Impact of Physical Activity in Patients With Atrial Fibrillation Undergoing Catheter Ablation: The Multicenter Randomized BE-ACTION Trial.

BACKGROUND: Arrhythmia recurrence after pulmonary vein isolation (PVI) is common. We conducted a multicenter, randomized trial to determine the impact of increased physical activity on atrial fibrillation recurrence after PVI. METHODS: From 2018 to 2020, we randomly assigned 200 patients with atrial fibrillation to the ACTION or NO-ACTION group in 4 different centers in the local country of Brandenburg, Germany. Patients were eligible if they were scheduled to undergo PVI, aged ≥50 to ≤77 years, body mass index ≥23 to ≤35 kg/m2, and accepted wearing an activity tracker allowing 24-hour activity monitoring via mobile app. Patients in the ACTION group were actively remote-controlled via transmitted activity data by a physiotherapist, and individual motivational interviewing call sessions were scheduled with each ACTION patient every 2 weeks. The primary end point was the composite of recurrence of any atrial arrhythmia >30 seconds, additional ablation procedure, cardioversion, and new onset of antiarrhythmic drugs earliest after 90 days after index PVI over 12 months. RESULTS: Overall, the median age of patients was 66 (interquartile range, 61-71) years, 33.5% were women, and 52% had persistent atrial fibrillation. The number of steps per day increased in both groups of patients from baseline to 12 months (P<0.001). The absolute increase in steps per day did not differ between patients in the ACTION group with +3205 steps (597-4944) compared with those in the NO-ACTION group +2423 steps (17-4284), P=0.325. Unadjusted intention-to-treat analysis showed no difference in the primary composite end point in the ACTION group (27.3%) versus the NO-ACTION group (32.7%), P=0.405. CONCLUSIONS: Physical activity improved in patients after PVI. The present randomized controlled trial shows that activity tracker and motivational calls to increase physical activity versus activity tracker alone did not reduce the occurrence of the primary composite end point of atrial fibrillation recurrence or the absolute increase in steps per day. REGISTRATION: URL: https://www.cochranelibrary.com; Unique identifier: DRKS00012914.

Estudo Randomizado Comparando a Ablação por Cateter com o PVAC Gold vs. Tratamento com Fármacos Antiarrítmicos em Pacientes Idosos com Fibrilação Atrial Sintomática / Randomized Study Comparing Radiofrequency Ablation with the PVAC Gold System vs. Antiarrhythmic Drugs in Elderly Patients with Symptomatic Atrial Fibrillation

Resumo Fundamento Não existem estudos randomizados comparando a manutenção do ritmo sinusal após ablação por cateter (AC) em relação ao tratamento com fármacos antiarrítmicos (AA) em pacientes idosos portadores fibrilação atrial (FA) paroxística. Objetivos Comparar os resultados clínicos do isolamento das veias pulmonares (VPs) com o cateter PVAC Gold de segunda geração com o uso de AA em idosos com FA paroxística sintomática, recorrente, apesar do uso de fármacos AA. Métodos Sessenta pacientes com FA paroxística ≥ 65 anos e sem cardiopatias estruturais foram randomizados para duas formas de tratamento: grupo 1: AC e grupo 2: AA. O desfecho primário foi a taxa livre de recorrência de FA após pelo menos um ano de seguimento. Os desfechos secundários foram: progressão para formas persistentes de FA, impacto na qualidade de vida (QVFA) e complicações. O nível de significância adotado na análise estatística foi de 5% (p<0,05). Resultados A taxa livre de recorrência de FA foi de 80% (10% com amiodarona) no grupo AC, após 1,3 procedimentos por paciente e de 65% no grupo AA (60% com amiodarona), (p = 0,119) num seguimento médio de 719 dias (Q1: 566; Q3: 730). A taxa livre de FA persistente foi de 83,4% no grupo AC e de 67,7% no grupo AA (p = 0,073). Ambas as estratégias apresentaram melhora no escore de QVFA durante o seguimento (p < 0,001), sem diferença entre os grupos. Embora sem repercussão clínica ou impacto no teste de avaliação intelectual, 25% dos pacientes do grupo PVAC apresentou sinais de embolização cerebral na RNM cerebral. Conclusões Ambas as estratégias para manutenção do ritmo sinusal promoveram melhora na qualidade de vida de pacientes idosos com FA sintomática, sem diferença estatística nos desfechos clínicos preconizados. Estudos adicionais usando tecnologias com melhor perfil de segurança são necessários para avaliar os benefícios da AC em pacientes idosos com FA.

Abstract Background There are no randomized studies comparing the maintenance of sinus rhythm after catheter ablation (CA) concerning treatment with antiarrhythmic drugs (AA) in elderly patients with paroxysmal atrial fibrillation (AF). Objectives To compare the clinical results of pulmonary vein (PV) isolation with the second-generation PVAC Gold catheter against AA treatment in elderly people with recurrent symptomatic paroxysmal AF, refractory to at least one AA, and without structural heart disease. Methods Sixty patients with paroxysmal AF ≥ 65 years old were randomized to two forms of treatment: group 1: CA and group 2: AA drugs. The primary outcome was the AF recurrence-free rate after at least one year of follow-up. Secondary outcomes were: progression to persistent forms of AF, impact on quality of life (QOLF), and complications. The significance level adopted in the statistical analysis was 5% (p<0.05). Results The AF recurrence-free rate was 80% (10% with amiodarone) in the CA group, after 1.3 procedures per patient and 65% in the AA group (60% with amiodarone), (p = 0.119) in an average follow-up of 719 days (Q1: 566; Q3: 730). The persistent AF free rate was 83.4% in the AC group and 67.7% in the AA group (p = 0.073) Both strategies showed an improvement in the AFQoL score during follow-up (p < 0.001), with no difference between the groups. Although without clinical repercussions or impact on the intellectual assessment test, 25% of patients in the CA group showed signs of cerebral embolization on brain MRI. Conclusions Both strategies for maintaining sinus rhythm promoted an improvement in the quality of life of elderly patients with symptomatic AF, with no statistical difference in the clinical outcomes. Additional studies using technologies with a better safety profile are needed to evaluate the benefits of CA in elderly patients with AF.

[Quality of life in patients with idiopathic ventricular arrhythmias treated at the Instituto Nacional Cardiovascular - INCOR]. / Calidad de vida en pacientes con arritmias ventriculares idiopáticas tratados en el Instituto Nacional Cardiovascular - INCOR.

Objective: To describe the quality of life in patients with idiopathic ventricular arrhythmias treated at the Instituto Nacional Cardiovascular INCOR in Lima -Peru. Materials and methods: . Analytical and cross-sectional study of patients with idiopathic ventricular arrhythmias treated by 3D ablation or antiarrhythmic therapy between July 2017 and December 2019 to whom the SF-36 health questionnaire was applied to assess quality of life related to health. Results: Fifty-two patients with idiopathic ventricular arrhythmias were included (34 underwent 3D ablation, and 18 underwent antiarrhythmic therapy only). The percentage of recurrence (14.7% vs. 50%, p=0.01) and adverse effects (0% vs. 22.2%, p=0.011) were lower in the 3D ablation group compared to the antiarrhythmic group. The mean standardized scores obtained from the Spanish version of the Health Survey SF-36v2, applied to the 3D ablation and antiarrhythmic groups were 85.1 vs 68.4 (p<0.001), respectively. Were found statistically significant differences in 6 of the eight components that evaluate health-related quality of life: physical function (96.0 vs. 76.0, p<0.001), physical role (93.4 vs. 61.1, p<0.001), general health (74.5 vs. 47.4, p<0.001), vitality (69.9 vs 54.7, p=0.008), emotional role (92.2 vs. 77.8, p=0.006) and mental health (73.8 vs. 60, p<0.001). Conclusions: Patients with idiopathic ventricular arrhythmias who underwent 3D ablation have a higher mean standardized score for health-related quality of life.

Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells.

Voltage-dependent K+ (Kv) channels are widely expressed on vascular smooth muscle cells and regulate vascular tone. Here, we explored the inhibitory effect of encainide, a class Ic anti-arrhythmic agent, on Kv channels of vascular smooth muscle from rabbit coronary arteries. Encainide inhibited Kv channels in a concentration-dependent manner with an IC50 value of 8.91 ± 1.75 µM and Hill coefficient of 0.72 ± 0.06. The application of encainide shifted the activation curve toward a more positive potential without modifying the inactivation curve, suggesting that encainide inhibited Kv channels by altering the gating property of channel activation. The inhibition by encainide was not significantly affected by train pulses (1 and 2 Hz), indicating that the inhibition is not use (state)-dependent. The inhibitory effect of encainide was reduced by pretreatment with the Kv1.5 subtype inhibitor. However, pretreatment with the Kv2.1 subtype inhibitor did not alter the inhibitory effects of encainide on Kv currents. Based on these results, encainide inhibits vascular Kv channels in a concentration-dependent and use (state)-independent manner by altering the voltage sensor of the channels. Furthermore, Kv1.5 is the main Kv subtype involved in the effect of encainide.

Antiarrhythmic Effect of Artemisinin in an Ex-vivo Model of Brugada Syndrome Induced by NS5806.

BACKGROUND AND OBJECTIVES: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (Ito) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of Ito channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. METHODS: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 µM), calcium channel blocker verapamil (1 µM), and Ito agonist NS5806 (6-10 µM) were used. Artemisinin (100-150 µM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. RESULTS: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. CONCLUSIONS: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including Ito channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

Prevalence and bleeding risk associated with the concomitant use of direct oral anticoagulants and antiarrhythmic drugs in patients with atrial fibrillation, based on the French healthcare insurance database.

PURPOSE: Pharmacokinetic interactions exist between apixaban or rivaroxaban, and CYP3A4 and P-glycoprotein inhibitors such as amiodarone, verapamil and diltiazem. We aimed to estimate the prevalence of exposure to this drug-drug association (DDA) and to assess the bleeding risk associated in patients with atrial fibrillation (AF). METHODS: We conducted a cohort study using a representative 1/97th sample of the French healthcare insurance database between 2014 and 2019. Patients with AF receiving apixaban or rivaroxaban were included and followed-up until hospitalization for bleeding, death, discontinuation of apixaban or rivaroxaban, exposure to strong CYP3A4 inhibitor, or until December 31st 2019, whichever came first. Primary outcome was hospitalization for bleeding registered as primary diagnosis. The association between the exposure to the DDA and hospitalization for bleeding was evaluated as a time-dependent variable in Cox model. RESULTS: Between 2014 and 2019, the AF population under apixaban or rivaroxaban represented 10,392 patients. During the study period, the annual average prevalence of DDA exposure in this population was 38.9%. Among the 10,392 patients, 223 (2.1%) were hospitalized for bleeding, of which 75 (33.6%) received the association and 148 (66.4%) received apixaban or rivaroxaban alone. There was no association between DDA exposure and risk of hospitalization for bleeding (aHR = 1.19, [95% CI: 0.90, 1.58]). Age (HR 1.03 [1.02, 1.05]) and male gender (HR 1.72 [1.28, 2.30]) were associated with an increased risk of hospitalization for bleeding. CONCLUSION: Exposure to antiarrhythmic drugs was not associated with an increased risk of hospitalization for bleeding in patients with AF under rivaroxaban or apixaban.

Long-term safety and efficacy of renal sympathetic denervation in atrial fibrillation: 3-year results of the AFFORD study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia which has been associated with increased sympathetic nervous system activity and hypertension. Recent evidence indicated that renal sympathetic denervation (RDN) could safely contribute to an improvement in AF burden. OBJECTIVE: To investigate the long-term safety and efficacy of radiofrequency RDN in hypertensive patients with symptomatic AF. METHODS: This pilot study included patients with symptomatic paroxysmal or persistent AF (European Hearth Rhythm Association class ≥ II) despite optimal medical therapy, office systolic blood pressure (BP) ≥ 140 mmHg and ≥ 2 antihypertensive drugs. AF burden was measured using an implantable cardiac monitor (ICM), implanted 3 months prior to RDN. ICM interrogation and 24-h ambulatory BP monitoring were performed at baseline and at 3/6/12/24/36 months post RDN. The primary efficacy outcome was daily AF burden. Statistical analyses were performed using Poisson and negative binomial models. RESULTS: A total of 20 patients with a median age [25th-75th percentiles] of 66.2 [61.2-70.8] years (55% female) were included. At baseline, office BP ± standard deviation (SD) was 153.8/87.5 ± 15.2/10.4 mmHg, while mean 24-h ambulatory BP was 129.5/77.3 ± 15.5/9.3 mmHg. Baseline daily AF burden was 1.4 [0.0-10.9] minutes/day and throughout a 3-year follow-up period, no significant change was observed (- 15.4%/year; 95% confidence interval (CI) - 50.2%, + 43.7%; p = 0.54). The number of defined daily doses of antiarrhythmic drugs and antihypertensive drugs remained stable over time, while mean 24-h ambulatory systolic BP decreased with - 2.2 (95% CI - 3.9, - 0.6; p = 0.01) mmHg/year. CONCLUSIONS: In patients with hypertension and symptomatic AF, stand-alone RDN reduced BP but did not significantly reduce AF burden up until 3 years of follow-up.

Pathophysiology and treatment of adults with arrhythmias in the emergency department, part 1: Atrial arrhythmias.

PURPOSE: This article, the first in a 2-part review, aims to reinforce current literature on the pathophysiology of cardiac arrhythmias and various evidence-based treatment approaches and clinical considerations in the acute care setting. Part 1 of this series focuses on atrial arrhythmias. SUMMARY: Arrhythmias are prevalent throughout the world and a common presenting condition in the emergency department (ED) setting. Atrial fibrillation (AF) is the most common arrhythmia worldwide and expected to increase in prevalence. Treatment approaches have evolved over time with advances in catheter-directed ablation. Based on historic trials, heart rate control has been the long-standing accepted outpatient treatment modality for AF, but the use of antiarrhythmics is often still indicated for AF in the acute setting, and ED pharmacists should be prepared and poised to help in AF management. Other atrial arrhythmias include atrial flutter (AFL), atrioventricular nodal reentry tachycardia (AVNRT), and atrioventricular reentrant tachycardia (AVRT), which warrant distinction due to their unique pathophysiology and because each requires a different approach to utilization of antiarrhythmics. Atrial arrhythmias are typically associated with greater hemodynamic stability than ventricular arrhythmias but still require nuanced management according to patient subset and risk factors. Since antiarrhythmics can also be proarrhythmic, they may destabilize the patient due to adverse effects, many of which are the focus of black-box label warnings that can be overreaching and limit treatment options. Electrical cardioversion for atrial arrhythmias is generally successful and, depending on the setting and/or hemodynamics, often indicated. CONCLUSION: Atrial arrhythmias arise from a variety of mechanisms, and appropriate treatment depends on various factors. A firm understanding of physiological and pharmacological concepts serves as a foundation for exploring evidence supporting agents, indications, and adverse effects in order to provide appropriate care for patients.

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.

Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden.

BACKGROUND: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial-Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known. METHODS: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA2DS2-VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA2DS2-VA score). RESULTS: EAST-AFNET4 randomized 1093 patients with CHA2DS2-VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA2DS2-VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA2DS2-VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51-0.81]; P < 0.001) but not in patients with CHA2DS2-VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73-1.19]; P=0.56, Pinteraction=0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA2DS2-VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P=0.175), but occurred more often in patients with CHA2DS2-VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05-1.82]; P=0.019, Pinteraction=0.008). Life-threatening events or death were not different between groups (CHA2DS2-VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA2DS2-VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA2DS2-VA score), the Pinteraction was not significant for the primary efficacy outcome (P=0.25), but remained significant (P=0.044) for the primary safety outcome. CONCLUSIONS: Patients with recently diagnosed atrial fibrillation and CHA2DS2-VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01288352. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20. URL: https://www.isrctn.com/; Unique identifier: ISRCTN04708680.

Effective Control of Supraventricular Tachycardia in Neonates May Requires Combination Pharmacologic Therapy.

INTRODUCTION: Supraventricular tachycardia (SVT) is one of the arrhythmias that can occur in newborns. Most SVT incidents in the neonatal period are spontaneously resolved around the first year of life, but since tachycardia can frequently occur before complete resolution, appropriate medication use is required. However, no clear guidelines or consensus on the treatment of neonatal SVT have been established yet. METHODS: From January 2011 to December 2021, demographic data and antiarrhythmic medications used were retrospectively analyzed for 18 newborns diagnosed with SVT at a single center. RESULTS: A total of four medications (propranolol, amiodarone, flecainide, and atenolol) were used as maintenance therapy to prevent tachycardia recurrence, and propranolol was the most used, followed by amiodarone. Thirty-nine percent of the patients were controlled with monotherapy, but the remainder required two or more medications. The median period from medication initiation after diagnosis to the last tachycardia event was 15.5 days, and the median total duration of medication use was 362 days. None of the patients experienced any side effects of antiarrhythmic medications. The total duration of medication use was statistically significant according to the mechanism of SVT, and the usage time of the increased automaticity group was shorter than that of the re-entry group. CONCLUSION: Since most neonatal SVT resolves within 1 year, it is significant to provide prophylactic medication to prevent tachycardia recurrence at least until 1 year of age, and depending on the patient, the appropriate combination of medications should be identified.

Cost-Effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation: The CABANA Randomized Clinical Trial.

BACKGROUND: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point. METHODS: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D-based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective. RESULTS: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360-$27 170) and the lifetime mean cost difference was $15 516 (95% CI, -$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio <$100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained. CONCLUSIONS: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

Drug Interactions Affecting Antiarrhythmic Drug Use.

Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.

Continuous Thoracic Paravertebral Block to Treat Electrical Storm.

Continuous ganglion block is increasingly being used to help manage ventricular tachyarrhythmias. We present the cases of 2 patients in whom we used continuous left thoracic paravertebral block to achieve sympathetic denervation and improvement in drug-refractory ventricular tachyarrhythmias. Whether as destination therapy or bridging therapy, we conclude that the block is safe, improves patients' comfort, and is superior in several ways to stellate ganglion block and other single-injection techniques.

Diagnostic lacunae and implications of an automated implantable cardioverter defibrillator implantation in a child with type 3 Long QT (LQT3) syndrome.

A diagnosis of congenital long QT interval syndrome based on history and electrocardiogram was made in a child in the absence of readily available genetic testing. A genotype 3 (LQT3) was suspected after exclusion of other variants as the child was non-responsive to beta-blocker and sodium channel blocker medication. As the child continues to show episodic bradycardia, polymorphic ventricular ectopy, and T-wave alternans, a single-chamber automated implantable cardioverter-defibrillator implantation was done successfully. This report highlights how the diagnosis of LQT3 was arrived at as well as the anesthetic challenges in the management of patients with LQTS.

Ablação por Cateter é Superior a Drogas Antiarrítmicas como Tratamento de primeira linha para Fibrilação Atrial: uma Revisão Sistemática e Metanálise / Catheter Ablation is Superior to Antiarrhythmic Drugs as First-Line Treatment for Atrial Fibrillation: a Systematic Review and Meta-Analysis

Resumo Fundamento A ablação por cateter é uma terapia bem estabelecida para controle do ritmo cardíaco em pacientes refratários ou intolerantes a drogas antiarrítmicas (DAA). Porém, a eficácia desse procedimento comparada à de DAA como estratégia de primeira linha no controle do ritmo cardíaco na fibrilação atrial é menos conhecida. Objetivos Conduzir uma revisão sistemática e metanálise da ablação por cateter vs. DAA em pacientes sem nenhum tratamento prévio para controle do ritmo. Métodos Buscamos, nos bancos de dados do PubMed, EMBASE, e Cochrane, ensaios randomizados controlados que compararam ablação por cateter com DAA para controle do ritmo cardíaco em pacientes com FA sintomática e descreveram os seguintes desfechos: (1) recorrência de taquiarritmia atrial (TA); (2) FA sintomática; (3) internações hospitalares; e (4) bradicardia sintomática. A heterogeneidade foi avaliada por estatística I2. Valores de p menores que 0,05 foram considerados estatisticamente significativos. Resultados Incluímos cinco ensaios com 994 pacientes, dos quais 502 (50,5%) foram submetidos à ablação por cateter. O período médio de acompanhamento foi de um a cinco anos. Recorrências de TA (OR 0,36; IC95% 0,25-0,52; p<0,001) e de FA sintomática (OR 0,32; IC95% 0,18-0,57; p<0,001), e internações hospitalares (OR 0,25; IC95% 0,15-0,42; p<0,001) foram menos frequentes nos pacientes tratados com ablação por cateter que naqueles tratados com DAA. Bradicardia sintomática não foi diferente entre os grupos (OR 0,55; IC95% 0,18-1,65; p=0,28). Derrame ou tamponamento pericárdico significativo ocorreu em oito dos 464 (1,7%) pacientes no grupo submetido à ablação. Conclusão Esses achados sugerem maior eficácia da ablação por cateter que das DAA como estratégia inicial de controle do ritmo cardíaco em pacientes com DA sintomática.

Abstract Background Catheter ablation is a well-established therapy for rhythm control in patients who are refractory or intolerant to anti-arrhythmic drugs (AAD). Less is known about the efficacy of catheter ablation compared with AAD as a first-line strategy for rhythm control in atrial fibrillation (AF). Objectives We aimed to perform a systematic review and meta-analysis of catheter ablation vs. AAD in patients naïve to prior rhythm control therapies. Methods PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials that compared catheter ablation to AAD for initial rhythm control in symptomatic AF and reported the outcomes of (1) recurrent atrial tachyarrhythmias (ATs); (2) symptomatic AF; (3) hospitalizations; and (4) symptomatic bradycardia. Heterogeneity was examined with I2statistics. P values of < 0.05 were considered statistically significant. Results We included five trials with 994 patients, of whom 502 (50.5%) underwent catheter ablation. Mean follow-up ranged from one to five years. Recurrences of AT (OR 0.36; 95% CI 0.25-0.52; p<0.001) and symptomatic AF (OR 0.32; 95% CI 0.18-0.57; p<0.001), and hospitalizations (OR 0.25; 95% CI 0.15-0.42; p<0.001) were significantly less frequent in patients treated with catheter ablation compared with AAD. Symptomatic bradycardia was not significantly different between groups (OR 0.55; 95% CI 0.18-1.65; p=0.28). Significant pericardial effusions or tamponade occurred in eight of 464 (1.7%) patients in the catheter ablation group. Conclusion These findings suggest that catheter ablation has superior efficacy to AAD as an initial rhythm control strategy in patients with symptomatic AF.

Nifekalant versus Amiodarone for Out-Of-Hospital Cardiac Arrest with Refractory Shockable Rhythms; a Post Hoc Analysis.

INTRODUCTION: It is still unclear that which anti-arrhythmics are adequate for treating refractory dysrhythmia. This study aimed to compare amiodarone and nifekalant in management of out-of-hospital cardiac arrest cases with refractory shockable rhythm. METHODS: This was a post hoc analysis of cases registered in a nationwide, multicentre, prospective registry that includes 288 critical care medical centres in Japan. From June 2014 to December 2017, we included all out-of-hospital cardiac arrest patients aged ≥18 years who presented with refractory arrhythmia (sustained ventricular fibrillation or ventricular tachycardia following delivery of at least two defibrillator shocks) and treated with nifekalant or amiodarone after arrival to hospital. Overlap weight was performed to address potential confounding factors. RESULTS: 1,317 out-of-hospital cardiac arrest patients with refractory arrhythmia were enrolled and categorized into amiodarone (n = 1,275) and nifekalant (n = 42) groups. After overlap weight was performed, there were no significant intergroup differences in increased the rate of admission after return of spontaneous circulation [-5.9% (95%CI: -7.1 to 22.4); p = 0.57], 30-day favourable neurological outcome [0.1% (95%CI: -14 to 13.9); p = 0.99], and 30-day survival [-3.9% (95% CI: -19.8 to 12.0); p = 0.63]. CONCLUSION: This nationwide study showed that nifekalant was not associated with improved outcomes regarding admission after return of spontaneous circulation, 30-day survival, and 30-day favourable neurological outcome compared with amiodarone.