Reduction Of Ventricular Arrhythmias Research Articles

C-36 | Association between coronary revascularization and reduction in ventricular arrhythmias in stable coronary artery disease patients: A systematic review and meta-analysis

C-36 | Association between coronary revascularization and reduction in ventricular arrhythmias in stable coronary artery disease patients: A systematic review and meta-analysis

Long-term efficacy and safety of cardiac genome editing for catecholaminergic polymorphic ventricular tachycardia.

Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model. The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for Ryr2 variant p.Arg176Gln (R176Q/+). Guide RNA and SaCas9 were delivered using AAV9 vectors injected subcutaneously in 10-day-old mice. At 6 weeks after injection, R176Q/+ mice had a 100% reduction in ventricular arrhythmias compared to controls. When aged to 12 months, injected R176Q/+ mice maintained a 100% reduction in arrhythmia induction. Deep RNA sequencing revealed the formation of insertions/deletions at the target site with minimal off-target editing on the wild-type allele. Consequently, CRISPR/SaCas9 editing resulted in a 45% reduction of total Ryr2 mRNA and a 38% reduction in RyR2 protein. Genome editing was well tolerated based on serial echocardiography, revealing unaltered cardiac function and structure up to 12 months after AAV9 injection. Taken together, AAV9-mediated CRISPR/Cas9 genome editing could efficiently disrupt the mutant Ryr2 allele, preventing lethal arrhythmias while preserving normal cardiac function in the R176Q/+ mouse model of CPVT.

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.

PO-04-223 ASSOCIATION BETWEEN ANTIPARASITIC TREATMENT AND VENTRICULAR ARRYTHMIAS IN PATIENTS WITH CHAGAS DISEASE

Benznidazole and Nifurtimox are the two currently available antiparasitic treatments available for Chagas disease (CD), an important cause of cardiomyopathy and arrhythmias. There are limited data available describing impact of antiparasitic treatment on arrhythmia outcomes. Compare the incidence of ventricular arrhythmias in Chagas patients treated with anti-parasitic medication versus those who did not receive treatment. Patients treated at a Chagas disease center of excellence were retrospectively analyzed for ambulatory rhythm monitoring data (Holter and 14-day patch monitor). Patients with implantable cardiac devices were excluded. Significant ventricular arrhythmias were defined as either a PVC burden >/=1% or non-sustained ventricular tachycardia (NSVT) ≥4 beats. Patients were analyzed based on CD treatment: Benznidazole, Nifurtimox, or no treatment. Patients with incomplete treatment courses were excluded from analysis. A Fisher exact test was used to compare categorical variables. There were 191 patients with CD between 12/2014 and 8/2022 available for analysis, of whom 66 patients underwent ambulatory rhythm monitoring. Of these, 20 were male and 46 were female with an average age of 55.3 ± 12.6 years, and ejection fraction of 56.7 ± 10.5%. Of the 66 patients, 42 (63.6%) received treatment, 22 (33.3%) had no treatment, and 2 (3.0%) received incomplete treatment for CD. Among patients that received treatment for CD, 11/42 (26.2%) had significant ventricular arrhythmias on ambulatory rhythm monitoring. In comparison, among patients who did not receive CD treatment, 12/22 (54.5%) had significant ventricular arrhythmias (p = 0.031). No significant difference in the number of ventricular arrhythmias was observed between the Benznidazole (7/29, 24.1%) and Nifurtimox (4/12, 33.3%) treatment groups. These data demonstrate that treatment of CD is associated with a reduction in ventricular arrhythmias on ambulatory rhythm monitoring. Further studies are needed to determine if CD treatment can lead to reduced incidence of sudden death.

PO-04-232 PERCUTANEOUS STELLATE GANGLION BLOCKADE FOR ELECTRICAL STORM: LARGE SINGLE CENTRE EXPERIENCE

Electrical storm (ES) is defined as three or more episodes of ventricular arrhythmia requiring defibrilltaion or anti tachycardia pacing within a day.Some times electrical storm may not respond to anti-arrhythmic drugs alone.Increased sympathetic activity plays significant role in electrical storm.Stellate ganglion blockade reduces sympathetic activity and helpful in reduction of ventricular arrhythmias. We aimed to study the effectiveness and outcomes of percutaneous stellate ganglion blockade (SGB) in the patients with drug-refractory electrical storm. The study included patients with a drug-refractory electrical storm. Before giving SGB, at least two anti-arrhythmic drugs(AAD) were given before SGB. Bupivacaine was injected in the vicinity of the stellate ganglion under Ultrasound quidance. A total of 83 procedures were performed on 56 patients (71% males, 60+6 years).Fourty three patients (76%) had ischemic heart disease. Nearly 66%(37/56) of patients were free from ventricular arrhythmias(VA) at 24 hours after left SGB and 51%(29/56) were arrhythmia free at 72 hours. Bilateral SGB was done in 16 patients who had failed left-sided SGB with a success rate of 36%. Heart failure and shock were documented in 65% and 55% respectively. Twenty Five (44%) patients were on both Intra-aortic balloon counterpulsation and inotrope support. All-cause mortality was 32% (18/56). Cardiovascular mortality was 28% (16/56). Septic shock in one patient and Ischemic brain stroke was the cause of death in the other patient. VA recurrence, poor left ventricular ejection fraction, and failed stellate ganglion blockade were associated with increased mortality. Procedure-related complications like transient bradycardia(16%), hematoma(14%), hoarseness of voice (10%), persistent ptosis(5%), and monoparesis(3.5%) were noted, all of which were resolved within two weeks of post-procedure. SGB helps to stabilize the hemodynamic status of the patients with electrical storm. It also provides time for

110 ANEURYSMECTOMY AND SURGICAL ABLATION: WHEN?

Abstract A 60-year-old man with a previous myocardial infarction was admitted to our ICU for acute pulmonary edema in the context of an acute antero-lateral non-ST elevation myocardial infarction. Echocardiography showed severe left ventricular (LV) dilatation with extensive wall motion abnormalities, large apical aneurysm and severe systolic dysfunction. Coronary angiography showed a triple-vessel disease with proximal occlusion of the left anterior descending artery. During the hospitalization, multiple episodes of drug-resistant monomorphic ventricular tachycardias occurred, requiring repeated DC Shock. After Heart Team discussion, the patient underwent coronary artery bypass grafting, LV restoration according to the procedure described by Guilmet and surgical cryoablation. The Guilmet septoexclusion is indicated when the interventricular septum is more involved than the free wall. After aneurysm incision, cryolesions were applied at the septum and at the transitional zone of the scar and viable tissue. Thus, the anterior free wall was sewn obliquely to the septum. Finally, the edges of the incision, anterior and septal, were sewn together to assure a definitive hemostasis (overcoat technique). After surgery, an implantable cardioverter-defibrillator was implanted in secondary prevention. The postoperative course and subsequent cardiological follow-up were characterized by a gradual clinical improvement with mild increasing in LV function and reduction in ventricular arrhythmias. Nowadays, combined aneurysmectomy and endocardial ablation are rarely performed, but should be considered in patients with LV aneurysm who manifest drug-resistant ventricular arrhythmias. Encircling cryoablation in a remodelled ventricle is safe and effective in reducing ventricular arrhythmias which are a negative prognostic factor.

1134 IN-HOSPITAL ARRHYTHMIC BURDEN REDUCTION IN DIABETIC PATIENTS WITH ACUTE MYOCARDIAL INFARCTION TREATED WITH SGLT2-INHIBITORS: INSIGHTS FROM THE SGLT2-I AMI PROTECT STUDY

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients. Objectives To investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users). Methods Patients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization. Results The study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-I users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs.15.7%, p=0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR=0.35; 95%CI 0.14–0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-I therapy remained an independent predictor of VT/VF occurrence (OR=0.20; 95%CI 0.04–0.97; p = 0.046) but not of AF occurrence. Conclusions In T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control. Trial registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867.

Neuromodulation for the Treatment of Refractory Ventricular Arrhythmias

BackgroundNeuromodulation is increasingly recognized as a therapeutic strategy for patients with refractory ventricular arrhythmias (VAs). Percutaneous stellate ganglion blockade (SGB), transcutaneous magnetic stimulation (TcMS), and surgical cardiac sympathetic denervation (CSD) have all been utilized in this setting. ObjectivesThis study sought to characterize contemporary use and outcomes of these neuromodulation techniques for patients with refractory VA. MethodsThis retrospective cohort study included all patients at the Hospital of the University of Pennsylvania with antiarrhythmic drug (AAD)-refractory VA from 2019 to 2021 who were treated with SGB, TcMS, or CSD. ResultsA total of 34 patients (age 61 ± 14 years, 15 polymorphic VAs [44%], refractory to 1.8 ± 0.8 AADs) met inclusion criteria. SGB was performed on 11 patients (32%), TcMS on 19 (56%), and CSD on 7 (21%). Neuromodulation was associated with a reduction in the number of episodes of sustained VAs from 7 [IQR: 4-12] episodes in the 24 hours before the initial neuromodulation strategy to 0 [IQR: 0-1] episodes in the subsequent 24 hours (P < 0.001). During 1.2 ± 1.1 years of follow-up, 21 (62%) experienced recurrent VAs, and among those patients, the median time to recurrence was 3 [IQR: 1-25] days. Outcomes were similar among patients with monomorphic and polymorphic VAs. Among patients who had an acute myocardial infarction within 30 days before neuromodulation, the burden of VAs decreased from 11 [IQR: 7-12] episodes to 0 episodes in the 24 hours after treatment. ConclusionsAutonomic neuromodulation with SGB, TcMS, or CSD in patients with AAD-refractory VAs is safe and results in substantial acute reduction of VA although recurrent arrhythmias are common, and not all patients experience a reduction in arrhythmia burden.

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

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

In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study.

BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients.ObjectivesTo investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).MethodsPatients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non-SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization.ResultsThe study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-i users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs. 15.7%, p = 0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR = 0.35; 95%CI 0.14–0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-i therapy remained an independent predictor of VT/VF occurrence (OR = 0.20; 95%CI 0.04–0.97; p = 0.046) but not of AF occurrence.ConclusionsIn T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control.Trial registrationData are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov, identifier: NCT05261867.

A narrative review on sacubitril/valsartan and ventricular arrhythmias.

Sacubitril/valsartan, the first angiotensin receptor neprilysin inhibitor approved by the Food and Drug Administration for marketing, has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in patients with chronic heart failure with a reduced ejection fraction. However, some researchers have also found that sacubitril/valsartan has an antiarrhythmic effect. The mechanism by which sacubitril/valsartan reduces the mortality associated with malignant ventricular arrhythmias is not precise. Many studies have concluded that ventricular arrhythmia is associated with a reduction in myocardial fibrosis. This article reviews the current understanding of the effects of sacubitril/valsartan on the reduction of ventricular arrhythmia and explains its possible mechanisms. The results of this study suggest that sacubitril/valsartan reduces the occurrence of appropriate implantable cardioverter-defibrillator shocks. Meanwhile, sacubitril/valsartan may reduce the occurrence of ventricular arrhythmias by affecting 3 pathways of B-type natriuretic peptide, Angiotensin II, and Bradykinin. The conclusion of this study is that sacubitril/valsartan reduces the number of implantable cardioverter-defibrillator shocks and ventricular arrhythmias in heart failure with reduced ejection fraction patients.

HF-567-02 SACUBITRIL-VALSARTAN AND BURDEN OF VENTRICULAR ARRHYTHMIA: A META-ANALYSIS

PARADIGM-HF showed a reduction in sudden cardiac death with Sacubitril-Valsartan (SV) use compared to enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, it is not clear if there is significant reduction in ventricular arrhythmias due to SV.

Impact of Percutaneous Mitral Valve Repair Using the MitraClipTM System on Ventricular Arrhythmias and ICD Therapies.

Transcatheter edge-to-edge repair (TEER) using the MitraClip™ device has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high or prohibitive surgical risk. Only limited information regarding the impact of TEER on ventricular arrhythmias (VA) has been reported. The aim of the present study was to assess the impact of TEER using the MitraClipTM device on the burden of VA and ICD (Implantable Cardioverter Defibrillator) therapies. Among 600 MitraClipTM implantations performed in our clinic between September 2009 and October 2018, we identified 86 patients with successful TEER and an active implantable cardiac device (pacemaker, ICD, CRT-P/D (Cardiac Resynchronization Therapy-Pacemaker/Defibrillator)) eligible for retrospective VA analyses. These patients presented with mainly functional MR (81.4%) and severely reduced left ventricular ejection fraction (mean LVEF 22.1% ± 10.3%). The observation period comprised 456 ± 313 days before and 424 ± 287 days after TEER. The burden of ventricular arrhythmias (sustained ventricular tachycardia (sVT) and ventricular fibrillation (VF)) was significantly reduced after TEER (0.85 ± 3.47 vs. 0.43 ± 2.03 events per patient per month, p = 0.01). Furthermore, the rate of ICD therapies (anti-tachycardia pacing (ATP) and ICD shock) decreased significantly after MitraClipTM implantation (1.0 ± 3.87 vs. 0.32 ± 1.41, p = 0.014). However, reduction of VA burden did not result in improved two-year survival in this patient cohort with severely reduced LVEF. Mitral valve TEER using the MitraClip™ device was associated with a significant reduction of ventricular arrhythmias and ICD therapies.

The effect of statins on RyR and RyR-associated disease.

We sought to review the effects of statins on the ryanodine receptor (RyR) and on RyR-associated diseases, with an emphasis on catecholaminergic polymorphic ventricular tachycardia (CPVT). Statins can affect skeletal muscle and produce statin-associated muscle symptoms (SAMS) but have no adverse effects on cardiac muscle. These contrasting effects may be due to differences in how statins affect the skeletal (RyR1) and cardiac (RyR2) RyR. We searched PubMed to identify English language articles reporting the pathophysiology of the RyR, the effect of statins on RyR function, and on RyR-associated genetic diseases. We selected 150 articles for abstract review, 96 of which provided sufficient information to be included and were reviewed in detail. Fifteen articles highlighted the interaction of statins with the RyR. Nine identified the interaction of statins with RyR1, six addressed the interaction of statins with RyR2, 13 suggested that statins reduce ventricular arrhythmias (VA), and seven suggested that statins increase the risk of malignant hyperthermia (MH). In general, statins increase RyR1 and decrease RyR2 activity. We identified no articles examining the effect of statins on CPVT, a condition often caused by defects in RyR2. Statins appear to increase the risk of MH and decrease the risk of ventricular arrhythmia. The effect of statins on CPVT has not been directly examined, but statins' reduction in RyR2 function and their apparent reduction in VA suggest that they may be beneficial in this condition.

Sacubitril/valsartan therapy and supraventricular arrhythmias detected through remote monitoring in heart failure patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Sacubitril/valsartan (S/V) has demonstrated a significant benefit in decreasing mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF) when compared to angiotensin inhibition. Recent studies demonstrated that the benefits of S/V encompass a positive cardiac remodeling, leading to a reduction of ventricular arrhythmias. The effect of S/V on the supraventricular arrhythmic burden is still unknown. Purpose To evaluate the effect of sacubitril/valsartan on the supraventricular arrhythmic burden in HFrEF patients with an implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy-defibrillator (CRT-D) and remote monitoring. Methods The SAVE THE RHYTHM is a multicentre, observational, prospective registry is enrolling all patients with HFrEF, ICD or CRT-D actively followed through remote monitoring and starting treatment with sacubitril/valsartan. All patients are followed-up at least one year after sacubitril/valsartan start. The primary endpoint is the number of sustained atrial tachycardia or AF (AT/AF). Secondary endpoints include incidence of AT/AF in the total population, total burden of AT/AF (defined as the percentage of time in AT/AF per day), mean number of premature ventricular contractions (PVC) per hour and percentage of biventricular pacing per day (in patients with CRT-D). All primary and secondary endpoints are collected through remote monitoring. Results At the time of the second ad interim analysis, 188 patients (85.2% male, age 68 ± 10 years) were consecutively enrolled. In patients without permanent AF, treatment with S/V was associated with a reduced incidence of AT/AF episodes, which changed from 32.6% (before treatment start) to 24.3%, 20.5% and 6.9% according to the sacubitril/valsartan dose (24/26 mg, 49/51 mg and 97/103 mg respectively; p= 0.041). A significant decrease in the median annual number of AT/AF episodes was also seen in these patients (16/year before treatment; 12/year at 24/26 mg; 6/year at 49/51 mg and 1/year at 97/103 mg; p = 0.046). No significant differences were reported in terms of PVC or biventricular pacing (all p = NS). Patients with permanent AF experienced no benefits from sacubitril/valsartan therapy in terms of arrhythmic burden reduction. No new diagnosis of clinical AF was made after starting treatment with sacubitrl/valsartan in all patients. Conclusions Preliminary data suggest that therapy with S/V could reduce the episodes of AT/AF in patients with HFrEF and remote monitoring, and the benefit seems related to the maximum tolerated dose of S/V. No positive effect has been noted in patients with permanent AF.

Malignant arrythmic storm, stellate ganglion and diabetes mellitus

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Malignant arrhythmic storm (MAS) increases mortality more than three-fold according to current data. In the acute setting, besides resolving reversible causes, antiarrhythmics are the mainstay of treatment. The role of suppressing the local sympathetic nervous system activity, using stellate ganglion block (SGB) for example, is still being investigated. Purpose To show short-term efficacy of SGB in suppressing the ventricular arrhythmia recurrence in MAS. To identify subgroups of patients with better clinical response after SGB. Methods All consecutive patients with MAS, with standard treatment failure and ventricular arrhythmia recurrence, treated with ultrasound guided SGB, instilating 7ml of 0,5% Bupivacain. 58 MAS treated with SGB durin 2017 – 2020. There were 49 men (84,5%), average age 68,7 +/- 11,4, with average left ventricular EF 28,9 +/- 8,43%. There were 17 diabetics (29,3%). Results When we compare the numbers of defibrillations for sustained ventricular tachycardia 48 hours before and 48 hours after SGB, being the primary therapeutic endpoint in MAS, we see a 96,7% reduction (p &amp;lt; 0,001). When we evaluate ventricular arrhythmias treated with both antitachycardia pacing and shocks, then we see 90% reduction (p &amp;lt; 0,001). The effect of SGB in ventricular arrhythmia suppression was statistically significant during the entire follow-up of 8 days. When we analyzed the cohort, looking for groups showing better response after SGB in terms of ventricular arrhythmia reduction, the only group showing statistical significance in this regard are patients with diabetes mellitus. Conclusions In our cohort, stellate ganglion block is exceptionally effective in the treatment algorithm of malignant arrhythmic storm. SGB shows significantly higher efficacy in the subgroup of patients with diabetes mellitus. Abstract Figure. VA before and after BSG

Mexiletine for ventricular arrhythmias in patients with chronic coronary syndrome: a cohort study

Background The pharmacological therapy of ventricular arrhythmias in patients with unsuccessful or not feasible catheter ablation and contraindication or inefficacy to amiodarone and beta-blockers, is controversial. The present study investigated the effectiveness and tolerability of mexiletine in patients with recurrent ventricular arrhythmias and ischaemic heart disease, when the conventional antiarrhythmic therapy failed. Methods We enrolled all consecutive patients with unsuccessful/not feasible catheter ablation and ineffective/contraindicated amiodarone or beta-blockers, which started the mexiletine treatment for refractory ventricular tachycardia (VT) or ventricular fibrillation (VF) between January 2010 and January 2020. The primary endpoint was the total number of VT/VF episodes after the beginning of mexiletine therapy. The 2 secondary endpoints were the overall number of therapies released by implantable cardioverter-defibrillators (ICDs) and the discontinuation of the pharmacological therapy. The events occurring during the mexiletine treatment period were compared with those observed in a matched duration interval before the initiation of therapy. Results Thirty-four consecutive patients (27 males, 79.4%; mean age 74.0 ± 9.5 years) with ischaemic heart disease were finally analysed. The median of mexiletine treatment was 26.5 months (interquartile range: 18.75–38.25 months). After the mexiletine start, VT/VF episodes and ICD interventions significantly decreased (respectively: 74 vs 33 episodes, p = 0.002; 116 vs 52 interventions, p = 0.02) in comparison with a matched period without mexiletine. Six patients (13.9%) discontinued the treatment because of severe side effects. Conclusions The treatment period following the mexiletine start was associated with a significant reduction of ventricular arrhythmias. The rate of side effects requiring dosage reduction or interruption was not neglectable.

Ventricular Arrhythmia Burden as a Marker of Success Following Catheter Ablation of Ventricular Arrhythmias in Patients with Structural Heart Disease.

Background and ObjectivesThere is little emphasis on the efficacy of catheter ablation for ventricular arrhythmia (VA) when using VA burden reduction as a marker for success. We examined the efficacy of catheter ablation using VA burden, rather than VA recurrence as a marker of success, following catheter ablation of structural heart disease (SHD) related VA.MethodsCatheter ablation of SHD related VA was performed at a single centre over 4-years. VA episodes and implantable cardioverter defibrillator (ICD) therapies were recorded over the 6-months before and after final ablation. Outcomes were reported in terms of burden reduction and compared to singular VA recurrence.ResultsOverall, 108 patients were included in the study. Mean age 64.2±13.9 years, 86% male, mean left ventricular ejection fraction (LVEF) 42±16%. Median VA episodes and ICD therapy were significantly reduced after ablation (VA before: 10 [interquartile range, IQR: 2–38] vs. VA after: 0 [IQR: 0–2], p<0.001; anti–tachycardia pacing [ATP] before: 16 (IQR: 1.5–57) vs. ATP after: 0 [IQR: 0–2], p<0.001; shocks before: 1 [IQR: 0–5] vs. shocks after: 0 [IQR: 0–0], p<0.001). Procedural success at 6-months was significantly higher when considering ≥75% reduction in VA burden, rather than a singular VA-free survival (83% vs. 67%, p=0.001).ConclusionsThe vast majority (>80%) of patients achieve reduction in VA burden (≥75% reduction) after catheter ablation for VA. This data suggests that catheter ablation is highly therapeutic when procedure success is defined as reduction in VA, rather than using a single VA recurrence as a metric for failure.

Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic.

AimsOur objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19.Methods and resultsIn this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54–0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58–0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56–0.85, P < 0.001).ConclusionsDuring COVID-19, there was a 32% reduction in ventricular arrhythmias needing device therapies, coinciding with measures of social isolation. There was a 39% reduction in the proportion of patients with ventricular arrhythmias in states with higher COVID-19 incidence. These findings highlight the potential role of real-life stressors in ventricular arrhythmia burden in individuals with ICDs.Trial registrationAustralian New Zealand Clinical Trial Registry; URL: https://www.anzctr.org.au/; Unique Identifier: ACTRN12620000641998

Cardiac Resynchronization Therapy in continuous flow Left Ventricular Assist Device Recipients: A Systematic Review and Meta-analysis from ELECTRAM Investigators.

Whether cardiac resynchronization therapy (CRT) continues to augment left ventricular remodeling in patients with the continuous-flow left ventricular assist device (cf-LVAD) remains unclear. We performed a systematic review and meta-analysis of all clinical studies examining the role of continued CRT in end-stage heart failure patients with cf-LVAD reporting all-cause mortality, ventricular arrhythmias, and ICD shocks. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data. Eight studies (7 retrospective and 1 randomized) with a total of 1,208 unique patients met inclusion criteria. There was no difference in all-cause mortality (RR 1.08, 95% CI 0.86 - 1.35, p = 0.51, I2=0%), all-cause hospitalization (RR 1.01, 95% CI 0.76-1.34, p = 0.95, I2=11%), ventricular arrhythmias (RR 1.08, 95% CI 0.83 - 1.39, p = 0.58, I2 =50%) and ICD shocks (RR 0.87, 95% CI 0.57 - 1.33, p = 0.52, I2 =65%) comparing CRT versus non-CRT. Subgroup analysis demonstrated significant reduction in ventricular arrhythmias (RR 0.76, 95% CI 0.64 - 0.90, p = 0.001) and ICD shocks (RR 0.65, 95% CI 0.44 - 0.97, p = 0.04) in "CRT on" group versus "CRT off" group. CRT was not associated with a reduction in all-cause mortality or increased risk of ventricular arrhythmias and ICD shocks compared to non-CRT in cf-LVAD patients. It remains to be determined which subgroup of cf-LVAD patients benefit from CRT. The findings of our study are intriguing, and therefore, larger studies in a randomized prospective manner should be undertaken to address this specifically.