Rhythm vs Rate Control Strategy for Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Rhythm control, either with antiarrhythmic drugs or catheter ablation, and rate control strategies are the cornerstones of atrial fibrillation (AF) management. Despite the increasing role of rhythm control over the past few years, it remains inconclusive which strategy is superior in improving clinical outcomes. OBJECTIVES: This study summarizes the total and time-varying evidence regarding the efficacy of rhythm- vs rate-control strategies in the management of AF. METHODS: We systematically perused the MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases for randomized controlled trials from inception to November 2023. We included studies that compared the efficacy of rhythm control (ie, antiarrhythmic drugs classes Ia, Ic, or III, AF catheter ablation, and electrical cardioversion) and rate control (ie, beta-blocker, digitalis, or calcium antagonist) strategies among patients with nonvalvular AF. The primary outcome was cardiovascular (CV) death, whereas secondary outcomes included all-cause death, stroke, hospitalization for heart failure (HF), sinus rhythm at the end of the follow-up, and rhythm control-related adverse events. A cumulative meta-analysis to assess temporal trends and a meta-regression analysis using the percentage of ablation use was performed. RESULTS: We identified 18 studies with a total of 17,536 patients (mean age: 68.6 ± 9.7 years, 37.9% females) and a mean follow-up of 28.5 months. Of those, 31.9% had paroxysmal AF. A rhythm control strategy reduced CV death (HR: 0.78; 95% CI: 0.62-0.96), stroke (HR: 0.801; 95% CI: 0.643-0.998), and hospitalization for HF (HR: 0.80; 95% CI: 0.69-0.94) but not all-cause death (HR: 0.86; 95% CI: 0.73-1.02) compared with a rate control strategy. This benefit was driven by contemporary studies, whereas more ablation use within the rhythm control arm was associated with improved outcomes, except stroke. CONCLUSIONS: In patients with AF, a contemporary rhythm control strategy leads to reduced CV mortality, HF events, and stroke compared with a rate control strategy.

Interventional management of mitral regurgitation and sleep disordered breathing: "Catching two birds with one stone".

Sleep disordered breathing (SDB), mostly constituting of obstructive and central sleep apnea (OSA and CSA, respectively), is highly prevalent in the general population, and even more among patients with cardiovascular disease, heart failure (HF) and valvular heart disease, such as mitral regurgitation (MR). The coexistence of HF, MR and SDB is associated with worse cardiovascular outcomes and increased morbidity and mortality. Pulmonary congestion, as a result of MR, can exaggerate and worsen the clinical status and symptoms of SDB, while OSA and CSA, through various mechanisms that impair left ventricular dynamics, can promote left ventricular remodelling, mitral annulus dilatation and consequently MR. Regarding treatment, positive airway pressure devices used to ameliorate symptoms in SDB also seem to result in a reduction of MR severity, MR jet fraction and an improvement of left ventricular ejection fraction. However, surgical and transcatheter interventions for MR, and especially transcatheter edge to edge mitral valve repair (TEER), seem to also have a positive effect on SDB, by reducing OSA and CSA-related severity indexes and improving symptom control. The purpose of this review is to provide a comprehensive analysis of the common pathophysiology between SDB and MR, as well as to discuss the available evidence regarding the effect of SDB treatment on MR and the effect of mitral valve surgery or transcatheter repair on both OSA and CSA.

Therapeutic inertia in rhythm control strategies in hospitalized patients with fibrillation: Insights from Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

BACKGROUND: Current guidelines recommend a rhythm control strategy in patients with symptomatic atrial fibrillation (AF) while catheter ablation has been shown to be a safer and more efficacious approach than antiarrhythmic medications. METHODS: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. In this sub-study, we included 276 cases who had a history of AF, particularly on the rhythm strategy, and catheter ablation procedures had been performed before the index admission. RESULTS: Among 276 AF patients (mean age: 76.4 ±â€¯11.5 years, 58 % male), 60.9 % (N = 168) had persistent AF and 39.1 % (N = 108) had paroxysmal AF. Heart failure was the main cause of admission in 54.3 % (N = 145) of the patients, while 14.1 % (N = 39) were admitted due to paroxysmal AF, 7.3 % (N = 20) due to bradyarrhythmic reasons, and 6.5 % (N = 18) suffered from acute coronary syndrome. Most importantly, heart failure with reduced ejection fraction was present in 76 (27 %) patients. Only 10 patients out of the total (3 %, mean age 59.7 years) had undergone AF ablation while electrical cardioversion had been attempted in 37 (13.4 %) patients. Interestingly, in this AF population with heart failure, 3.6 % (N = 10) had a defibrillator implanted (4 single-chamber), and only 1.5 % (N = 4) had a cardiac resynchronization therapy defibrillator (CRT-D). CONCLUSION: High prevalence of persistent AF was detected in hospitalized patients, with heart failure being the leading cause of admission and main co-morbidity. Rhythm control strategies are notably underused, along with CRT-D implantation in patients with AF and heart failure.

Management of Patients With Unexplained Syncope: Derivation and Validation of a Simplified 2-Step Diagnostic Approach.

BACKGROUND: The aim of this study was to develop a structured 2-step approach, based on noninvasive diagnostic criteria, that led to an electrophysiology study in patients with unexplained syncope. METHODS AND RESULTS: Two independent cohorts were used: the derivation cohort with 665 patients based on electronic health record data to develop our 2-step diagnostic approach, and the validation cohort based on 160 prospectively screened patients, presenting with unexplained syncope episodes. Noninvasive electrocardiographic and imaging markers and an electrophysiology study-based invasive assessment were combined. A positive diagnostic approach according to our study's prespecified criteria resulted in a decision to proceed with a permanent pacemaker/implantable cardioverter-defibrillator. The primary end point was the time until the event of recurrent syncope (syncope-free survival). Number needed to treat was calculated for patients with a positive diagnostic approach. The number of patients with unexplained syncope and borderline sinus bradycardia needed to treat was 5, and the number of patients with unexplained syncope and bundle branch block needed to treat was 3 over a mean follow-up of ≈4 years. After the structured 2-step approach, the primary outcome occurred in 14 of 82 (17.1%) with a pacemaker/implantable cardioverter-defibrillator and 19 of 57 (33%) with a negative approach, with a mean follow-up of ≈2.5 years (29.29±12.58 months, P=0.03). CONCLUSIONS: The low number needed to treat in the derivation cohort and the low percentage of syncope recurrence in the validation cohort supports the proposed 2-step electrophysiology-inclusive algorithm as a potentially low-cost, 1-day, structured tool for these patients.

Anticoagulation Status and Left Atrial Appendage Occlusion Indications in Hospitalized Cardiology Patients with Atrial Fibrillation: A Hellenic Cardiorenal Morbidity Snapshot (HECMOS) Sub-Study.

Background and Objectives: The proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess anticoagulation status and LAAC indications in patients with AF from the HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: The HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on 3 March 2022 in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves or moderate-to-severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6 ± 11.7, 148 males) were included in our analysis. Most of them (n = 159; 62%) suffered from persistent AF. The mean CHA2DS2-VASc score was 4.28 ± 1.7, while the mean HAS-BLED score was 1.47 ± 0.9. Three out of three patients with a a CHA2DS2-VASc score of 0 or 1 (female) were inappropriately anticoagulated. Sixteen out of eighteen patients with a CHA2DS2-VASc score 1 or 2 (if female) received anticoagulants. Thirty-one out of two hundred thirty-five patients with a CHA2DS2-VASc score > 1 or 2 (if female) were inappropriately not anticoagulated. Relative indications for LAAC were present in 68 patients with NVAF (63 had only one risk factor and 5 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had an eGFR value < 15 mL/min/1.73 m2 for a total of 73 risk factors. Moreover, 33 had a HAS-BLED score ≥ 3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high-thromboembolic-risk population of cardiology patients who were mainly treated using NOACs. One out of four AF patients should be screened for LAAC.

Electrocardiographic Characteristics, Identification, and Management of Frequent Premature Ventricular Contractions.

Premature ventricular complexes (PVCs) are frequently encountered in clinical practice. The association of PVCs with adverse cardiovascular outcomes is well established in the context of structural heart disease, yet not so much in the absence of structural heart disease. However, cardiac magnetic resonance (CMR) seems to contribute prognostically in the latter subgroup. PVC-induced myocardial dysfunction refers to the impairment of ventricular function due to PVCs and is mostly associated with a PVC burden > 10%. Surface 12-lead ECG has long been used to localize the anatomic site of origin and multiple algorithms have been developed to differentiate between right ventricular and left ventricular outflow tract (RVOT and LVOT, respectively) origin. Novel algorithms include alternative ECG lead configurations and, lately, sophisticated artificial intelligence methods have been utilized to determine the origins of outflow tract arrhythmias. The decision to therapeutically address PVCs should be made upon the presence of symptoms or the development of PVC-induced myocardial dysfunction. Therapeutic modalities include pharmacological therapy (I-C antiarrhythmic drugs and beta blockers), as well as catheter ablation, which has demonstrated superior efficacy and safety.

Total Atrial Conduction Time as a Predictor of Atrial Fibrillation Recurrence: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to evaluate the predictive value of total atrial conduction time (TACT) assessed by tissue Doppler echocardiography (PA-TDI) in atrial fibrillation (AF) recurrence in patients following a rhythm-control strategy. A systematic approach following Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines was applied in electronic databases (Pubmed, Cochrane Library, and Web of Science), supplemented by scanning through studies' references. TACT was compared using a random-effects model and presented as a difference in means (MD). The primary endpoint was AF recurrence. Seven publications were included in this systematic review. The mean age of the patients ranged from 55 years to 72 years. Prolonged TACT was associated with AF recurrence [MD, 23.12 msec; 95% confidence interval (CI), 11.54-34.71; I2 = 95%]. Subgroup analysis showed that prolonged TACT was strongly associated with AF recurrence in persistent AF cohorts undergoing electrical cardioversion (MD, 26.56; 95% CI, 15.51-37.6; I2 = 86%), while in patients with paroxysmal AF (PAF) undergoing catheter ablation, the results were not statistically significant (MD, 11.48; 95% CI, -1.19 to 24.14; I2 = 90%). The summary area under the curve (sAUC) using a random-effects model was 0.89 (95% CI, 0.80-0.99). TACT is a valuable echocardiographic parameter that can predict AF recurrence in patients following a rhythm-control strategy. Protocol registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353018.

Effects of dietary interventions on cardiovascular outcomes: a network meta-analysis.

CONTEXT: Next to a large body of epidemiological observational studies showing that the Mediterranean diet (MD) is an important lifestyle determinant of cardiovascular risk, there is less relevant evidence from well-conducted randomized controlled trials (RCTs) with hard cardiovascular outcomes. OBJECTIVE: The objective of the study was to identify the most effective dietary intervention for reducing cardiovascular morbidity and mortality. DATA SOURCES: A systematic approach following PRISMA network meta-analyses reporting guidelines was applied to a search of electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Embase) without language restrictions, supplemented by scanning through bibliographies of studies and meetings' abstract material. Inclusion criteria were RCTs conducted in an adult population, investigating the effects of different type of diets or dietary patterns on all-cause mortality and cardiovascular outcomes of interest. DATA EXTRACTION: Data extraction for each study was conducted by 2 independent reviewers. DATA ANALYSIS: A frequentist network meta-analysis using a random-effects model was conducted. Death from any cardiovascular cause was defined as the primary outcome. A total of 17 trials incorporating 83 280 participants were included in the systematic review. Twelve articles (n = 80 550 participants) contributed to the network meta-analysis for the primary outcome. When compared with the control diet, only the MD showed a reduction in cardiovascular deaths (risk ratio = 0.59; 95% confidence interval, 0.42-0.82). Additionally, MD was the sole dietary strategy that decreased the risk of major cardiovascular events, myocardial infarction, angina, and all-cause mortality. CONCLUSIONS: MD may play a protective role against cardiovascular disease and death for primary and also secondary prevention. SYSTEMATIC REVIEW REGISTRATION: Center for Open Science, https://doi.org/10.17605/OSF.IO/5KX83.

Rationale and Design of a Randomized Controlled Clinical Trial on the Safety and Efficacy of Flecainide versus Amiodarone in the Cardioversion of Atrial Fibrillation at the Emergency Department in Patients with Coronary Artery Disease (FLECA-ED).

Pharmacologic cardioversion is a well-established alternative to electric cardioversion for hemodynamically stable patients, as it skips the risks associated with anesthesia. A recent network meta-analysis identifies the most effective antiarrhythmics for pharmacologic cardioversion with flecainide exhibiting a more efficacious and safer profile towards faster cardioversion. Moreover, the meta-analysis of class Ic antiarrhythmics revealed an absence of adverse events when used for pharmacologic cardioversion of AF in the ED, including patients with structural heart disease. The primary goals of this clinical trial are to prove the superiority of flecainide over amiodarone in the successful cardioversion of paroxysmal atrial fibrillation in the Emergency Department and to prove that the safety of flecainide is non-inferior to amiodarone in patients with coronary artery disease without residual ischemia, and an ejection fraction over 35%. The secondary goals of this study are to prove the superiority of flecainide over amiodarone in the reduction in hospitalizations from the Emergency Department due to atrial fibrillation in the time taken to achieve cardioversion, and in the reduction in the need to conduct electrical cardioversion.

Management of Patients With Unexplained Syncope and Bundle Branch Block: Predictive Factors of Recurrent Syncope.

Syncope in patients with bundle branch block (BBB) is often due to advanced atrioventricular (AV) block. The objective of the present "real-world" study was to evaluate the optimal management in patients with unexplained syncope and BBB and to identify factors that predict the recurrence of syncope. This is a single-center observational prospective registry of 131 consecutive patients undergoing invasive electrophysiology study (EPS) for recurrent unexplained presyncope or syncope attacks and BBB. When the EPS-derived diagnosis was reached, a decision to proceed with a permanent pacemaker was offered to the patient. An implantable loop recorder was inserted in the rest of the population. A total of 131 consecutive patients with unexplained syncope and BBB (67.2% male; age 63.7 ± 16.5 years) underwent EPS during the study period. The distribution of conduction disturbance patterns was as follows: isolated left bundle branch block (LBBB): 23.7%; LBBB with first AV block: 8.4%; isolated right bundle branch block (RBBB): 10.7%; RBBB with first AV block: 8.4%; isolated left anterior/posterior fascicular block: 13%; left anterior/posterior fascicular block with first AV block: 5.3%; isolated bifascicular block: 16.8%; and bifascicular block with first AV block: 13.7%. In the multivariate analysis, the only predictors of recurrent syncope were bifascicular block (hazard ratio (HR): 4.16, 95% confidence interval (CI): 1.29, 13.41, P: 0.017) and HV interval ≥ 60 msec (HR: 3.58, 95% CI: 1.12, 11.46, P: 0.032). An EPS-based strategy identifies a subset of patients who will benefit from permanent pacing. HV interval ≥ 60 msec and the presence of a bifascicular block were strongly related to syncope recurrence.

Effectiveness and safety of a time to isolation strategy of cryoballoon ablation of atrial fibrillation: A systematic review and meta-analysis.

AIM: We conducted a systematic review and meta-analysis of randomized and observational studies with a control group to evaluate the effectiveness and safety of a time to isolation (TTI)-based strategy of cryoballoon ablation (CBA) in the treatment of atrial fibrillation (AF). METHODS: Three electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Embase) without language restrictions were searched. The intervention assessed was a TTI-based strategy of CBA in the treatment of AF. TTI was defined as the time from the start of freezing to the last recorded pulmonary veins' potential. The comparison of interest was intended conventional protocol of CBA. The primary endpoint was freedom from atrial arrhythmia. RESULTS: Nine studies were deemed eligible (N = 2289 patients). Eight studies reported freedom from atrial arrhythmia and pooled results showed a marginally similar success rate between the two protocols (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 0.98-1.56). A prespecified subgroup analysis verified that a high dose TTI strategy (with >120 s duration of cryotherapy post-TTI) compared to the conventional protocol could significantly increase the patients without atrial arrhythmia during follow-up (OR: 1.39; 95% CI: 1.05-1.83). TTI strategy could also significantly decrease total procedure time (SMD: -26.24 min; 95% CI: -36.90 to -15.57) and phrenic nerve palsy incidence (OR: 0.49; 95% CI: 0.29-0.84). CONCLUSION: Moderate confidence evidence suggests that an individualized CBA dosing strategy based on TTI and extended (>2 min post-TTI) duration of CBA is accompanied by fewer recurrences post-AF ablation.

Reappraising the role of class Ic antiarrhythmics in atrial fibrillation.

PURPOSE: The objective of the present systematic review was to compare the effectiveness and safety of class Ic agents for cardioversion of paroxysmal atrial fibrillation (AF), in patients with and without structural heart disease (SHD). METHODS: We focused on RCTs enrolling at least 50 adult patients with electrocardiogram-documented paroxysmal AF that compared either two pharmacological class Ic cardioversion agents (flecainide, propafenone), regardless of study design (parallel or crossover). We searched MEDLINE and the Cochrane Central Register of Controlled Trials. Initial search was performed from inception to 15 July 2021 with no language restrictions. RESULTS: Intravenous flecainide is the most effective option for pharmacologic cardioversion of AF since only 2 patients need to be treated in order to cardiovert one more within 4 h. Most importantly, class Ic agents appear to be safe in the context of pharmacologic cardioversion of AF irrespective of the presence of SHD, pointing towards a possible reappraisal of the role in this setting. CONCLUSION: We suggest that class Ic agents (with flecainide appearing to be more effective) should be used for pharmacologic cardioversion in stable AF patients presenting in emergency department with unknown medical history, after excluding severe cardiac disease through a bedside examination. REGISTRATION NUMBER (DOI): Available in https://osf.io/apwt7/ , https://doi.org/10.17605/OSF.IO/APWT7.

Autonomic Neuromodulation for Atrial Fibrillation Following Cardiac Surgery: JACC Review Topic of the Week.

Autonomic neuromodulation therapies (ANMTs) (ie, ganglionated plexus ablation, epicardial injections for temporary neurotoxicity, low-level vagus nerve stimulation [LL-VNS], stellate ganglion block, baroreceptor stimulation, spinal cord stimulation, and renal nerve denervation) constitute an emerging therapeutic approach for arrhythmias. Very little is known about ANMTs' preventive potential for postoperative atrial fibrillation (POAF) after cardiac surgery. The purpose of this review is to summarize and critically appraise the currently available evidence. Herein, the authors conducted a systematic review of 922 articles that yielded 7 randomized controlled trials. In the meta-analysis, ANMTs reduced POAF incidence (OR: 0.37; 95% CI: 0.25 to 0.55) and burden (mean difference [MD]: -3.51 hours; 95% CI: -6.64 to -0.38 hours), length of stay (MD: -0.82 days; 95% CI: -1.59 to -0.04 days), and interleukin-6 (MD: -79.92 pg/mL; 95% CI: -151.12 to -8.33 pg/mL), mainly attributed to LL-VNS and epicardial injections. Moving forward, these findings establish a base for future larger and comparative trials with ANMTs, to optimize and expand their use.

Permanent pacemaker implantation in unexplained syncope patients with electrophysiology study-proven atrioventricular node disease.

OBJECTIVE: Syncope, whose cause is unknown after an initial assessment, has an uncertain prognosis. It is critical to identify patients at the highest risk who may require a pacemaker and to identify the cause of recurrent syncope to prescribe proper therapy. The aim of this study was to evaluate the effect of permanent pacing on the incidence of syncope in patients with unexplained syncope and electrophysiology study (EPS)-proven atrioventricular (AV) node disease. METHODS: This was an observational study based on a prospective registry of 236 consecutive patients (60.20 ± 18.66 years, 63.1% male, 60.04 ± 9.50 bpm) presenting with recurrent unexplained syncope attacks admitted to our hospital for invasive EPS. The decision to implant a permanent pacemaker was made in all cases by the attending physicians according to the results of the EPS. A total of 135 patients received the antibradycardia pacemaker (ABP), while 101 patients were declined. RESULTS: The mean of reported syncope episodes was 1.97 ± 1.10 (or presyncope 2.17 ± 1.50) before they were referred for a combined EP-guided diagnostic and therapeutic approach. Over a mean follow-up of approximately 4 years (49.19 ± 29.58 months), the primary outcome event (syncope) occurred in 31 of 236 patients (13.1%), and 6 of 135 (4.4%) patients in the ABP group as compared to 25 of 101 (24.8%) in the no pacemaker group (p < 0.001). CONCLUSION: Among patients with a history of unexplained syncope, a set of positivity criteria for the presence of EPS-defined AV node disease identifies a subset of patients who will benefit from permanent pacing.

Atrial High-Rate Episodes in Patients with Devices Without a History of Atrial Fibrillation: a Systematic Review and Meta-analysis.

PURPOSE: Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF. METHODS: We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs. RESULTS: We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87-6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19-3.05). AHREs were not associated with a statistically significant increased mortality risk. CONCLUSION: The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke. REGISTRATION NUMBER (DOI): Available in https://doi.org/10.17605/OSF.IO/ZRF6M .