External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Practical approach for atrial cardiomyopathy characterization in patients with atrial fibrillation.

Atrial fibrillation (AF) causes progressive structural and electrical changes in the atria that can be summarized within the general concept of atrial remodeling. In parallel, other clinical characteristics and comorbidities may also affect atrial tissue properties and make the atria susceptible to AF initiation and its long-term persistence. Overall, pathological atrial changes lead to atrial cardiomyopathy with important implications for rhythm control. Although there is general agreement on the role of the atrial substrate for successful rhythm control in AF, the current classification oversimplifies clinical management. The classification uses temporal criteria and does not establish a well-defined strategy to characterize the individual-specific degree of atrial cardiomyopathy. Better characterization of atrial cardiomyopathy may improve the decision-making process on the most appropriate therapeutic option. We review current scientific evidence and propose a practical characterization of the atrial substrate based on 3 evaluation steps starting with a clinical evaluation (step 1), then assess outpatient complementary data (step 2), and finally include information from advanced diagnostic tools (step 3). The information from each of the steps or a combination thereof can be used to classify AF patients in 4 stages of atrial cardiomyopathy, which we also use to estimate the success on effective rhythm control.

Hemodynamic Effects of the Osmopressor Response: A Systematic Review and Meta-Analysis.

Background Rapidly consuming water may offer practical orthostatic hypotension therapy. However, its efficacy across disorders remains uncertain. This study aims to assess the impact of rapid 350- to 500-mL water intake on systolic and diastolic blood pressure (BP) and heart rate (HR) through a systematic review and meta-analysis. Methods and Results We systematically reviewed MEDLINE and Embase up to June 2023, including randomized controlled trials and prospective cohort studies. Using random-effects meta-analysis, we calculated pooled mean differences (MDs) for maximum hemodynamic effects of rapid 350- to 500-mL water bolus consumption. Participants with orthostatic hypotension experienced increased systolic BP (MD, 24.18 [95% CI, 15.48-32.88]) and diastolic BP (MD, 11.98 [95% CI, 8.87-15.09]) with decreased HR (MD, -3.46 [95% CI, -5.21 to -1.71]). Similar results were observed in multiple system atrophy and pure autonomic failure subgroup analysis. Healthy participants showed modest increases in systolic BP (MD, 2.33 [95% CI, 1.02-3.64]) and diastolic BP (MD, 2.73 [95% CI, 1.15-4.30]), but HR changes were not significant (MD, -2.06 [95% CI, -5.25 to 1.13]). Water had no significant hemodynamic effects in patients with seated or supine postural tachycardia syndrome, although standing effects were unassessed. Our data do not exclude water's potential standing effect in postural tachycardia syndrome. Conclusions In patients with orthostatic hypotension, rapid water intake elevated short-term systolic BP and diastolic BP, with mild HR reduction when seated or supine. Healthy participants exhibited similar but milder effects. However, patients with postural tachycardia syndrome did not experience these changes in seated or supine positions. Further research is needed to evaluate the promising impact of rapid water ingestion on patients with postural tachycardia syndrome in a standing position, which was not addressed in our study.

Standard vs Augmented Ablation of Paroxysmal Atrial Fibrillation for Reduction of Atrial Fibrillation Recurrence: The AWARE Randomized Clinical Trial.

Importance: Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs. Objective: To evaluate the superiority of an augmented double wide-area circumferential ablation (WACA) compared with a standard single WACA in preventing recurrent atrial arrhythmias (AA) (atrial tachycardia, atrial flutter, or atrial fibrillation [AF]) in patients with paroxysmal AF. Design, Setting, and Participants: This was a pragmatic, multicenter, prospective, randomized, open, blinded end point superiority clinical trial conducted at 10 university-affiliated centers in Canada. The trial enrolled patients 18 years and older with symptomatic paroxysmal AF from March 2015 to May 2017. Analysis took place between January and April 2022. Analyses were intention to treat. Interventions: Patients were randomized (1:1) to receive radiofrequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA. Main Outcomes and Measures: The primary outcome was AA recurrence between 91 and 365 days postablation. Patients underwent 42 days of ambulatory electrocardiography monitoring after ablation. Secondary outcomes included need for repeated catheter ablation and procedural and safety variables. Results: Of 398 patients, 195 were randomized to the single WACA (control) arm (mean [SD] age, 60.6 [9.3] years; 65 [33.3%] female) and 203 to the double WACA (experimental) arm (mean [SD] age, 61.5 [9.3] years; 66 [32.5%] female). Overall, 52 patients (26.7%) in the single WACA arm and 50 patients (24.6%) in the double WACA arm had recurrent AA at 1 year (relative risk, 0.92; 95% CI, 0.66-1.29; P = .64). Twenty patients (10.3%) in the single WACA arm and 15 patients (7.4%) in the double WACA arm underwent repeated catheter ablation (relative risk, 0.72; 95% CI, 0.38-1.36). Adjudicated serious adverse events occurred in 13 patients (6.7%) in the single WACA arm and 14 patients (6.9%) in the double WACA arm. Conclusions and Relevance: In this randomized clinical trial of patients with paroxysmal AF, additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set. Trial Registration: ClinicalTrials.gov Identifier: NCT02150902.

Objective Hemodynamic Cardiovascular Autonomic Abnormalities in Post-Acute Sequelae of COVID-19.

BACKGROUND: Many COVID-19 patients are left with symptoms several months after resolution of the acute illness; this syndrome is known as post-acute sequalae of COVID-19 (PASC). We aimed to determine the prevalence of objective hemodynamic cardiovascular autonomic abnormalities (CAA), explore sex differences, and assess the prevalence of CAA among hospitalized vs nonhospitalized patients with PASC. METHODS: Patients with PASC (n = 70; female [F] = 56; 42 years of age; 95% confidence interval [CI], 40-48) completed standard autonomic tests, including an active stand test 399 days (338, 455) after their COVID-19 infection. Clinical autonomic abnormalities were evaluated. RESULTS: Most patients with PASC met the criteria for at least 1 CAA (51; 73%; F = 43). The postural orthostatic tachycardia syndrome hemodynamic (POTSHR) criterion of a heart rate increase of > 30 beats per minute within 5 to 10 minutes of standing was seen in 21 patients (30%; F = 20; P = 0.037 [by sex]). The initial orthostatic hypotension hemodynamic (IOH40) criterion of a transient systolic blood pressure change of > 40 mm Hg in the first 15 seconds of standing was seen in 43 (61%) patients and equally among female and male patients (63% vs 57%; P = 0.7). Only 9 (13%) patients were hospitalized; hospitalized vs nonhospitalized patients had similar frequencies of abnormalities (67% vs 74%; P = 0.7). CONCLUSIONS: Patients with PASC have evidence of CAA, most commonly IOH40, which will be missed unless an active stand test is used. Female patients have increased frequency of POTSHR, but IOH40 is equally prevalent between sexes. Finally, even nonhospitalized "mild" infections can result in long-term CAAs.

Machine learning for atrial fibrillation risk prediction in patients with sleep apnea and coronary artery disease.

Background: Patients with sleep apnea (SA) and coronary artery disease (CAD) are at higher risk of atrial fibrillation (AF) than the general population. Our objectives were: to evaluate the role of CAD and SA in determining AF risk through cluster and survival analysis, and to develop a risk model for predicting AF. Methods: Electronic medical record (EMR) database from 22,302 individuals including 10,202 individuals with AF, CAD, and SA, and 12,100 individuals without these diseases were analyzed using K-means clustering technique; k-nearest neighbor (kNN) algorithm and survival analysis. Age, sex, and diseases developed for each individual during 9 years were used for cluster and survival analysis. Results: The risk models for AF, CAD, and SA were identified with high accuracy and sensitivity (0.98). Cluster analysis showed that CAD and high blood pressure (HBP) are the most prevalent diseases in the AF group, HBP is the most prevalent disease in CAD; and HBP and CAD are the most prevalent diseases in the SA group. Survival analysis demonstrated that individuals with HBP, CAD, and SA had a 1.5-fold increased risk of developing AF [hazard ratio (HR): 1.49, 95% CI: 1.18-1.87, p = 0.0041; HR: 1.46, 95% CI: 1.09-1.96, p = 0.01; HR: 1.54, 95% CI: 1.22-1.94, p = 0.0039, respectively] and individuals with chronic kidney disease (CKD) developed AF approximately 50% earlier than patients without these comorbidities in a period of 7 years (HR: 3.36, 95% CI: 1.46-7.73, p = 0.0023). Comorbidities that contributed to develop AF earlier in females compared to males in the group of 50-64 years were HBP (HR: 3.75 95% CI: 1.08-13, p = 0.04) CAD and SA in the group of 60-75 years were (HR: 2.4 95% CI: 1.18-4.86, p = 0.02; HR: 2.51, 95% CI: 1.14-5.52, p = 0.02, respectively). Conclusion: Machine learning based algorithms demonstrated that CAD, SA, HBP, and CKD are significant risk factors for developing AF in a Latin-American population.

Machine learning prediction of atrial fibrillation in cardiovascular patients using cardiac magnetic resonance and electronic health information.

Background: Atrial fibrillation (AF) is a commonly encountered cardiac arrhythmia associated with morbidity and substantial healthcare costs. While patients with cardiovascular disease experience the greatest risk of new-onset AF, no risk model has been developed to predict AF occurrence in this population. We hypothesized that a patient-specific model could be delivered using cardiovascular magnetic resonance (CMR) disease phenotyping, contextual patient health information, and machine learning. Methods: Nine thousand four hundred forty-eight patients referred for CMR imaging were enrolled and followed over a 5-year period. Seven thousand, six hundred thirty-nine had no prior history of AF and were eligible to train and validate machine learning algorithms. Random survival forests (RSFs) were used to predict new-onset AF and compared to Cox proportional-hazard (CPH) models. The best performing features were identified from 115 variables sourced from three data domains: (i) CMR-based disease phenotype, (ii) patient health questionnaire, and (iii) electronic health records. We evaluated discriminative performance of optimized models using C-index and time-dependent AUC (tAUC). Results: A RSF-based model of 20 variables (CIROC-AF-20) delivered an overall C-index of 0.78 for the prediction of new-onset AF with respective tAUCs of 0.80, 0.79, and 0.78 at 1-, 2- and 3-years. This outperformed a novel CPH-based model and historic AF risk scores. At 1-year of follow-up, validation cohort patients classified as high-risk of future AF by CIROC-AF-20 went on to experience a 17.3% incidence of new-onset AF, being 24.7-fold higher risk than low risk patients. Conclusions: Using phenotypic data available at time of CMR imaging we developed and validated the first described risk model for the prediction of new-onset AF in patients with cardiovascular disease. Complementary value was provided by variables from patient-reported measures of health and the electronic health record, illustrating the value of multi-domain phenotypic data for the prediction of AF.

A Cost-Utility Analysis of the Syncope: Pacing or Recording in The Later Years (SPRITELY) Trial.

Background: The Syncope: Pacing or Recording in the Later Years (SPRITELY) trial reported that a strategy of empiric permanent pacing in patients with syncope and bifascicular block reduces major adverse events more effectively than acting on the results of an implantable cardiac monitor (ICM). Our objective was to determine the cost-effectiveness of using the ICM, compared with a pacemaker (PM), in the management of older adults (age > 50 years) with bifascicular block and syncope enrolled in the SPRITELY trial. Methods: SPRITELY was a pragmatic, open-label randomized controlled trial with a median follow-up of 33 months. The primary outcome of this analysis is the cost per additional quality-adjusted life-year (QALY). Resource utilization and utility data were collected prospectively, and outcomes at 2 years were compared between the 2 arms. A decision analytic model simulated a 3-year time horizon. Results: The mean cost incurred by participants randomized to the PM arm was $9918, compared to $15,416 (both in Canadian dollars) for participants randomized to the ICM arm. The ICM strategy resulted in 0.167 QALYs fewer than the PM strategy. Cost and QALY outcomes are sensitive to the proportion of participants randomized to the ICM arm who subsequently required PM insertion. In 40,000 iterations of probabilistic sensitivity analysis, the PM strategy resulted in cost-savings in 99.7% of iterations, compared with the ICM strategy. Conclusions: The PM strategy was dominant-that is, less costly and estimated to result in a greater number of QALYs. For patients with unexplained syncope, bifascicular block, and age > 50 years, a PM is more likely to be cost-effective than an ICM.

Contexte: L'essai SPRITELY ( S yncope: P acing or R ecording i n t h e L ater Y ears) a été mené auprès de patients ayant subi une syncope et un bloc bifasciculaire. Elle a montré qu'une méthode de stimulation électrique permanente et empirique du cœur permet de réduire les événements indésirables majeurs plus efficacement qu'une méthode reposant sur les résultats d'un moniteur cardiaque implantable. Notre objectif était de déterminer le rapport coût-efficacité de l'utilisation du moniteur cardiaque implantable par rapport à un stimulateur cardiaque dans la prise en charge de personnes âgées de plus de 50 ans présentant un bloc bifasciculaire et une syncope, inscrits à l'essai SPRITELY. Méthodologie: SPRITELY était un essai contrôlé ouvert et pragmatique à répartition aléatoire, dont le suivi médian était de 33 mois. Le paramètre d'évaluation principal de cette analyse était le coût supplémentaire par année de vie ajustée en fonction de la qualité (AVAQ). Les données sur l'utilisation des ressources et l'utilité ont été recueillies de manière prospective, et les résultats à deux ans ont été comparés entre les deux groupes. Un modèle décisionnel analytique a été utilisé pour simuler un horizon temporel de trois ans. Résultats: Le coût moyen pour les participants répartis aléatoirement dans le groupe utilisant un stimulateur cardiaque était de 9 918 $ CAN comparativement à 15 416 $ CAN pour ceux utilisant un moniteur cardiaque implantable. La stratégie du moniteur cardiaque implantable s'est traduite par une réduction de 0,167 du nombre d'AVAQ par rapport à la stratégie reposant sur le stimulateur cardiaque. Les résultats relatifs aux coûts et aux AVAQ sont sensibles à la proportion de participants répartis aléatoirement dans le groupe du moniteur cardiaque implantable qui ont par la suite dû recevoir un stimulateur cardiaque. Sur 40 000 itérations de l'analyse de sensibilité probabiliste, la stratégie du stimulateur cardiaque a occasionné des économies dans 99,7 % des itérations comparativement à la stratégie du moniteur cardiaque implantable. Conclusions: La stratégie du stimulateur cardiaque était dominante, autrement dit moins coûteuse et, selon les estimations, entraînerait un plus grand nombre d'AVAQ. Pour les patients de plus de 50 ans présentant une syncope idiopathique et un bloc bifasciculaire, un stimulateur cardiaque est plus susceptible d'être moins coûteux qu'un moniteur cardiaque implantable.

Pacing for vasovagal syncope: Tips for use in practice.

Vasovagal syncope (VVS) continues to be the most frequent cause of syncope in all age groups. Recent randomized double-blinded trials (RCTs) provide further support for pacing in selected cases of patients with recurrent refractory VVS with significant cardio-inhibitory response either documented spontaneously or induced during head-up tilt testing (HUTT). Cardiac pacing is the only therapy of proven efficacy for the predominant cardio-inhibitory phenotype of vasovagal (reflex) syncope; however, several questions regarding the best candidates remain. The current review focuses on practical tips for use of cardiac pacing in practice.

Cardioneuroablation for vasovagal syncope: A systematic review and meta-analysis.

BACKGROUND: Cardioneuroablation (CNA) has emerged as promising therapy for patients with refractory vasovagal syncope (VVS). OBJECTIVE: The purpose of this study was to provide a freedom from syncope estimate for CNA, including subgroup analysis by method and target of ablation. METHODS: A systematic search was performed in MEDLINE and EMBASE according to the PRISMA guidelines until February 14, 2022. Observational studies and clinical trials reporting freedom from syncope were included. Meta-analysis was performed with a random-effects model. RESULTS: A total of 465 patients were included across 14 studies (mean age 39.8 ± 4.0 year; 53.5% female). Different techniques were used to guide CNA: 50 patients (10.8%) by mapping fractionated electrograms, 73 (15.7%) with the spectral method, 210 (45.2%) with high-frequency stimulation, 73 (15.7%) with a purely anatomically guided method, and 59 (12.6%) with a combination. The target was biatrial in 168 patients (36.1%), left atrium only in 259 (55.7%), and right atrium only in 38 (8.2%). The freedom from syncope was 91.9% (95% confidence interval [CI] 88.1%-94.6%; I2 = 6.9%; P = .376). CNA limited to right atrial ablation was associated with a significant lower freedom from syncope (81.5%; 95% CI 51.9%-94.7%; P <.0001) vs left atrial ablation only (94.0%; 95% CI 88.6%--6.9%) and biatrial ablation (92.7%; 95% CI 86.8%-96.1%). Subgroup analysis according to the technique used to identify ganglionated plexi did not show any significant difference in freedom from syncope (P = .206). CONCLUSION: This meta-analysis suggests a high freedom from syncope after CNA in VVS. Well-designed, double-blind, multicenter, sham-controlled randomized clinical trials are needed to provide evidence for future guidelines.

Cardioneuroablation for vasovagal syncope and atrioventricular block: A step-by-step guide.

Catheter-based cardioneuroablation is increasingly being utilized to improve outcomes in patients with vasovagal syncope and atrioventricular block due to vagal hyperactivity. There is now increasing convergence among enthusiasts on its various aspects, including patient selection, technical steps, and procedural end-points. This pragmatic review aims to take the reader through a step-by-step approach to cardioneuroablation: we begin with a brief overview of the anatomy of intrinsic cardiac autonomic nervous system, before focusing on the indications, preprocedure and postprocedure management, necessary equipment, and its potential limitations.