Antiarrhythmic Therapy Research Articles

Abstract 4141439: Catheter ablation and clinical outcomes among older Medicare beneficiaries with atrial fibrillation

Background: Catheter ablation (CA) is increasingly used for treatment of atrial fibrillation (AF). However, CA has not been widely adopted in the older population with AF. The aim of this study is to examine the risks of adverse outcomes following CA in older people with AF. Methods: Using 2014-2019 Medicare claims, we conducted a propensity score analysis of patients treated with CA within 6 months of new AF diagnosis to patients treated with only antiarrhythmic therapy in the 6-month period. The outcome follow-up began after the 6-month period. Cox proportional hazards models were used to estimate hazard ratios (HR) for the composite and individual endpoints from CABANA trial (death, stroke, major bleeding or cardiac arrest) and CASTLE-AF trial (death or heart failure). Subgroup analyses were performed by sex, race-ethnicity, social deprivation index, frailty and dementia. Results: The study population comprised of 14623 AF patients (mean age, 76.1±7.6 years; 55% female, 28% frailty, 13% dementia), including 8% receiving CA. The mean follow-up was 1.8 years. Compared to patients with only antiarrhythmic therapy, patients treated with CA had lower rates of CABANA endpoints (CA vs antiarrhythmic therapy: 5.6 vs 11.7 per 100 person-years; HR:0.72, 95%CI:0.66-0.77) and CASTLE-AF endpoints (6.5 vs 13.8 per 100 person-years; HR:0.72, 95%CI:0.67-0.78). The benefits of CA were consistent in both female and male for CABANA endpoints (female: HR:0.71, 95%CI:0.64-0.79 and male: HR:0.72, 95%CI:0.65-0.81) and CASTLE-AF endpoints (female: HR:0.65, 95%CI:0.59-0.73 and male: HR:0.78, 95%CI:0.71-0.87), and in both frail and non-frail patients for CABANA endpoints (frail: HR:0.72, 95%CI:0.66-0.80 and non-frail: HR:0.70, 95%CI:0.63-0.77) and CASTLE-AF endpoints (frail: HR:0.89, 95%CI:0.81-0.97 and non-frail: HR:0.69, 95%CI:0.63-0.75). Similar trends were observed for subgroups defined by race-ethnicity, social deprivation index, and dementia. Conclusions: These findings suggest that CA may be beneficial for older AF patients. Nonetheless, further investigation of the safety and efficacy of CA given to older patients in well-designed interventional trials are warranted.

Abstract 4134792: SIRTUIN5 Modulates Na + /Ca 2+ Handling Via Oxidative Stress Dependent Manner In Mouse Heart

Background: The cardiac Na + channel Na V 1.5 (encoded by SCN5A ) governs cardiac inward Na + current (I Na ) and the fast upstroke and plateau phases of the cardiac action potential. Mutations in Na V 1.5 can cause acquired or inherited arrhythmias and conduction diseases, including ~20% of cases of Brugada Syndrome (BrS). Changes in I Na can impact Ca 2+ handling and cardiac excitation-contraction coupling. We have previously shown that SIRT1-mediated deacetylation of Na V 1.5 increased I Na . Recently, potential mutations (including P114T) in SIRT5, another NAD + -dependent deACYLase in the Sirtuin family localized to mitochondria, were identified in small families with BrS. Hypothesis: Sirt5 dysfunction evokes arrhythmias via Na + and Ca 2+ mishandling in an oxidative stress-dependent manner in mouse hearts. Aims: To explore the potential role of SIRT5 in BrS using heterologous expression systems and homozygous P114T-Sirt5 knock-in (P114T-KI) mice. Methods: Protein expression and physical interactions were detected by immunoprecipitation and immunoblot. The effects of SIRT5 on Na + current was measured using patch clamp in HEK cells and mouse cardiac myocytes. Confocal microscopy was used to measure reactive oxygen species (ROS) and for Ca 2+ imaging. Results: Both WT and P114T-SIRT5 co-immunoprecipitate with Na V 1.5, but WT increased peak I Na in HEK cells while P114T did not (Fig A,B). Live-cell staining using DCFDA or mitoSOX showed that P114T-KI hearts had increased basal ROS and were more sensitive to oxidative stress induced by H 2 O 2 than WT littermates. P114T-KI hearts had increased Na + /Ca 2+ exchange protein 1 (NCX1) expression, and Langendorff-perfused hearts displayed abnormal Ca 2+ handling and arrhythmias (Fig C). Notably, treatment with the mitochondrial ROS scavenger mitotempo mitigated the aberrant Ca 2+ handling and arrhythmias. Conclusion: These findings suggest that the P114T-SIRT5 causes abnormal Na + and Ca 2+ handling and arrhythmias in a ROS-dependent manner, highlighting potential mechanisms underlying BrS. This finding may pave the way for the use of SIRT5 or its activators as novel anti-arrhythmic therapies in the future.

On the choice of antiarrhythmic drug in patients with ventricular arrhythmia of mixed character

Background. The choice of an antiarrhythmic drug, proof of its effectiveness and safety in a short period of time in patients with non-coronary ventricular arrhythmia are the most pressing problems of practical arrhythmology. Objective. To resolve the issue of choosing an antiarrhythmic drug in patients with a mixed nature of ventricular arrhythmia, several ectopic foci, and to optimize further tactics for their management. Design and methods. Of 167 patients with ventricular arrhythmia distribution during periods of wakefulness who performed a stress test, 32 individuals with non-coronary arrhythmias of a mixed nature (by the participation of the autonomic nervous system) were selected. All patients underwent an acute pharmacological stress test with a beta-blocker. Antiarrhythmic therapy was selected under the control of multi-day ECG telemonitoring. Results. In the pretest of exercise tests, single ventricular parasystole was recorded in all 32 patients. In 3 patients, the arrhythmia persisted throughout the entire load, in 4 patients it progressed, in 25 patients the parasystole of the initial morphology disappeared, and at the peak of the load/early recovery period, arrhythmia of a different morphology appeared. Indications for drug treatment were determined for all patients with the choice of the drug after acute pharmacological tests. Then, therapy with two antiarrhythmic drugs was initiated using multi-day ECG telemonitoring, the purpose of which was to control the efficacy, safety, choice of doses and time of drug administration. On days 5–6, combination therapy was effective in 25 patients (78 %). Conclusion. With the help of stress tests, it is possible to accelerate not only the search for the cause of ventricular arrhythmia, but also the choice of a personalized method of treatment. Supplementing the examination with pharmacological tests allows predicting the result of combined antiarrhythmic therapy with a beta-blocker and a class IС drug with an anticholinergic effect.

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study.

This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding. Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

Yield of Coronary Assessment in Sustained Monomorphic Ventricular Tachycardia

Coronary assessment is frequently conducted in patients with sustained monomorphic ventricular tachycardia (SMVT); however, its yield and subsequent treatment implications remain unclear. This study aimed to determine the prevalence of coronary artery disease (CAD) in patients presenting with SMVT, factors influencing clinician referral for coronary assessment, and clinical outcomes based on revascularisation or medical management of CAD. Consecutive patients presenting with acute SMVT requiring inpatient admission between 2017 and 2022 were identified. A total of 249 individual patients with SMVT were identified, with 140 undergoing coronary assessment. Referral for coronary assessment was driven by chest pain (p<0.001) and increased troponin kinetics (p<0.001). No patient with SMVT had an acute coronary occlusion. Significant CAD was found in 48 (34%) patients, and traditional ischaemic features did not predict significant CAD. Nineteen (40%) patients with significant CAD underwent revascularisation (n=15 percutaneous coronary intervention, n=4 coronary artery bypass grafting). There was no significant difference in time to ventricular tachycardia (VT) recurrence between revascularised and medically managed CAD (hazard ratio 1.670; 95% confidence interval 0.756-3.687; p=0.199). A total of five of six patients who underwent a revascularisation-only strategy (no upfront antiarrhythmic therapy or ablation) had VT recurrence (median time to recurrence 8.9 months). Despite being frequently performed, coronary assessment in SMVT has only modest yield, with no patients having an acute coronary occlusion. Traditional clinical factors of ischaemia did not improve this yield. Revascularisation alone did not improve freedom from VT.

Drug therapy and catheter ablation for management of arrhythmias in continuous flow left ventricular assist device's patients. A Clinical Consensus Statement of the European Heart Rhythm Association and the Heart Failure Association of the ESC.

Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure. Although these devices effectively improve survival, atrial and ventricular arrhythmias are common with a prevalence of 20-50% at one year after LVAD implantation. Arrhythmias predispose these patients to additional risk and are associated with considerable morbidity from recurrent implantable cardioverter-defibrillator (ICD) shocks, progressive failure of the unsupported right ventricle, and herald an increased risk of mortality. Management of patients with arrhythmias and LVAD differs in many aspects from the general population heart failure patients. These include ruling out the reversible causes of arrhythmias that in LVAD patients may include mechanical irritation from the inflow cannula and suction events. For patients with symptomatic arrhythmias refractory to medical treatment, catheter ablation might be relevant. There are specific technical and procedural challenges perceived to be unique to LVAD-related ventricular tachycardia ablation such as vascular and LV access, signal filtering, catheter manoeuvrability within decompressed chambers, and electroanatomic mapping system interference. In some patients, the arrhythmogenic substrate might not be readily accessible by catheter ablation after LVAD implantation. In this regard, the peri-implantation period offers a unique opportunity to surgically address arrhythmogenic substrate and suppress future ventricular tachycardia recurrences. This document aims to address specific aspects of the management of arrhythmias in LVAD patients focusing on anti-arrhythmic drug therapy and ablations.

Incidence of systolic heart failure and need for implantable cardiac defibrillators in patients with atrial fibrillation who had catheter ablation versus antiarrhythmic medical therapy

Abstract Background The CASTLE-AF trial demonstrated that patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) who underwent catheter ablation (CA) showed improved patient outcomes. These outcomes included a reduction in all-cause mortality and heart failure hospitalizations along with an improvement in left ventricular ejection fraction, when compared to those receiving medical therapy alone. However, there is no data regarding development of novel HFrEF and the need for implantable cardiac defibrillator (ICD) in patients with AF who underwent CA vs. those on antiarrhythmic therapy (AAD). Purpose This study aims to assess if there is a difference in the development of HFrEF and the need for ICD intervention amongst AF patients who underwent CA vs. those on AAD. We hypothesize that patients with AF who underwent CA will have a decrease in the development of HFrEF and mitigation in the need for ICD intervention compared to AAD alone. Methods A large retrospective, multicentre database was utilized to identify patients aged 18-80 with AF from 2017-2023. Two cohorts were subsequently established based on treatment received: 1) CA vs. 2) AAD (amiodarone, flecainide, dronedarone, dofetilide, propafenone, sotalol). Patients with crossover between the groups were excluded. Student’s t-test was performed to compare baseline characteristics between cohorts. Relevant comorbidities, atrial fibrillation types, and cardiovascular medications were used for propensity matching. Kaplan Meier curves were calculated to compare outcomes at 5 years such as HFrEF development, ICD implantation, mortality, and hospitalizations. Results Patients that underwent CA (n=32,774) and AAD (n=345,882) were propensity matched yielding 32,670 patients per cohort. CA demonstrated a significantly decreased need for ICD intervention compared to AAD (1.69% vs. 3.28%; HR=0.559; 95% CI [0.503, 0.621], log rank p&amp;lt;0.0001). Secondary outcomes showed significant reduction in development of systolic heart failure (4.83% vs. 10.60%; HR=0.499; 95% CI [0.467, 0.533], log rank p&amp;lt;0.0001), overall hospitalizations (12.03% vs. 27.32%; HR=0.440; 95% CI [0.420, 0.461], log rank p&amp;lt;0.0001), and all-cause mortality (2.38% vs. 14.19%; HR=0.188; 95% CI [0.174, 0.203], log rank p&amp;lt;0.0001) with catheter ablation. Conclusions Patients that underwent CA had a significant reduction in development of systolic heart failure and mitigation in the need for ICD implantation when compared to those on AAD alone. Randomized clinical trials are needed to better understand this relationship and to further define which subpopulation of atrial fibrillation patients would derive the most benefit from CA.

Strategic timing- early and delayed catheter ablation in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia. AF catheter ablation (CA) is superior to antiarrhythmic drug (AAD) therapy in maintaining sinus rhythm. However, not much is known regarding the optimal timing of the ablation. Purpose This review aims to examine the evidence supporting both early and delayed ablation approaches, as well as explore their respective disadvantages. Methods We performed an electronic search in databases such as PubMed, ScienceDirect, Springer, Wiley Online Library, focusing on studies published from 2013 until 2022 and including both observational studies and randomized controlled trials (RCTs). Left atrial diameter and ejection fraction (EF) were assessed. The limit between early and delayed ablation was set to be 3 years, considering delayed CA studies with a diagnosis-to-ablation-time (DAT) of 3 years or more, and early CA studies with a DAT of less than 3 years. Included studies were selected according to our eligibility criteria: observational studies or RCTs that included patients with symptomatic paroxysmal or persistent AF that underwent ablation using either radiofrequency or cryoballoon approach or both approaches, studies that reported DAT, studies that included a follow-up period, studies that evaluated AF recurrence or AF burden. Studies that included a surgical ablation, a hybrid ablation approach, or ablation for arrhythmias other than AF were excluded. Results Ten studies were selected out of 1387 identified records. After a follow-up period of 1 year, the early ablation subgroup had a lower mean AF recurrence rate (31.1%) compared to that of the delayed ablation subgroup (37.7%) ( p&amp;lt;0.0004). The median AF recurrence rate in radiofrequency ablation group was (47.8%) in comparison to the AF recurrence rate in cryoablation group which was (27.4%) (p&amp;lt;0.0001). In studies that included paroxysmal AF patients exclusively, the AF recurrence rate was directly proportional to the DAT(R=0.95). Conclusion Our results demonstrate that DAT correlates with recurrence rate at 1 year following AF CA, the shorter the DAT the better the outcome especially in paroxysmal AF population.Prisma study selection flow diagramCorrelation between DAT-AF recurrence

Atrial fibrillation recurrence rates in patients with transthyretin cardiac amyloidosis undergoing pulmonary vein isolation: a comparative retrospective study with propensity score matching

Abstract Background Atrial fibrillation (AF) affects up to 70% of individuals diagnosed with transthyretin cardiac amyloidosis (ATTR CA) [1]. AF ablation is frequently considered in the management of these patients, but there is a lack of data about outcomes of the procedure in this population. Purpose This study aims to evaluate AF recurrence rates and long-term AF recurrence-free survival in patients with ATTR CA undergoing pulmonary vein isolation (PVI). Methods A single-center retrospective study was conducted, including all patients diagnosed with ATTR CA who underwent PVI from 2016 to 2023. We compared patients with amyloidosis (cases) to those without (controls), employing propensity score matching for age, gender, AF type (paroxysmal vs. persistent), BMI, diabetes, arterial hypertension diagnosis, antiarrhythmic drug therapy post-index ablation, and left atrium (LA) volume assessed by 3D rotational angiography (3DRA). Results 16 patients with CA were matched to 16 patients without (32 patients in total). After matching, the populations demonstrated comparable baseline characteristics (figure 1). The study consistently revealed a higher AF recurrence rate, after PVI, in the CA group (81.3%) compared to the control group (37.5%) at the last follow-up (p-value 0.01) (median follow-up 1255 ± 1055 days in CA and 1491 ± 464 days in control group), as well as a significantly lower long-term AF-recurrence free survival (log-rank p = 0.01 – figure 2). Additionally, the recurrence rate at 1-year post-procedure was 56.25% in the CA group and 18.75% in the control group (p-value 0.03). Conclusions Pulmonary vein isolation remains a viable treatment option for individuals with ATTR CA. However, it proved less effective (or less durable) than in the general population without the disease, both at 1-year follow-up and for longer periods, as shown also with recurrence-free survival rate. Further studies are warranted to determine the optimal treatment strategy for this specific population.Baseline Characteristics fig. 1Kaplan Meyer fig. 2

Role of ventricular tachycardia cycle length in the outcomes after catheter ablation or antiarrhythmic drugs in the SURVIVE-VT trial

Abstract Background It has been suggested that antiarrhythmic drugs (AAD) are less effective and safe in slow ventricular tachycardia (VT) due to their effect on conduction velocity, which could stabilize reentry. Conversely, catheter ablation aims to disrupt the VT circuit. Because of the distinct mechanisms of action of AAD and catheter ablation on the VT circuit, VT cycle length (VT-CL) may play a crucial role in determining their therapeutic efficacy. Therefore, VT-CL could be important in selecting VT treatment. Purpose The aim of this study was to assess the impact of VT-CL on outcomes following catheter ablation or antiarrhythmic drugs in AAD-naïve patients with ischemic cardiomyopathy presenting with VT. Methods This is a post hoc analysis of the previously published Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia (SURVIVE-VT) trial. In summary, 144 patients with ischemic cardiomyopathy and symptomatic VT were randomized to receive either catheter ablation (N=71) or AAD (N=73) as first-line therapy. We analyzed VT recurrence, implantable cardioverter-defibrillator (ICD) therapies, and the incidence of slow/incessant VT/VT storm using Cox proportional hazard models, with treatment and VT-CL interaction terms, adjusted for age. Missing VT-CL data for five patients were imputed using the median value. Results In patients with chronic ischemic heart disease and VT treated with either AAD or catheter ablation, a significant interaction was observed between clinical VT-CL and treatment effect on VT recurrence (p=0.016 for the interaction). Specifically, slower VT cycle lengths were associated with higher rates of VT recurrence (hazard ratio per 10 ms [HR] 1.094, 95% confidence interval [CI] 1.015, 1.179; p=0.037) in patients treated with AAD, while no significant effect was observed in those undergoing catheter ablation (see Figure 1). Survival freedom from VT recurrence in patients with VT-CL ≥300ms was significantly higher in patients treated with catheter ablation (78.8% vs 58.1%, log-rank p=0.044, see Figure 2). As expected, VT-CL was significantly associated with a higher risk of slow/incessant VT/VT storm (HR per 10 ms 1.115, 95% CI 1.017-1.222, p=0.047) but was not associated with ICD therapies (HR per 10 ms 1.082, 95% CI 0.994-1.178, p=0.102). Conclusion VT-CL significantly influences treatment outcomes, with slower VT cycles associated with an increased risk of VT recurrence in patients treated with AAD, but not in those undergoing catheter ablation. Therefore, VT-CL should be taken into consideration when selecting the optimal therapy for patients with ischemic cardiomyopathy and VT.Figure 1Figure 2

Left atrial and left ventricular positive and negative remodeling after catheter ablation of atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is associated with negative remodeling of left atrium (LA) and in later stages of diseases with negative remodeling of left ventricle (LV). Can radiofrequency ablation (RFA) of pulmonary veins cure AF and retain progression of arrhythmia? Purpose This study evaluated positive and negative remodeling of LA and LV after RFA of pulmonary veins and a 7-year follow-up. The patients were divided into 4 groups on the basis of Pulmonary Vein Isolation Outcome Degree (PVIOD 1-4), a new measure for the efficacy of catheter ablation of AF. Methods One hundred seventeen patients with symptomatic drug-refractory paroxysmal and persistent AF were treated with RFA. At baseline and after a 7 years of follow-up, 2-dimensional echocardiography was performed to assess LA diameter, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF). Results After a 7-year follow-up 32.5% patients with successful single RFA of AF (PVIOD 1) showed significant positive LA and LV remodeling: LA diameter 39.3±0.6 vs 36.5±0.6 mm, p=0.0007; LVEDD 53.1±0.6 vs 50.9±0.7 mm, p=0.008; LVESD 34.7±0.8 vs 32.0±0.1 mm, p=0.005 and LVEF 56.8±0.8 vs 62.1±1.1 %, p=0.000008. In 29.1% of patients with success after multiple procedures (PVIOD 2) occurred significant reverse LA remodeling: LA diameter 41.9±0.7 vs 40.2±0.6 mm, p=0.04. Clinical success (PVIOD 3) after RFA was defined as a significant reduction in the number and duration of AF episodes with or without previously ineffective antiarrhythmic drugs (AAD) class I and III. In 14.5% of subjects with long-term clinical success (PVIOD 3 and baseline LA diameter 43.2±1.0 mm) remodeling of LA and LV was not occurred. In 23.9% of patients with procedural and clinical failure after RFA (PVIOD 4) long-term follow-up showed significant negative remodeling of LA and LV: LA diameter 44.7±0.7 vs 47.4±0.7 mm, p=0.006; LVEDD 52.8±0.9 vs 57.1±0.6 mm, p=0.0006; LVESD 36.5±1.1 vs 40.7±1.2 mm, p=0.006 and LVEF 50.7±1.7 vs 43.8±1.8 %, p=0.004. Conclusions Single successful RFA of pulmonary veins in early stage of AF with normal LA diameter cure arrhythmia, which was proved with LA and LV positive remodeling after a 7-year follow-up. With increase of LA diameter, the success of RFA decrease. The multiple procedures slow the progression of AF, but are less effective because of long periods of time between them. Clinical success and role of AAD therapy are also important in AF management. If AF is not treated with RFA properly on time it becomes progressive disease.

Clinical characteristic and zero-fluoroscopy ablation outcomes of tachyarrhythmias in pregnant: a single center study

Abstract Background Although recommended avoid any intervention during gestation in cases of drug refractory of arrhythmias catheter ablation may be necessary in pregnant women. Purpose To present clinical characteristics and outcomes of zero-fluoroscopy catheter ablation during gestation. Methods This prospective, single center study included 84 cases of tachyarrhythmias during gestation. In 44 cases of drug refractory was performed catheter ablation without fluoroscopy (main group). We evaluated the further course of gestation and obstetric outcomes after ablation in comparison with pregnant with antiarrhythmic therapy of tachyarrhythmias (n=40, control group). Results Both groups were comparable by mean age of pregnant (28.2±4.2 vs. 27.3±3.9 years, p=0.093) and mean duration of gestation (24 ±3.4 vs. 23.8 ±3.2 weeks, p=0.123). New onset arrhythmia prevailed in both groups (64% vs. 55%, p=0,280). Supraventricular tachycardia was the most common arrhythmia during gestation (81,8% vs. 52,5%, p=0,005), which was followed by premature contraction (13,6% vs. 40%, p=0,007). Cases of ventricular tachycardia were rare (4,6% vs. 7,5%, p=0,665). Ablation was performed under the guidance of CARTO (45%) and Ensite Precision systems (55%) without using fluoroscopy in all cases. Acute procedural success of zero-fluoroscopy ablation was in 100% with mean procedural time 71±17 minutes without any complication. Outcomes: further course of gestation characterized by increased incidence of uterine contractile activity and placental abruption only in main group (4,54%, p=0.464 and 2.3%, p=642 respectively). There were no differences in the rate of other complication: uterine blood flow violation (15.9% vs 12.9%, p=0.234) and preeclampsia (4.55% vs 5%, p=0.237). Vaginal type of delivery was in the majority of cases in both groups (82% vs 83%, p=0.242). Neonatal outcomes characterized with normal range of fetal birth weight (median 3207,39±485,61 vs. 3312,3±234,1 grams, p=0.709) and 5 minute Apgar score (median 8,4±1,6 vs. 8,7±1,2, p=0.921). There was no incidence of maternal and fetal mortality. In 12 month, follow-up all there was no arrhythmia recurrence. Conclusions Zero-fluoroscopy ablation of tachyarrhythmias in pregnant is feasible and can be safety performed during gestation in cases of drug refractory with benign outcomes.

Promising tools for future drug discovery and development in antiarrhythmic therapy.

Arrhythmia refers to irregularities in the rate and rhythm of the heart, with symptoms spanning from mild palpitations to life-threatening arrhythmias and sudden cardiac death (SCD). The complex molecular nature of arrhythmias complicates the selection of appropriate treatment. Current therapies involve the use of antiarrhythmic drugs (class I-IV) with limited efficacy and dangerous side effects and implantable pacemakers and cardioverter-defibrillators with hardware-related complications and inappropriate shocks. The number of novel antiarrhythmic drug in the development pipeline has decreased substantially during the last decade and underscores uncertainties regarding future developments in this field. Consequently, arrhythmia treatment poses significant challenges, prompting the need for alternative approaches. Remarkably, innovative drug discovery and development technologies show promise in helping advance antiarrhythmic therapies. Here, we review unique characteristics and the transformative potential of emerging technologies that offer unprecedented opportunities for transitioning from traditional antiarrhythmics to next-generation therapies. We assess stem cell technology, emphasizing the utility of innovative cell profiling using multi-omics, high-throughput screening, and advanced computational modeling in developing treatments tailored precisely to individual genetic and physiological profiles. We offer insights into gene therapy, peptide and peptibody approaches for drug delivery. We finally discuss potential strengths and weaknesses of such techniques in reducing adverse effects and enhancing overall treatment outcomes, leading to more effective, specific, and safer therapies. Altogether, this comprehensive overview introduces innovative avenues for personalized rhythm therapy, with particular emphasis on drug discovery, aiming to advance the arrhythmia treatment landscape and the prevention of SCD. Significance Statement Arrhythmias and sudden cardiac death account for 15-20% of deaths worldwide. However, current antiarrhythmic therapies are ineffective and with dangerous side effects. Here, we review the field of arrhythmia treatment underscoring the slow progress in advancing the cardiac rhythm therapy pipeline and the uncertainties regarding evolution of this field. We provide information on how emerging technological and experimental tools can help accelerate progress and address the limitations of antiarrhythmic drug discovery.

Comparison of Oral Procainamide and Mexiletine Treatment of Recurrent and Refractory Ventricular Tachyarrhythmias

Background: Antiarrhythmic therapy for recurrent ventricular arrhythmias (VAs) in patients having undergone catheter ablation and in whom amiodarone and/or beta-blockers were ineffective or contraindicated is a controversial issue. Purpose: The present study sought to compare the efficacy and tolerability of oral procainamide and mexiletine in patients with recurrent ventricular arrhythmias when the standard therapy strategy failed. Methods: All patients with an implantable cardioverter defibrillator (ICD) treated with oral procainamide or mexiletine for recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) in two cardiology divisions between January 2010 and January 2020 were enrolled. Patients were divided into group A (oral procainamide) and group B (mexiletine) and the two groups were compared to each other. The primary endpoint was the efficacy of therapy; the secondary endpoint was the discontinuation of therapy. All events that occurred during procainamide or mexiletine treatment were compared with a matched duration period before the initiation of the therapy. Antiarrhythmic therapy was considered effective when a ≥80% reduction of the sustained ventricular arrhythmias burden recorded by the ICD was achieved. Results: A total of 68 consecutive patients (61 males, 89.7%; mean age 74 ± 10 years) were included in this retrospective analysis. After a median follow-up of 19 months, 38 (56%) patients had a significant reduction in the VA burden. After multivariable adjustment, therapy with procainamide was independently associated with an almost 3-fold higher efficacy on VA suppression compared to mexiletine (HR 2.54, 95% CI 1.06–6.14, p = 0.03). Only three patients (9%) treated with procainamide presented severe side effects (dyspnea or hypotension) requiring discontinuation of therapy compared with six patients (18%) treated with mexiletine who interrupted therapy because of severe side effects (p = 0.47). Conclusions: Compared to mexiletine, oral procainamide had a higher efficacy for the treatment of recurrent and refractory VAs, and showed a good profile of tolerability.

Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study.

Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF. The nationwide Finnish anticoagulation in atrial fibrillation (FinACAF) registry-based linkage study covers all patients with new-onset AF in Finland during 2007-2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AAD), cardioversion, or catheter ablation. The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups (adjusted subdistribution hazard ratio (aSHR) 1.223, 95%-CI 1.187-1.261). Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95%-CI 0.695-0.749), more often in patients ≥75 years (aSHR 1.166, 95%-CI 1.108-1.227), while no difference between the sexes existed in patients aged 65-74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95%-CI 0.826-0.998) and ≥75 years (aSHR 0.521, 95%-CI 0.354-0.766), whereas there was no difference in patients aged 65-74 years. Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Macrophages enhance sodium channel expression in cardiomyocytes.

Cardiac macrophages facilitate electrical conduction through the atrioventricular-node (AV) in mice. A possible role for cardiomyocyte-macrophage coupling on the effect of antiarrhythmic therapy has not been investigated yet. Holter monitoring was conducted in LysMCrexCsf1rLsL-DTR mice (MMDTR) under baseline conditions and after an elctrophysiological stress test by flecainide. In vivo effects were recapitulated in vitro by patch-clamp experiments. The underlying mechanism was characterized by expression and localization analysis of connexin43 (Cx43) and voltage-gated-sodium-channel-5 (Nav1.5). ECG monitoring in MMDTR mice did not show any significant conduction abnormalities but a significantly attenuated flecainide-induced extension of RR- and PP-intervals. Patch-clamp analysis revealed that the application of flecainide to neonatal rat ventricular cardiomyocytes (CMs) changed their resting-membrane-potential (RMP) to more negative potentials and decreased action-potential-duration (APD50). Coupling of macrophages to CMs significantly enhances the effects of flecainide, with a further reduction of the RMP and APD50, mediated by an upregulation of Cx43 and Nav1.5 surface expression. Macrophage depletion in mice does not correlate with cardiac electric conduction delay. Cardiac macrophages amplify the effects of flecainide on electrophysiological properties of cardiomyocytes in vivo and in vitro. Mechanistically, formation of macrophage-cardiomyocyte cell-cell-contacts via Cx43 facilitates the recruitment of Nav1.5 to the cell membrane increasing flecainide effects.

Catheter ablation vs antiarrhythmic therapy for atrial fibrillation in heart failure with preserved ejection fraction

BackgroundClinical outcomes of patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) treated with catheter ablation (CA) vs antiarrhythmic therapy (AAT) are not well known. ObjectiveThis study compared morbidity and mortality of patients with AF and HFpEF treated with CA vs AAT. MethodsAF and HFpEF patients from January 2017 to June 2023 were identified in TriNetX, a large global population-based database. Patients with prior diagnosis of heart failure with reduced ejection fraction (HFrEF) or crossover between AAT and CA were excluded. Baseline characteristics including age, sex, body mass index, type of AF, comorbidities, and cardiovascular medications were compared. The 2 groups were 1:1 propensity score matched for outcomes analysis. All-cause mortality, cerebrovascular accident/transient ischemic attack, and acute heart failure were compared with Kaplan-Meier curves. ResultsPatients treated with CA (n = 1959) and AAT (n = 7689) were 1:1 propensity score matched, yielding 3632 patients with no significant differences in baseline characteristics. Compared with AAT, CA was associated with decreased mortality (9.2% vs 20.5%; hazard ratio [HR], 0.431; 95% confidence interval [CI], 0.359–0.518; P < .001). In addition, CA was associated with reduced HFpEF (HR, 0.638; 95% CI, 0.550–0.741; P < .001) and acute HFrEF (HR, 0.645; 95% CI, 0.452–0.920; P = .015). There was no difference in composite of cerebrovascular accident/transient ischemic attack (HR, 0.935; 95% CI, 0.725–1.207; P = .607). ConclusionIn this retrospective study of patients with AF and HFpEF, CA was associated with lower mortality and risk of acute heart failure compared with AAT.

The Effect of Extracorporeal Membrane Oxygenation in the Management of Refractory Ventricular Tachycardia Developed after Fontan Procedure (Case Report)

Aim: to evaluate the effect of extracorporeal membrane oxygenation (ECMO) as a life support in the treatment of a patient with refractory ventricular tachycardia developed after Fontan procedure. Patient and treatment. A 4-year-old child developed refractory ventricular tachycardia (up to 250 bpm) and hemodynamic depression 18 hours after the Fontan procedure. After the failure of cardiopulmonary resuscitation and antiarrhythmic therapy, resternotomy with central venoarterial (VA) ECMO support was performed, followed by diagnostic angiocardiography. Contrast-enhanced cavopulmonary angiography revealed stenosis of the left pulmonary artery, which was treated with balloon angioplasty and stenting.Results. Ventricular tachycardia resolved and sinus rhythm was restored within 24 hours after left pulmonary artery stenting, supported by continuous ECMO and antiarrhythmic therapy. On day 3, transthoracic echocardiography showed good single ventricle contractility after a trial weaning from ECMO. As a result, the ECMO support was removed and the sternum sutured. The patient was discharged from the hospital on day 47 in stable condition.Conclusion. The prompt initiation of VA ECMO support in a 4-year old patient with refractory ventricular tachycardia post-Fontan procedure along with the complex management of post-procedural residual tachycardia using a combination of antiarrhythmic agents helped restoring sinus rhythm and could contribute to preventing neurological complications.

Importance of Zinc Homeostasis for Normal Cardiac Rhythm

&lt;p&gt;Current arrhythmia therapies such as ion channel blockers, catheter ablation, or implantable cardioverter defibrillators have limitations and side effects, and given the proarrhythmic risk associated with conventional, ion channel-targeted anti-arrhythmic drug therapies, a new approach to arrhythmias may be warranted. Measuring and adjusting the level of particular ions that impact heart rhythm can be a simple and low-complication strategy for preventing or treating specific arrhythmias. In addition, new medicines targeting these ions may effectively treat arrhythmias. Numerous studies have shown that intracellular and extracellular zinc concentrations impact the heart's electrical activity. Zinc has been observed to affect cardiac rhythm through a range of mechanisms. These mechanisms encompass the modulation of sodium, calcium, and potassium ion channels, as well as the influence on beta-adrenergic receptors and the enzyme adenylate cyclase. &lt;/p&gt;&lt;p&gt; Moreover, zinc can either counteract or induce oxidative stress, hinder calmodulin or the enzyme Ca (2+)/calmodulin-dependent protein kinase II (CaMKII), regulate cellular ATP levels, affect the processes of aging and autophagy, influence calcium ryanodine receptors, and control cellular inflammation. Additionally, zinc has been implicated in the modulation of circadian rhythm. Additionally, zinc has been implicated in the modulation of circadian rhythm. In all the above cases, the effect of zinc largely depends on the normal or increased cellular level of zinc, which shows the importance of maintaining the serum and intracellular levels of zinc within the normal range.&lt;/p&gt;

Direct-to-catheter ablation versus second line catheter ablation for persistent atrial fibrillation: Effect on arrhythmia recurrence, AF burden, early left atrium remodeling and quality of life.

Catheter ablation has obtained class 1 indication in ablation of young, healthy patients with symptomatic paroxysmal atrial fibrillation (AF). Anti-arrhythmic drugs (AADs) remain first-line therapy before ablating persistent AF (PersAF). We sought to evaluate the efficacy of a direct-to-catheter ablation approach against catheter ablation post AADs in PersAF. In this DECAAF II subanalysis, patients were stratified into two subgroups: 'Direct-to-catheter' group comprising patients who had not received AADs prior to ablation, and'second-line ablation' group, comprising patients who had been on any AAD therapy at any time before ablation. Patients were followed over 18months. The primary outcome was AF recurrence. Secondary outcomes included AF burden, quality of life (QoL) that assessed by the AFSS and SF-36 scores, and changes in the left atrial volume index (LAVI) assessed by LGE-MRI scans. The analysis included 815 patients, with 279 classified as'direct-to-catheter' group and 536 classified as'Second-line ablation' group. The primary outcome was similar between both groups (44.8% vs 44.4%, p > 0.05), as was AF burden (20% vs 16%, p > 0.05). Early remodeling, reflected by LAVI reduction, was similar between the groups (9.1 [1.6-18.0] in the second-line ablation group and 9.5 [2.5-19.7] in the direct-to-catheter group, p > 0.05). QoL pre/post ablation was also similar (p > 0.05). On multivariate analysis, history of AAD was not predictive of AF recurrence(p > 0.05). Prior AAD therapy demonstrated minimal impact on atrial remodeling and QoL improvement, in addition to limited benefit on AF recurrence and burden post-ablation in patients with PersAF. Additional studies are warranted to explore the efficacy of catheter ablation as a first-line therapy in PersAF.