustained effectiveness during follow-up. Dofetilide use was associated with similar odds of the composite outcome of all-cause mortality/LVAD/heart transplant (OR: 0.97, 0.55-4.23) in patients with ischemic cardiomyopathy (ICM) compared to those with non-ischemic cardiomyopathy (NICM). Dofetilide did not reduce PVC burden during follow-up in the 40 patients with PVCs (mean baseline PVC burden: 15%, at 1-year follow-up: 14%). Dofetilide use was less effective in reducing VA burden in our cohort of patients. Randomized controlled studies are needed to confirm our findings.

C70 WEARABLE CARDIOVERTER DEFIBRILLATOR IN LONG QT SYNDROME DURING PREGNANCY: TIME TO USE THE SHIELD

Abstract Introduction Long QT Syndrome (LQTS) is a rare cardiac channelopathy characterized by a high risk of lethal arrhythmias. Pregnancy and post–partum period may induce an increased vulnerability, so an appropriate prevention is needed. Case presentation A 31–year–old primigravid woman at 36 weeks of pregnancy was referred to our Cardiomyopathy Unit located in a tertiary centre for LQTS screening. The patient had a family history of LQTS (mother and brother) and Brugada syndrome (cousin). The 12–lead ECG (Figure 1) showed a long QT interval (QT corrected: 508 msec), while the transthoracic echocardiogram was unremarkable. The genetic test performed is still ongoing. The patient reported sporadic episodes of palpitations at rest and the following 24–hour ambulatory ECG revealed a very high burden of polymorphic ventricular arrhythmias, with about sixteen thousand premature ventricular complexes and a non–sustained ventricular tachycardia. Therefore, due to the patient’s high–risk for life–threatening arrhythmic events, metoprolol 25 mg o.d. was initiated and a wearable cardioverter defibrillator (WCD) with remote monitoring was provided during pregnancy and labour. After 3 weeks a caesarean delivery in epidural analgesia was performed and managed by a pregnancy heart team including a cardiologist, gynaecologist, obstetrician, and anaesthetist in close cardiac monitoring. No maternal or infant complications occurred, without arrhythmic episodes detected by the device. The WCD will be maintained also in the post–partum period with a narrow follow–up of the patient. Discussion In pregnant high–risk LQTS patients, beta–blockers are the first line therapeutic option, but they do not able to interrupt lethal arrythmias in out–of–hospital setting. The implantable cardiac defibrillator is not the best choice, due to the concerns about radiation exposure and anaesthesia during pregnancy. Moreover, lead–associated thrombosis and infections during pregnancy were reported in literature. The WCD is the ideal option in these cases. It is an external device suited for transient higher arrhythmic risk periods. Moreover, it allows a remote monitoring of arrhythmic burden (figure 2) which may help clinicians in guiding the follow–up and the therapeutic management of the patient. One drawback is the need of continuous patient’s compliance. Finally, a pregnancy heart team is mandatory in presence of these rare cardiac syndromes.