Safety observation of antiarrhythmic drug use in a patient with sinus bradycardia following atrial fibrillation radiofrequency ablation combined with cardiac neural ablation: a case report.

This study assessed the safety of Antiarrhythmic Drug (AAD) administration in a patient experiencing sinus bradycardia following radiofrequency ablation for Atrial Fibrillation (AF), followed by cardiac ganglion ablation. Post-AF radiofrequency ablation, the employment of AADs is a prevalent clinical practice; however, these drugs may exacerbate bradycardia, leading to increased patient discomfort and treatment complexity. The decision to employ AADs in patients with sinus bradycardia post-AF ablation poses a significant clinical challenge. This investigation aimed to ascertain the safety of AADs in such patients. The study encompassed a single case, wherein a patient with pre- and post-procedure sinus bradycardia was treated with AADs following AF radiofrequency ablation and cardiac ganglion ablation, with a subsequent safety assessment. The findings indicate that AADs can be safely administered to patients with sinus bradycardia after these procedures, offering valuable insights for clinical decision-making. This case report underscores the intricacies of post-AF ablation management in patients with sinus bradycardia and advocates for personalized therapeutic strategies. The results enhance the clinical knowledge regarding the safety of AADs in this patient subset and may guide future treatment protocols. Nonetheless, the study's conclusions are drawn from a single case, and further research with larger cohorts is essential to substantiate these findings and elucidate the long-term safety and efficacy of this therapeutic approach.

Effectiveness of a Triple Antiarrhythmic Drug Strategy for Arrhythmia Recurrence after Persistent Atrial Fibrillation Ablation.

BACKGROUND AND OBJECTIVE: Treating recurrent atrial arrhythmias after persistent atrial fibrillation (PeAF) ablation is often challenging. This single-center, prospective study aimed to observe the effectiveness of different combinations of oral antiarrhythmic drugs (AADs) in reverting to sinus rhythm (SR) in patients with recurrent atrial arrhythmias after PeAF ablation. METHODS: Forty-five patients who experienced recurrent atrial arrhythmias after PeAF ablation were included. Based on their medication regimens, patients were divided into two groups, with the study group being a triple-drug group (digoxin combined with amiodarone/ propafenone and ß-blocker), and the control group being a non-triple-drug group. RESULTS: The rate of reversion to SR was significantly higher in the study group (n = 29) than in the control group (n = 16) at 3 weeks (34.48% vs. 0%, p < 0.01) and 1 month (44.84% vs. 6.25%, p = 0.02) after initiating AADs. No patients with asymptomatic bradycardia were observed in either group. CONCLUSIONS: For patients with recurrent atrial arrhythmias after PeAF ablation, a regimen of low-dose digoxin combined with amiodarone/propafenone and ß-blocker may effectively improve short-term reversion rates.

Dofetilide for the treatment of premature ventricular complexes and ventricular tachycardia in patients with structural heart disease.

BACKGROUND: Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). OBJECTIVE: The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs). METHODS: In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%). RESULTS: During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55). CONCLUSIONS: Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.

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.

AN INTERNATIONAL PHYSICIAN SURVEY OF CURRENT ABLATION PRACTICES IN ATRIAL FIBRILLATION: AN AIM-AF SUBSTUDY.

BACKGROUND: Practice guidelines recommend Ablation (ABL) in atrial fibrillation (AF) for rhythm control; guidance for antiarrhythmic drugs (AADs) post-ablation is limited. OBJECTIVE: To understand AAD and ABL practices in USA and Europe. METHODS: An online survey of experienced cardiologists (CDs, n=360) and interventional electrophysiologists (EPs, n=269) was conducted. AAD and ABL related survey questions and responses were analyzed. RESULTS: ABL was preferred more often as first-line AF therapy (Rx) by US CDs/EPs (p<.001). ABL was selected to avoid AAD Rx by 46% (50% CDs, 40% EPs), prevent AF progression by 41% (36% CDs, 47% EPs) and for superior efficacy by 28% (27% CDs, 30% EPs), ABL was employed by 9% in asymptomatic AF (9% CDs, 10% EPs), by 14% in subclinical AF (13% CDs, 14% EPs), by 17% for first AF event (15% CDs, 18% EPs). Primary ABL was preferred in heart failure by 38%. Co-morbidities, age and left atrial size were limitations for ABL by 48%, 40% and 38%, respectively. AADs were used after ABL for AF/ atrial tachycardia (AT) prophylaxis by 34% for 3-6 months and 29% for 1-2 months. AADs were given for a single AF recurrence by 34%, bridging to re-ablation by 32%, and long-term Rx by 34%. AF/AT post-ABL was most often managed with amiodarone (42-48%). CONCLUSION: ABL was frequently preferred over AADs in symptomatic AF but was notably also used for asymptomatic and subclinical AF. Post-ABL AAD Rx for AF prophylaxis or recurrence was frequent with empiric amiodarone being the most often selected AAD.

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.

AIMS: 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. METHODS AND RESULTS: The nationwide Finnish anticoagulation in AF 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 (AADs), 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% confidence interval (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. CONCLUSION: Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Catheter Ablation Versus Antiarrhythmic Therapy for Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Clinical outcomes among patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) treated with catheter ablation (CA) versus antiarrhythmic therapy (AAT) are not well-known. OBJECTIVES: This study compared morbidity and mortality among patients with AF and HFpEF treated with CA versus AAT. METHODS: AF and HFpEF patients from January 2017-June 2023 were identified in TriNetX, a large global population-based database. Patients with prior diagnosis of HFrEF or crossover between AAT and CA were excluded. Baseline characteristics including age, sex, BMI, type of AF, comorbidities, and cardiovascular medications were compared. The two groups were 1:1 propensity matched for outcomes analysis. All-cause mortality, cerebrovascular accident (CVA)/transient ischemic attack (TIA), and acute HF were compared with Kaplan-Meier curves. RESULTS: Patients treated with CA (n=1959) and AAT (n=7689) were 1:1 propensity matched yielding 3632 patients with no significant differences in baseline characteristics. Compared to AAT, CA was associated with decreased mortality (9.2% vs. 20.5%; hazard ratio [HR]: 0.431; 95% confidence interval [CI]: 0.359 to 0.518; p<0.001). Additionally, CA was associated with reduced HFpEF (HR: 0.638; 95% CI, 0.550 to 0.741; p<0.001) and acute HFrEF (HR: 0.645; 95% CI, 0.452 to 0.920; p=0.015). There was no difference in composite of CVA/TIA (HR: 0.935; 95% CI: 0.725 to 1.207; p=0.607). CONCLUSION: In this retrospective study of patients with AF and HFpEF, CA was associated with lower mortality and risk of acute heart failure when compared with AAT.

Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats.

BACKGROUND: An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. METHODS: Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10 mg/kg) and CE (100 mg/kg) were orally given. After 1 h, 50 mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10 days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. RESULTS: Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1ß and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). CONCLUSION: Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.

Do extra-pulmonary triggers or autonomic neural activity affect rhythm control by anti-arrhythmic drugs in patients with post-ablation atrial fibrillation recurrence?

Background: The role of anti-arrhythmic drugs (AADs) in recurrent atrial fibrillation (AF) after catheter ablation (CA) is not fully understood. The aim of this study was to explore the effects of AADs in patients who recurred after AFCA depending on extra-pulmonary vein triggers (ExPVTs) and post-ablation heart rate variability (HRV) parameters. Methods: We analyzed 2,036 patients who underwent de-novo AFCA and 486 patients with post-AFCA recurrence who underwent rhythm control with AADs. We investigated the effects of ExPVTs and 3rd month HRV parameters on the post-AFCA recurrence and subsequent AAD responsiveness. Results: A total of 486 out of 2,036 patients developed clinical recurrence of AF and subsequently underwent rhythm control with AADs. 486 out of 310 patients (63.8%) remained free of second recurrence at 1-year. Post-AFCA recurrence was significantly higher in patients with ExPVT [Log-rank p < 0.001, HR 1.45 (1.16-1.83), p = 0.001] or higher 3rd month root mean square of the differences between successive RR intervals (rMSSD) [Log-rank p < 0.001, HR 1.36 (1.11-1.65), p = 0.003] than their counterparts. Patients with ExPVTs during the de-novo procedure had significantly higher 3rd month rMSSD (15.0 [11.0-23.0] vs. 17.0 [11.0-28.0], p = 0.022). Patients with high 3rd month rMSSD had higher rate of ExPVTs during the repeat procedure (n = 160, 41.0% vs. 22.2%, p = 0.019). Among patients with recurrent AF after AFCA, post-AAD recurrence did not differ depending on the presence of ExPVT [Log-rank p = 0.455, HR 1.12 (0.78-1.69), p = 0.436] or 3rd month rMSSD [Log-rank p = 0.457, HR 1.16 (0.87-1.55), p = 0.300]. Post-AAD recurrence did not differ between class IC and III AADs (p for interaction = 0.311). Conclusions: ExPVT and post-procedural high rMSSD are independent risk factors for post-AFCA recurrence but not for AAD response in patients with recurrent AF. AADs may suppress ExPVTs and modulate cardiac autonomic activity after post-AFCA recurrence.

Design and Rationale of a Pragmatic Randomized Clinical Trial of Early Dronedarone versus Usual Care to Change and Improve Outcomes in Persons with First-Detected Atrial Fibrillation - The CHANGE AFIB Study.

BACKGROUND: While there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes. METHODS: In this open-label pragmatic clinical trial nested within the Get With The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months. CONCLUSION: CHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes. CLINICALTRIALS: GOV #: - NCT05130268.

SARS-CoV-2 ORF 3a-mediated currents are inhibited by antiarrhythmic drugs.

AIMS: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to cardiovascular complications, notably cardiac arrhythmias. The open reading frame (ORF) 3a of the coronavirus genome encodes for a transmembrane protein that can function as an ion channel. The aim of this study was to investigate the role of the SARS-CoV-2 ORF 3a protein in COVID-19-associated arrhythmias and its potential as a pharmacological target. METHODS AND RESULTS: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and cultured human fibroblasts were infected with SARS-CoV-2. Subsequent immunoblotting assays revealed the expression of ORF 3a protein in hiPSC-CM but not in fibroblasts. After intracytoplasmic injection of RNA encoding ORF 3a proteins into Xenopus laevis oocytes, macroscopic outward currents could be measured. While class I, II, and IV antiarrhythmic drugs showed minor effects on ORF 3a-mediated currents, a robust inhibition was detected after application of class III antiarrhythmics. The strongest effects were observed with dofetilide and amiodarone. Finally, molecular docking simulations and mutagenesis studies identified key amino acid residues involved in drug binding. CONCLUSION: Class III antiarrhythmic drugs are potential inhibitors of ORF 3a-mediated currents, offering new options for the treatment of COVID-19-related cardiac complications.

Exploring the interplay between extracellular pH and Dronedarone's pharmacological effects on cardiac function.

Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Nav1.5 at pHe 7.0. The recovery from INa inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak INa, the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block INaLate. Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Nav1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration.

Long-term health-related quality of life and rhythm outcomes of catheter ablation versus antiarrhythmic drugs in patients with atrial fibrillation.

BACKGROUND: Data on long-term effects of catheter ablation vs antiarrhythmic drugs (AADs) on health-related quality of life (HRQoL) and atrial fibrillation (AF) burden are limited. OBJECTIVE: The study aimed to assess long-term HRQoL and rhythm data in patients with symptomatic AF. METHODS: The 75 patients who underwent ablation and 74 receiving AADs in the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial were followed for 48 months. The General Health subscale of the 36-Item Short-Form Health Survey, time to first AF episode ≥1 hour, and AF burden, recorded by implantable cardiac monitors, were compared. RESULTS: One hundred forty-seven patients completed follow-up, with 7 crossovers in the ablation group and 34 crossovers in the AAD group. General Health improved by ablation from a median of 62 points at baseline to 79.2 points at follow-up (P < .001) and by AADfrom a median of 67 to 77 points (P < .001), without treatment differences (P = .77). Time to first AF episode ≥1 hour was longer (median 257 days in the ablation group vs 180 days in the AAD group; P = .025). The cumulative AF burden during follow-up was lower in the ablation group (median 0.3%; interquartile range [IQR] 0%-1.4%) than in the AAD group (1.6%; IQR 0.1%-11.0%); P = .01. The cumulative reduction in AF burden compared with baseline was greater in the ablation group (median -89.5%; IQR -98.4% to -51.3%) than in the AAD group (-52.7%; IQR -92.6% to 263.6%); P < .001. CONCLUSION: HRQoL improvement in long-term did not differ between ablation and AAD groups despite a larger reduction in AF burden after ablation. The results should be interpreted in the light of a high crossover rate in the AAD group.

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.

BACKGROUND: 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. METHODS: 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 18 months. 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. RESULTS: 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). CONCLUSION: 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.

Cardiac Arrhythmias and Their Management: An In-Depth Review of Current Practices and Emerging Therapies.

Cardiac arrhythmias encompass a range of conditions characterized by abnormal heart rhythms, affecting millions globally and significantly contributing to morbidity and mortality. This review provides a comprehensive analysis of the current practices and emerging therapies in managing cardiac arrhythmias, covering their definition, classification, epidemiology, and the critical importance of effective management. It explores the pathophysiology underlying various arrhythmias, including the mechanisms of arrhythmogenesis, such as re-entry, automaticity, and triggered activity. The review details the latest diagnostic tools, including ECG, Holter monitoring, and electrophysiological studies, and discusses the clinical presentation of different arrhythmias, from supraventricular to ventricular types and bradyarrhythmias. We examine current pharmacological and non-pharmacological treatment strategies, such as antiarrhythmic drugs, catheter ablation, and device therapy, highlighting their efficacy and limitations. Furthermore, the review delves into emerging therapies, including advanced catheter ablation techniques, novel antiarrhythmic agents, gene therapy, and innovative device technologies like leadless pacemakers and subcutaneous implantable cardioverter-defibrillators (ICDs). Special considerations for managing arrhythmias in diverse populations, including pediatrics, the elderly, and pregnant women, are discussed. Additionally, the review explores future directions in arrhythmia management, emphasizing personalized medicine, artificial intelligence applications, and the integration of advanced technologies in diagnosis and treatment. By synthesizing current knowledge and prospects, this review aims to enhance understanding and promote advancements in the field, ultimately improving patient outcomes with cardiac arrhythmias.

Efficacy of prescribing Inderal for polymorphic ventricular tachycardia in a young patient with the normal QT interval: A case report study.

Polymorphic ventricular tachycardia (PVT) is a group of life-threatening heart rhythm disorders. These arrhythmias share similar electrocardiographic characteristics but require different modes of therapy for effective treatment. It is important to note that the medications that are considered the first-line treatment for one type of PVT may not be appropriate for another type, and may worsen the condition. Therefore, it is crucial to accurately diagnose the type of PVT before initiating treatment to provide the most effective therapy for the patient. A 42-year-old man was admitted to the emergency department with dyspnea, Levine sign, and severe chest pain. His electrocardiogram showed ST elevation, and the QT interval was normal. The patient was sent to the cath lab based on the treatment protocols. According to the results of angiography, three coronary arteries were severely obstructed. His coronary arteries did not open during percutaneous coronary intervention; thus, the healthcare team decided on open heart surgery. He suffered from recurrent PVT following open heart surgery and did not respond to any of the drugs suitable for this type of tachycardia. Inderal prevented the recurrence of ventricular tachycardia (VT) in a patient with polymorphic VT without QT prolongation, contrary to the healthcare team's expectations. Inderal was used as the last line of treatment because this patient's arrhythmia was polymorphic VT without QT prolongation. Inderal is typically used for treating VT in patients with long QT syndromes and heart structural disorders. This case report aims to highlight the impact of Inderal on polymorphic tachycardia, specifically in cases where the QT interval is not elongated. In this particular case, the standard treatment approaches were ineffective in preventing reversibility, but Inderal proved to be successful. Therefore, we feel it is important to document and share this case.

Metabolic and Pharmacokinetic Profiling Studies of N, N-Dimethylaniline-Heliamine in Rats by UHPLC-Q-Orbitrap MS/MS.

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration-time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity.

The Role of Sodium Glucose Co-Transporter 2 Inhibitors in Atrial Fibrillation: A Comprehensive Review.

Atrial fibrillation (AF) is the most prevalent arrhythmia among adults worldwide, frequently co-occurring with comorbidities such as Heart Failure (HF) and Type 2 Diabetes Mellitus (T2DM). This association contributes to increased morbidity and mortality, elevated healthcare costs, and diminished quality of life. Consequently, preventing or delaying the onset and recurrence of AF is crucial for reducing the incidence of complications. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), due to their multifaceted pharmacological actions, have been proposed as potential therapeutic agents in the management of AF. However, current evidence from both animal models and clinical studies remains inconclusive. This narrative literature review aims to provide a comprehensive analysis of existing evidence on the impact of SGLT2is on the prevalence, incidence of new-onset, and recurrence of AF in diabetic populations and patients with HF. Numerous observational studies, predominantly retrospective, suggest a consistent reduction in AF risk with SGLT2is, while randomized controlled trials (RCTs) have yielded mixed results, with some demonstrating benefits and others not reaching statistical significance. The heterogeneity in study outcomes, population characteristics, follow-up duration, and specific SGLT2is used, as well as potential biases, underscore the need for further extensive and rigorous RCTs to establish definitive conclusions and elucidate the underlying mechanisms.

Ketamine Terminating Persistent Ventricular Tachycardia.

Ventricular tachycardia (VT) is an arrhythmia associated with sudden cardiac death. VT storm is a complication of persistent VT requiring immediate antiarrhythmic therapy. In refractory cases, adjunctive therapy includes sedation/mechanical ventilation or catheter ablation. This case highlights a patient with ischemic cardiomyopathy in refractory VT storm terminated by administration of ketamine.