Symptomatic Ventricular Arrhythmias Research Articles

A 3-Dimensional Ablation At Patient With Tachycardia Right Ventricular Outflow Track (RVOT) Origin: First Experienced in Saiful Anwar General Hospital Malang

Background: Premature ventricular complexes (PVCs) occur commonly in general population. It can occur in patient without structural heart disease as well as those with any form of cardiac disease. Commonly PVCs are asymptomatic, but in patients with frequent PVCs causing palpitations, syncope or dizziness, easily to fatigue, or shortness of breath. PVCs has been connected with a more than two-fold higher risk of cardiovascular events including stroke, mortality and also associated with arrhythmias or cardiomyopathy. Medications can be used to suppress PVCs but when drug therapy is ineffective, PVC ablation is reasonable to eliminate symptoms and treat or prevent PVC-induced cardiomyopathy. Case Presentation: A hypertension and menopause, 57-year-old woman, frequently complained about palpitation with shortness of breath, dizziness and sometimes near syncope since 2017, occurring both at rest and with mild activities. After serial examinations, found Frequent PVC (39%) with RVOT-Origin and reduced ejection fraction (EF 48%), then conclude with Suspect Tachycardia Induced cardiomyopathies. She performs cardiac electrophysiological study and continue with 3-Dimentional Ablation with Radiofrequency (RFA) at RVOT in Saiful Anwar Hospital, that is The First 3-Dimension Ablation in East Java. 1 year follow up shows no recurrency and successful to improve quality of life of the patient Discussion: According to guideline, catheter ablation is class I recommendation for patients with symptomatic outflow tract ventricular arrhythmias if medications are ineffective, not tolerated, or patient’s choose Conclusion: Three-Dimensional Ablation at patient with Right Ventricular Outflow Track Tachycardia, can successfully eliminate PVCs with no recurrency in 1 year follow-up.

Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib

AbstractFirst-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been associated with an increased risk of cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this analysis, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N = 1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE). Among the 10 studies, most patients (median age, 67 years) were male (66.3%) and had CLL/SLL (60.5%). Overall incidence and exposure-adjusted incidence rates (EAIR) for atrial fibrillation, symptomatic ventricular arrhythmia, and hypertension were lower with zanubrutinib than ibrutinib. Despite a similar prevalence of preexisting cardiovascular events in ASPEN and ALPINE, atrial fibrillation/flutter incidence rates (6.1% vs 15.6%) and EAIR (0.2 vs 0.64 persons per 100 person-months; P < .0001) were lower with zanubrutinib than with ibrutinib. Symptomatic ventricular arrhythmia incidence was low for both zanubrutinib (0.7%) and ibrutinib (1.7%) with numerically lower EAIR (0.02 vs 0.06 persons per 100 person-months, respectively) for zanubrutinib. The hypertension EAIR was lower with zanubrutinib than ibrutinib in ASPEN but similar between treatment arms in ALPINE. The higher hypertension EAIR in ALPINE was inconsistent with other zanubrutinib studies. However, fewer discontinuations (1 vs 14) and deaths (0 vs 6) due to cardiac disorders occurred with zanubrutinib versus ibrutinib in ALPINE. These data support zanubrutinib as a treatment option with improved cardiovascular tolerability compared with ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. These trials were registered at www.ClinicalTrials.gov as # NCT03053440, NCT03336333, NCT03734016, NCT04170283, NCT03206918, NCT03206970, NCT03332173, NCT03846427, NCT02343120, and NCT03189524.

Mid-term outcome of catheter ablation of idiopathic non-outflow tract ventricular arrhythmias

BackgroundCatheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs.Method and ResultsFrom 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546).ConclusionDespite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

Long-term outcomes of patients with ventricular arrhythmias and negative programmed ventricular stimulation followed with implantable loop recorders: Impact of delayed-enhancement cardiac magnetic resonance imaging.

Programed ventricular stimulation (PVS) is a risk stratification tool in patients at risk for adverse arrhythmia outcomes. Patients with negative PVS may yet be at risk for adverse arrhythmia-related events, particularly in the presence of symptomatic ventricular arrhythmias (VA). To investigate the long-term outcomes of real-world patients with symptomatic VA without indication for device therapy and negative PVS, and to examine the role of cardiac scaring on arrhythmia recurrence. Patients with symptomatic VA, and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR), and negative PVS testing were included. All patients underwent placement of implantable cardiac monitors (ICM). Survival analysis was performed to investigate the impact of LGE-CMR findings on survival free from adverse arrhythmic events. Seventy-eight patients were included (age 60 ± 14 years, women n = 36 (46%), ejection fraction 57 ± 9%, cardiomyopathy n = 26 (33%), mitral valve prolapse [MVP] n = 9 (12%), positive LGE-CMR scar n = 49 (62%), history of syncope n = 23 (29%))including patients with primarily premature ventricular contractions (n = 21) or nonsustained VA (n = 57). Patients were followed for 1.6 ± 1.5 years during which 14 patients (18%) experienced VA requiring treatment (n = 14) or syncope due to bradycardia (n = 2). Four/9 patients (44%) with MVP experienced VA (n = 3) or syncope (n = 1). Baseline characteristics between those with and without adverse events were similar (p > 0.05); however, the presence of cardiac scar on LGE-CMR was independently associated with an increased risk of adverse events (hazard ratio: 5.6 95% confidence interval:[1.2-27], p = 0.03, log-rank p = 0.03). In a real-world cohort with long-term follow-up, adverse arrhythmic outcomes occurred in 18% of patients with symptomatic VA despite negative PVS, and this risk was significantly greater in patients with positive DE-CMR scar. Long term-monitoring, including the use of ICM, may be appropriate in these patients.

Disease progression in exercise-induced compared to desmosomal arrhythmogenic cardiomyopathy - a longitudinal cohort study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital, Procardio Center for Innovation Introduction Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease caused by mutations in genes encoding the cardiac desmosomes, while exercise-induced AC (EiAC) has been proposed as an acquired similar phenotype in athletes. Little is known about the progression of EiAC compared to AC. Purpose To assess functional and structural disease progression in EiAC compared to desmosomal AC during long-term follow-up. Methods We consecutively included probands with definite AC diagnosis according to the 2010 Task Force Criteria and patients with EiAC in a longitudinal cohort study. EiAC was diagnosed in competitive endurance athletes (&amp;gt;24 MET-hours/week for &amp;gt;6 consecutive years) referred with symptomatic ventricular arrhythmias who had no family history, no genetic mutations associated with heart disease, and no other identified etiology after through clinical work-up. All patients in both groups were recommended to avoid high intensity exercise. Progression of the structural phenotype was assessed by regular repeated echocardiographic examinations during long-term follow-up. Right ventricular (RV) function and size were assessed by RV fractional area change (FAC), RV basal diameter (RVD) and RV outflow tract (RVOT) diameter. Disease progression was evaluated and compared using linear mixed model regression. Results Forty-one EiAC patients (15% women, age 45±13 years) and 84 AC probands (51% mutation positive, 35% women, age 43±15) were followed for 6.6 (IQR 3.7-10.5) and 7.9 (IQR 5.2-10.8) years, respectively. Key parameters from 570 echocardiographic examinations (184 EiAC and 386 AC) were assessed. There was no deterioration of RV function during follow-up in EiAC patients, in contrast to AC patients (FAC yearly progression rate: EiAC +0.02% [95% CI -0.27 to 0.31] vs AC -0.60% [95% CI -0.71 to -0.50] per year, p=0.001, Figure left panel). RV size did not increase in EiAC patients in contrast to AC patients (RVD: EiAC +0.01 mm [95% CI -0.00 to 0.03] vs AC +0.78 mm [95% CI 0.68 to 0.89] per year, p&amp;lt;0.001, Figure mid panel, and RVOT: EiAC +0.01 mm [95% CI -0.01 to 0.02] vs AC +0.47 mm [95% CI 0.38 to 0.56] per year, p&amp;lt;0.001, Figure right panel). Conclusion Patients with exercise-induced AC had no evidence of disease progression during long-term follow-up. These patients had a more benign disease trajectory than patients with desmosomal AC. Despite the limited sample size, these results seem reassuring for patients diagnosed with exercise-induced AC.

Value of implant-based telemonitoring in the high-risk population of ventricular assist device patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Telemonitoring of heart failure (HF) patients is an evolving field. Prior studies presented promising results. However, the relevance of telemonitoring in the specific cohort of end-stage HF patients on ventricular assist device (VAD) therapy has not been analysed yet. Purpose This study aimed to evaluate the benefit of daily implant-based multiparameter-telemonitoring in high-risk HF-patients on VAD therapy with an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization defibrillator (CRT-D) including telemonitoring function. Beyond that, patients’ outcome and complication rates were evaluated. Methods A total of 30 end-stage HF-patients (65 ± 10 years, 89 % male) with a VAD and an ICD or a CRT-D with telemonitoring function were included in this observational single center study. Long-term follow-up data (4.28 ± 2.62 years) were assessed. Results All patients (n=30, 100%) received daily ICD or CRT-D telemonitoring. In the majority of patients (73%, n=22) the telemedical center had to take actions a mean of 3 times. Most events (84%, n=45) were identified within 24 hours. An acute alert due to sustained ventricular arrhythmias (VAs) occurred in 13 patients (65%) with 46% of them (n=6) requiring a shock delivery. Eight patients (62%) were hospitalized due to symptomatic VAs. Inadequate shocks were recognized in 3 patients (23%). In 12 patients (92%) immediate medication adjustments were recommended. Relevant lead problems were revealed in 13 patients (43%) with 6 patients (46%) undergoing consecutive lead revisions. Device-reprogramming was recommended in 50% of all VAD-patients (n=15). Compared to HF-patients without remote monitoring, daily telemonitoring significantly reduced the number of in-hospital device controls by 44% (p&amp;lt;0.01). Conclusions Daily implant-based-telemonitoring increased patient safety as it allowed for pre-emptive interventions and an immediate detection of cardiac arrhythmias and device/lead problems. Even in this high-risk HF-patient population, telemonitoring significantly reduced the number of in-hospital device-controls. Further studies are warranted to confirm these initial observations.

Multi-day telemonitoring is the optimum control method in the medicational treatment of arrhythmias

Background. The use of antiarrhythmic (AA) drugs requires constant monitoring due to the risk of arrhythmic and side effects. It is impossible to quickly identify and respond to emerging adverse events using 24-hour monitoring of the electrocardiogram (ECG), due to the method technical features. The introduction into practice of multi-day telemonitoring (MTM) of ECG contributes to an increase in the detection of rare and asymptomatic arrhythmias, and improves control over the AA therapy effectiveness.Objective. To study the possibilities and advantages of MTM in the selection of AA therapy and the prevention of its complications in patients with ventricular arrhythmias (VA).Design and methods. The study included 73 patients with frequent symptomatic high-grade VA (44 women and 29 men) aged 28 to 86 years (56.6 ± 28.3 years), in whom MTM ECG was performed for the purpose of individual selection of AA therapy.Results. In 19 % patients using MTM, the psychogenic nature of VA and a necessity to avoid prescribing was suspected. In 63 % patients with VA the optimal AA therapy in the minimum effective doses was selected using MTM, in 18 % patients the futility of drug therapy was proven and radiofrequency ablation was recommended.Conclusion. MTM ECG is justified for the selecting AA therapy in patients with VA. MTM has undoubted advantages over daily monitoring and helps to reduce the time for AA agent choosing.

ESC-Leitlinie 2022: Management ventrikulärer Arrhythmien in der klinischen Praxis

The recently published guideline of the European Society of Cardiology for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death updates the guideline from 2015. Overall, the current guideline is characterised by a great practical relevance: Illustrative algorithms, e.g., for diagnostic evaluation, and tables make the guideline a user-friendly reference book. In the diagnostic evaluation and risk stratification of sudden cardiac death, cardiac magnetic resonance imaging and genetic testing are significantly upgraded. In long-term management, the optimal treatment of the underlying disease is essential, and recommendations for heart failure therapy are adapted to current international guidelines. Catheter ablation is upgraded especially for patients with ischaemic cardiomyopathy and recurrent ventricular tachycardia, as well as in the management of symptomatic idiopathic ventricular arrhythmias. Criteria for primary prophylactic defibrillator therapy remain controversial. In the context of dilated cardiomyopathy, imaging, genetic testing, and clinical factors are given special weight in addition to left ventricular function. Additionally, revised diagnostic criteria for a large number of primary electrical diseases are provided.

Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure

BackgroundMesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF). ObjectivesThis study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF. MethodsThis randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity. ResultsThe primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L). ConclusionsThe primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.

The Role of Daily Implant-Based Multiparametric Telemonitoring in Patients with a Ventricular Assist Device.

The telemonitoring of heart failure (HF) patients is becoming increasingly important. This study aimed to evaluate the benefit of telemonitoring in end-stage HF patients with a ventricular-assistance device (VAD). A total of 26 HF-patients (66 ± 11 years, 88% male) on VAD therapy with an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization defibrillator (CRT-D) including telemonitoring function were enrolled. The long-term follow-up data (4.10 ± 2.58 years) were assessed. All the patients (n = 26, 100%) received daily ICD/CRT-D telemonitoring. In most of the patients (73%, n = 19), the telemedical center had to take action for a mean of three times. An acute alert due to sustained ventricular arrhythmias (VAs) occurred in 12 patients (63%) with 50% of them (n = 6) requiring ICD shock delivery. Eight patients (67%) were hospitalized due to symptomatic VAs. In 11 patients (92%), immediate medication adjustments were recommended. Relevant lead issues were revealed in thirteen patients (50%), with six patients (46%) undergoing consecutive lead revisions. Most of the events (83%) were detected within 24 h. Daily telemonitoring significantly reduced the number of in-hospital device controls by 44% (p &lt; 0.01). The telemonitoring ensured that cardiac arrhythmias and device/lead problems were identified early, allowing pre-emptive and prompt interventions. In addition, the telemonitoring significantly reduced the number of in-hospital device controls in this cohort of HF patients.

Post-ablation augmentation of skin sympathetic nerve activity predicts a poor outcome of idiopathic ventricular arrhythmias

BackgroundThe neuromodulation effect after ventricular arrhythmia (VA) ablation is unclear. The study aimed to investigate skin sympathetic nerve activity (SKNA) changes in patients receiving catheter ablations for idiopathic VA. MethodsOf 43 patients with drug-refractory symptomatic VA receiving ablation, SKNA was continuously recorded for 10 min during resting from electrocardiogram lead I configuration and bipolar electrodes on the right arm 1 day before and 1 day after ablation. ResultsTwenty-two patients with acute procedure success and no recurrence during follow-ups were classified as sustained success group (group 1). Other 21 patients were classified as failed ablation group (group 2). Baseline SKNA showed no significant difference between the two groups. Post-ablation SKNA in group 2 was significantly higher than in group 1. In patients with ablation involved right ventricular outflow tract (RVOT), the post-ablation SKNA was also significantly higher in group 2. In contrast, there was no difference in post-ablation SKNA between groups in patients receiving non-RVOT ablation. ConclusionThe neuromodulation response after RVOT ablation may correspond to the sympathetic nerve distribution at RVOT. Augmentation of sympathetic activity after VA ablation indicates an unsuccessful VA suppression, especially in patients receiving ablation of RVOT VA.

A Four-Stepwise Electrocardiographic Algorithm for Differentiation of Ventricular Arrhythmias Originated from Left Ventricular Outflow Tract.

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL &gt; 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II &gt; 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II &lt; 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR &gt; 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

Common genetic variants improve risk stratification after the atrial switch operation for transposition of the great arteries

BackgroundClinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical course remains. We studied whether common genetic variants are associated with outcome and add value to a clinical risk score in TGA-AtrSO patients. Methods and resultsThis multicenter study followed 133 TGA-AtrSO patients (aged 28 [IQR 24–35] years) for 13 (IQR 9–16) years and examined the association of genome-wide single-nucleotide polymorphisms (SNPs) with a composite endpoint of symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one genome-wide significant (p < 1 × 10−8) locus and 18 suggestive loci (p < 1 × 10−5). A genetic risk score constructed on the basis of independent SNPs with p < 1 × 10−5 was associated with outcome after correction for the clinical risk score (HR = 1.26/point increase [95%CI 1.17–1.35]). Risk stratification improved with a combined risk score (clinical score + genetic score) compared to the clinical score alone (p = 2 × 10−16, C-statistic 0.95 vs 0.85). In 51 patients with a clinical intermediate (5–20%) 5-year risk of events, the combined score reclassified 32 patients to low (<5%) and 5 to high (>20%) risk. Stratified by the combined score, observed 5-year event-free survival was 100%, 79% and 31% for low, intermediate, and high-risk patients, respectively. ConclusionsCommon genetic variants may explain some variation in the clinical course in TGA-AtrSO and improve risk stratification over clinical factors alone, especially in patients at intermediate clinical risk. These findings support the hypothesis that including genetic variants in risk assessment may be beneficial.

Hybrid-Approach Ablation in Drug-Refractory Arrhythmogenic Right Ventricular Cardiomyopathy

Management of ventricular arrhythmias (VAs) beyond implantable cardioverter-defibrillator positioning in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging. Catheter ablation of the ventricular substrate often requires a combination of endocardial and epicardial approaches, with disappointing outcomes due to the progressive nature of the disease. We report the Universitair Ziekenhuis Brussel experience through a case series of 16 patients with drug-refractory ARVC, who have undergone endocardial and/or epicardial catheter ablation of VAs with a thoracoscopic hybrid-approach. After a mean follow-up time of 5.16 years (SD 2.9 years) from the first hybrid-approach ablation, VA recurrence was observed in 5 patients (31.25%): among these, patients 4 patients (80%) received a previous ablation and 1 of 11 patients (9.09%) who had a hybrid ablation as first approach had a VA recurrence (80% vs 9.09%; log-rank p=0.04). Despite the recurrence rate of arrhythmic events, all patients had a significant reduction in the arrhythmic burden after ablation, with a mean of 4.65 years (SD 2.9 years) of freedom from clinically significant arrhythmias, defined as symptomatic VAs or implantable cardioverter-defibrillator-delivered therapies. In conclusion, our case series confirms that management of VAs in patients with ARVC is difficult because patients do not always respond to antiarrhythmic medications and can require multiple invasive procedures. A multidisciplinary approach involving cardiologists, cardiac surgeons, and cardiac electrophysiologists, together with recent cardiac mapping techniques and ablation tools, might mitigate these difficulties and improve outcomes.

The Utility of Surgical Cardiac Sympathetic Denervation in the Management of Ventricular Arrhythmias for all Etiologies: A Systematic Review

Background: The antiadrenergic and antifibrillatory effects of cardiac sympathectomy in pathological states such as long QT syndrome are well established. The indications for the procedure have expanded since the videoassisted thoracoscopic approach was first used. However, the procedure is currently largely used in cases where medication has failed to prevent recurrence of symptomatic ventricular arrhythmia, or in cases of medication intolerance, and large randomised controlled trials are thus non-existent in the literature. The aim of this study was to perform a systematic review of the available literature to examine the utility of cardiac denervation in the management of all ventricular arrhythmias. Methods: A total of 17 studies published between 2009 and 2019 were evaluated for bias using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. In addition the Harbour and Miller Grading System (2001) was used to assess the significance of the evidence in this review. Results: All studies demonstrated a protective effect of sympathectomy against ventricular arrhythmias in both primary and secondary prevention strategies. The following risk of bias was observed: low in 5 studies, moderate in 8 studies, and serious risk in 4 studies. The highest level of evidence observed was 2++ in 3 studies. Conclusion: Cardiac sympathetic denervation provides benefit for patients with ventricular arrhythmias, in cases of refractory disease or in patients who require a primary prevention strategy where first-line therapies are not tolerated.

Long-term outcomes of non-contact multi-electrode balloon catheter mapping-guided ablation of ventricular arrhythmias originating from the outflow tract

IntroductionThe outflow tract (OT) regions of the ventricles are a common location of origin for idiopathic ventricular arrhythmias (VA). Non-contact mapping (NCM) with a multi-electrode balloon catheter Ensite-Array enables three-dimensional reconstruction of the geometry of the cardiac chambers and accurate mapping of the propagation map, based on a single beat analysis, facilitating the ablation and contributing procedure success. ObjectiveAssessment of the feasibility and long-term outcomes following NCM-guided OT VA ablation. MethodsSingle center retrospective analysis of patients admitted for symptomatic OT VA ablation. Demographic and clinical characteristics of patients, procedure data and long-term outcomes were assessed. ResultsFifty-eight patients (79.3% female, age 43.9±17.6 years) were considered, 89.7% without structural heart disease. In 85.7% of the cases left ventricle ejection fraction (LVEF) was preserved (LVEF≥50%), 8.6% had mild systolic dysfunction (LVEF 40%-49%) and 5.7% had moderate systolic dysfunction (LVEF 30%-39%). Twenty-four-hour Holter recording documented sustained VA episodes in 12.1% of the patients, non-sustained VA in 31.0%, and >10 000 premature ventricular complex (PVC)/24 h in 56.9%, with an ECG suggesting right ventricular OT origin in 84.5%. There was total elimination of PVC in 87.9% cases and a significant reduction in 3.4%. During a mean follow-up of 5.5 years, 87.9% patients remained asymptomatic without medication, 12.1% underwent re-ablation due to symptomatic PVC recurrence, and two cases underwent a third successful intervention. ConclusionNon-contact mapping-guided multi-electrode balloon catheter VA ablation is a highly effective and safe procedure, with a low rate of long-term recurrence.

Common genetic variants improve risk stratification after atrial switch operation for transposition of the great arteries

Abstract Background Current clinical risk scores are able to predict late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but a large heterogeneity in clinical course remains. Purpose To study whether common genetic factors are predictive of outcome and provide added value to an existing clinical risk score in TGA-AtrSO patients. Methods This multicenter study examined the association of genome-wide single-nucleotide polymorphisms (SNPs) in TGA-AtrSO patients with a combined clinical endpoint: time to symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Furthermore, we evaluated whether a polygenic risk score (PRS) constructed of independent single-nucleotide polymorphisms (SNPs) with a p&amp;lt;1x10–5 could be of added value to a recently published clinical risk score (included clinical factors: age &amp;gt;30 years, prior ventricular arrhythmia, age &amp;gt;1 year at repair, ≥moderate right ventricular dysfunction, severe tricuspid regurgitation, and ≥mild left ventricular dysfunction). Results We followed 133 patients (age at inclusion 28 [IQR 24–35] years, 59% male) for 13 [IQR 8–16] years. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one locus that reached genome-wide significance (p&amp;lt;1x10–8) and 18 loci marked by 20 SNPs that reached the suggestive threshold (p&amp;lt;1x10–5). The constructed PRS remained an independent predictor after correction for the clinical score (HR=1.21/point increase [95% CI 1.13–1.29], p=3x10–10). While the clinical risk score indicated intermediate (5–20%) 5-year risk of events in 52 patients (39%), the combined risk score (clinical score + PRS) reclassified 35 patients to low (&amp;lt;5%) and 6 to high (&amp;gt;20%) risk. Observed 5-year event-free survival based on the combined score remained 100% for low-risk patients, compared to 23% and 64% in intermediate and high-risk patients, respectively. This resulted in improved risk stratification with the combined risk score vs the clinical risk score alone (p=2x10–16, C-statistic 0.95 vs 0.85). Conclusions Genetic factors explain some of the variation in clinical course of TGA-AtrSO patients and improve risk stratification. In the heterogeneous group of patients with a clinical score indicating intermediate risk, the combined model could classify 67% of patients more accurately to &amp;lt;5% or &amp;gt;20% risk. These data argue for more research into the impact of genetics on clinical outcome in adult congenital heart disease. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation Figure 1. Risk stratification of predicted 5-year risk of events based on the clinical model versus the combined model (clinical risk score + polygenic risk score).

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Safety and efficacy of flecainide associated with beta-blockers in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy associated with a high risk of ventricular arrhythmia (VA). Current guidelines recommend beta-blockers as first-line medical therapy and if ineffective, sotalol or amiodarone. We describe our experience, as a tertiary centre for ARVC, with the effectiveness and tolerance of flecainide in addition to beta-blockers to prevent VA in ARVC. We retrospectively included 100 consecutive ARVC patients who received flecainide with beta-blockers between May 1999 and November 2017. Treatment persistence and related side effects were assessed, as was VA-free survival on treatment, 24-h Holter monitoring and programmed ventricular stimulation (PVS) off- and on-treatment. Tolerance was good, with 10% flecainide discontinuations (lack of efficacy in six, atrial fibrillation in one, and side effects in three). No Brugada-induced electrocardiography pattern on flecainide or haemodynamic impairment was reported. Premature ventricular contraction burden at 24-h Holter monitoring was significantly decreased under treatment [median 415 (interquartile range, IQR 97-730) vs. 2370 (1572-3400) at baseline, P < 0.0001, n = 46]. Among the 33 patients with PVS under treatment, PVS was positive in 40% on-treatment vs. 94% off-treatment (P < 0.001). During a median follow-up of 47 months (IQR 23-73), 22 patients presented sustained VA on treatment, corresponding to an event rate of 5% [95% confidence interval (CI) (0.6-9)] at 1 year and 25% [95% CI (14-35)] at 5 years under treatment. No patient died. This study suggests that flecainide and beta-blockers association is complementary to implantable cardioverter-defibrillator and catheter ablation and is safe for treating persistent symptomatic VA in patients with ARVC.

Safety and efficacy of flecainide associated with beta-blockers in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibro-fatty replacement of cardiomyocytes and associated with a high risk of ventricular arrhythmia (VA). Current guidelines recommend beta-blockers as first-line medical therapy and if ineffective, sotalol or amiodarone. To describe our experience, as a tertiary center for ARVC, with the effectiveness and tolerance of flecainide in addition to beta-blockers to prevent VA in ARVC. We retrospectively included 100 consecutive ARVC patients who received flecainide with beta-blockers between May 1999 and November 2017. Treatment persistence and related side effects were assessed, as was VA-free survival on treatment, 24-hr Holter monitoring and programmed ventricular stimulation (PVS) off- and on-treatment. Tolerance was good, with 10% flecainide discontinuations (lack of efficacy in 6, atrial fibrillation in one and side effects in 3). No Brugada-induced electrocardiography pattern on flecainide or hemodynamic impairment was reported. Premature ventricular contraction burden at 24-hr Holter monitoring was significantly decreased under treatment (median 415 [interquartile range 97–730] vs. 2370 [1572–3400] at baseline, P < 0.0001, n = 46). Among the 33 patients with PVS under treatment, PVS was positive in 40% on-treatment versus 94% off-treatment ( P < 0.001). During a median follow-up of 47 months (interquartile range 23–73), 22 patients presented sustained VA on treatment, corresponding to an event rate of 5% (95% confidence interval [0.6–9]) at 1 year and 25% (95% confidence interval [14–35]) at 5 years under treatment ( Fig. 1 ). No patient died. This study suggests that flecainide and beta-blockers association is complementary to ICD and catheter ablation and is safe for treating persistent symptomatic VA in patients with ARVC.