Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 appraisals
European journal of clinical pharmacology
Impact of carvedilol versus metoprolol on ventricular arrhythmia burden and ICD therapies: a systematic review and meta-analysis
BACKGROUND: Ventricular arrhythmias (VA) are major causes of morbidity and mortality in patients with cardiovascular disease. Implantable cardioverter-defibrillators (ICDs) are commonly used to prevent sudden cardiac death. However, patients with ICDs frequently experience recurrent arrhythmias and inappropriate shocks, which impact quality of life. Beta-blockers, specifically carvedilol and metoprolol, are commonly prescribed in this context. This meta-analysis aims to compare the impact of both medications in this patient population. METHODS: Comprehensive literature search was conducted to identify relevant studies comparing carvedilol to metoprolol in patients with VA or ICDs. Study outcomes included all-cause mortality, recurrent VA, and inappropriate ICD shocks. Effect estimates are presented as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Five independent study populations, reported across six publications, including 7,777 patients (5,138 on carvedilol, 2,639 on metoprolol) were analyzed. Carvedilol was associated with a significantly lower risk of inappropriate ICD shocks (HR = 0.66, 95% CI: 0.48-0.90, P = 0.009) and inappropriate anti-tachycardia pacing (HR = 0.67, 95% CI: 0.49-0.91, P = 0.01) compared with metoprolol. There were no significant differences between the two beta-blockers in recurrent ventricular tachyarrhythmias or all-cause mortality. CONCLUSION: Carvedilol may provide additional benefit over metoprolol in reducing inappropriate ICD therapies and anti-tachycardia pacing, while no significant differences were found in recurrent ventricular arrhythmias or all-cause mortality. These findings support consideration of carvedilol in patients with ICDs, but further research is warranted to guide optimal beta-blocker selection.
15 July 2026
Read appraisal →Open heart
Predictors of high-grade atrioventricular block recovery in Takotsubo cardiomyopathy: a systematic review of case reports
BACKGROUND: Atrioventricular block (AVB) in Takotsubo cardiomyopathy (TCM) is a rarely reported complication. Due to its low incidence and lack of randomised trials, there remain significant gaps in the evidence regarding its underlying mechanisms, the probability of conduction recovery and the optimal timing for permanent pacemaker implantation. METHODS: A systematic review was conducted on published case reports on TCM associated with high-grade AVB, diagnosed simultaneously or within the same hospital admission. Cases with low-grade AVB, sole sinus node disease or TCM induced by pacemaker implantation were excluded. RESULTS: A total of 50 cases were included in the final analysis; stratified into two groups based on AVB recovery. Fifteen patients (30%) developed complete AVB recovery. Compared with persistent AVB, those who experienced recovery were younger (median (IQR): 66 (61-73) vs 77 (65-82), p=0.02), more frequently reported identifiable emotional or physical stressors (93% vs 49%, p=0.004) and demonstrated earlier recovery of left ventricular ejection fraction (LVEF) within 1 week (60% vs 24%, p=0.02). No significant differences were observed in terms of comorbidities (hypertension in 27% vs 47%, p=0.22), presenting symptoms (chest pain in 40% vs 14%, syncope or presyncope in 27% vs 46%, p=0.22), ST elevation (27% vs 14%, p=0.28) or regional wall motion abnormalities (apical akinesia in 47% vs 46%, p=0.93). On multivariate analysis, the presence of an identifiable stressor was an independent predictor of AVB recovery (HR 8.27; 95% CI 1.07 to 63.73, p=0.04). CONCLUSION: In patients with TCM and high-grade AVB, the absence of a clear stressor highlights the possibility of baseline conduction disorder, with a higher risk of persistent AVB. Earlier LVEF recovery and younger age may help to predict AVB recovery and guide patient selection for PPM implantation. PROSPERO REGISTRATION NUMBER: CRD420251173831.
24 May 2026
Read appraisal →Journal of medical economics
A systematic review of acute and long-term outcomes in patients with non-transvenous implantable cardioverter-defibrillators
BACKGROUND: Non-transvenous implantable cardioverter-defibrillator (ICD) systems have been developed to address limitations of transvenous ICDs. This systematic literature review aimed to summarize periprocedural and long-term outcomes of non-transvenous ICD systems in adult patients with guideline-based indications for ICD therapy. METHODS: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420261327618). Eligible studies enrolled adults (≥18 years) receiving a non-transvenous ICD for primary or secondary prevention. Outcomes included periprocedural and long-term endpoints and were summarized descriptively. The Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) checklist for case series were used to assess risk of bias. RESULTS: Twenty-five publications representing 18 unique studies and 4,633 patients were included. Most studies were single-arm (n = 13), while 2 were randomized controlled trials and 3 were nonrandomized comparative studies. Procedural success ranged from 81%-100%, with rates ≥94% of patients in all but one early-phase study; defibrillation threshold testing success ranged from 89%-100% (≥96% in studies with n ≥ 100). Periprocedural complications were reported in 0%-5% of patients in most studies. Long-term complication rates ranged from 0%-8% at 0.5-1.5 years of follow-up and 1%-14% beyond 1.5 years. All-cause mortality ranged from 1%-5% within 6 months and increased to 16%-26% at 4-8 years. Clinical defibrillation success was consistently high (95%-100%). Incidence of inappropriate shock generally ranged from 7%-13% at 1 year and 2%-18% at later timepoints. Appropriate shock incidence ranged from 2% to 9% within 1 year and increased with longer follow-up. Risk of bias was predominantly moderate, with limited variation using NOS and greater discrimination observed with JBI. CONCLUSIONS: Non-transvenous ICD systems demonstrate favorable safety and effectiveness profiles, with high procedural and defibrillation success and acceptable complication and inappropriate shock rates across studies. Overall, the available evidence supports their use in appropriately selected adult patients with standard ICD indications. Non-transvenous implantable cardioverter-defibrillators (ICDs) are devices placed outside the blood vessels and heart, designed to treat life-threatening heart rhythm problems while avoiding complications related to transvenous ICDs.This review summarized results from 25 published studies including 4,600 patients to understand how safe and effective these devices are.Across studies, non-transvenous ICDs showed high implant procedure success, effective therapy delivery, and had generally low rates of short- and long-term complications.
23 May 2026
Read appraisal →JMIR mHealth and uHealth
A Deep Neural Network for Interpreting Wearable Electrocardiogram Data in Atrial Fibrillation: Prospective Observational Diagnostic Accuracy Study
BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFL) are common arrhythmias associated with the risk of ischemic stroke, which can be reduced with anticoagulation therapy. Thus, early diagnosis of AF and AFL is essential. However, diagnosis may be challenging due to the paroxysmal and asymptomatic nature of these arrhythmias. OBJECTIVE: Current diagnostic workflows involve time-consuming and resource-intensive manual review of noisy signals and prolonged recordings. We evaluated a mobile system that combines a wireless wearable single-lead chest strap electrocardiogram (ECG) and a novel deep neural network (DNN)-based artificial intelligence (AI) method for detecting AF/AFL episodes, AF/AFL burden, and rhythm change and estimated the delay in the detection of rhythm change from AF/AFL to sinus rhythm. We also assessed the rhythm classification performance. METHODS: A total of 116 patients with recent-onset AF or AFL undergoing cardioversion were monitored using a mobile single-lead chest strap ECG system. Simultaneously, a 3-lead Holter ECG served as the reference. The DNN-based AI analyzed the single-lead chest strap ECG data to detect AF/AFL, non-AF/AFLrhythm, and noninterpretable segments, as well as to estimate AF/AFL burden and detect rhythm change. Performance metrics included sensitivity, specificity, positive predictive value, negative predictive value, and intraclass correlation coefficient for AF and AFL burden estimation. RESULTS: The sensitivity and specificity for detecting AF/AFL were 91.9% (204.9/223.0 h) and 99.6% (242.4/243.5 h), respectively. The sensitivity for detecting AF was 96.2% (191.5/199.0 h), whereas it was 55.8% (13.4/24.0 h) for detecting AFL. The positive predictive value and negative predictive value for AF/AFL detection were 99.5% (204.9/206.0 h) and 93.1% (242.4/260.5 h), respectively. The intraclass correlation coefficient between the AF/AFL burden estimated by the DNN-based AI method and that derived from the physician-interpreted reference ECG was 0.96 (95% CI: 0.94-0.97; P<.001). Rhythm change detection occurred within 1 minute in most cases. CONCLUSIONS: The mobile single-lead chest strap ECG system powered by a DNN-based AI algorithm demonstrated strong performance in detecting AF, estimating AF burden, and recognizing rhythm change to sinus rhythm. This AI-driven approach enables automated and accurate rhythm analysis, supporting clinical decision-making. Further validation in real-world ambulatory settings is warranted.
25 Apr 2026
Read appraisal →Circulation
Memantine for Premature Atrial Contractions: A Phase 2 Randomized Clinical Trial
BACKGROUND: Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS: We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS: Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS: In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.
23 Apr 2026
Read appraisal →Journal of the American College of Cardiology
Pulsed Field Ablation vs Standard Radiofrequency Ablation for Typical Atrial Flutter: ADVANTAGE AF Trial Substudy
BACKGROUND: ADVANTAGE AF examined the safety and efficacy of pulsed field ablation (PFA) to treat persistent atrial fibrillation (AF). During AF ablation, typical atrial flutter (AFL) is commonly treated with cavotricuspid isthmus (CTI) ablation. OBJECTIVES: Adjunctive CTI ablation in ADVANTAGE AF was performed with radiofrequency ablation (RFA; phase 1) or bipolar linear PFA (phase 2). Here, we compared lesion characteristics, CTI ablation efficacy, and safety between the ablation modalities. METHODS: A preclinical study assessed lesion dimensions with a novel 2.0 kV bipolar linear PFA catheter. In ADVANTAGE AF, after AF ablation with a pentaspline PFA catheter, CTI ablation was performed: in phase 1 with irrigated RFA, and in phase 2 with the linear PFA catheter (Farapoint). Before PFA CTI ablation ,patients were treated with a vasopressor bolus followed by high-dose intravenous nitroglycerin. RESULTS: Preclinical assessment showed lesion depth increasing at higher field strength and plateauing after 2 applications. In ADVANTAGE AF, 50 and 141 patients received CTI ablation with RFA and PFA, respectively. Patient characteristics across the 2 cohorts were similar (RFA vs PFA). Acute CTI conduction block was similar between techniques (50 of 50 RFA [100%] vs 139 of 141 PFA [98.6%]; P = 1.00). PFA was associated with a shorter CTI ablation time (median: RFA 5 min [Q1-Q3: 4-8 min] vs 14 min [Q1-Q3: 9-19 min]; P = 0.001). RFA and PFA had similar safety event rates (RFA 2.0% vs PFA 2.1%; P = 0.96). With the use of nitroglycerin pretreatment, there was no clinical manifestation of coronary artery spasm with PFA. CONCLUSIONS: This subanalysis of ADVANTAGE AF extends the primary results by allowing comparison of bipolar linear PFA and RF ablation for CTI, integrating preclinical lesion modeling with clinical dosing, and establishing a standardized reliable coronary safety protocol. Although not randomized comparisons, these findings suggest that CTI ablation with a linear PFA catheter is associated with safety and efficacy similar to RF ablation and greater efficiency. (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation [ADVANTAGE AF; NCT05443594]).
16 Apr 2026
Read appraisal →Biomedical physics & engineering express
Differentiating long QT syndrome genotypes using electrocardiographic geometric parameterization and machine learning approaches
Long QT Syndrome (LQTS) is an inherited cardiac disorder characterized by dysfunctional cardiac ion channels, which result in prolonged QT intervals on electrocardiograms (ECGs). LQTS can lead to severe clinical manifestations, including syncope, ventricular arrhythmias, and sudden cardiac death. Effective genotype-specific management strategies are essential to mitigate the risk of life-threatening arrhythmias. This study aims to achieve automatic discrimination among the LQT1, LQT2, and LQT3 genotypes to enable targeted treatment and prevention strategies. Utilizing ECG data from the Telemetric and Holter ECG Warehouse's LQTS database, our methodology involves an automated extraction process of short ECG signals, geometric parameterization techniques, and classification using a two-stage cascade of binary support vector machine classifiers. The input features for the classifiers are derived from Lead I ECG signals sampled at 200 Hz, highlighting the potential application in developing single-lead ECG monitoring devices and applications, such as widely used smartwatches, for which short recording duration, low sampling frequency, and arm-to-arm lead measurements are fundamental prerequisites for practical use. The proposed classifier achieved 71% weighted accuracy on out-of-sample data (LQT1: 65% recall, 58% precision; LQT2: 79% recall, 82% precision; and LQT3: 71% recall, 77% precision). Our findings demonstrate the feasibility of noninvasive genotype differentiation for LQTS based on the morphological analysis of ECG signals, providing an advancement in the field of personalized cardiology and the development of portable diagnostic tools.
11 Apr 2026
Read appraisal →ACS applied materials & interfaces
NeuroTex: Functionalized Hybrid Polymer-Metal Textile for Soft, Robust, and Dry Auricular Neural Interfaces
Wearable bioelectronics would benefit from dry, easy-to-apply electrodes for sensing physiological signals. Bioelectronic interfaces must maintain high conductivity, low electrode-skin impedance, and reliable coupling between the electrode and skin under sweat, motion, and prolonged use. Metallic textiles offer good conductivity and stable connections but are hydrophobic, prone to cracking and oxidation, and dependent on conductive gels to achieve the low impedance required for low-amplitude electrophysiological signals. Here, we introduce NeuroTex, a commercially available silver nanowire textile that is PEDOT:PSS-functionalized to improve the electrode-skin-electronics interface. The PEDOT:PSS coating reduced the area-normalized resistance of the textile by almost 50%, suppressed silver oxidation in phosphate-buffered saline, and lowered the contact impedance by more than 85%. Mechanical evaluations under torsion, stretching, bending, and low-force fatigue confirmed the preserved fiber integrity and intact electronic connectivity. Furthermore, the soft and hydrophilic properties of the coating enhanced the conformal skin interfacing. Integrated into an in-ear monitoring platform, NeuroTex enabled multimodal biosignal recordings of in-ear electroencephalography (ieEEG), electro-oculography (ieEOG), electromyography (ieEMG), and electrocardiography (ieECG). Reliable acquisition of the technically demanding ieEEG signal was achieved, demonstrating alpha-modulation responses comparable to those of gel-based electrodes. ieEEG recordings recorded over several hours captured distinct sleep patterns to further confirm stable performance during natural sleep. These results establish NeuroTex as a gel-free, mechanically resilient, and electrochemically stable interface suitable for wearable physiological monitoring.
10 Apr 2026
Read appraisal →Journal of the American Heart Association
Patient Care Pathways and Outcomes Following Newly Diagnosed Atrial Fibrillation
BACKGROUND: Care pathways for patients with atrial fibrillation (AF) are poorly understood and may influence the likelihood of guideline concordant oral anticoagulation or antiarrhythmic drug therapy and associated outcomes. METHODS: Adult patients in the Optum Clinformatics Database (2015-2023) with incident AF were identified. Care pathways, by treating clinician specialty (primary care, cardiology, electrophysiology) during each AF-related visit in the 1 year post diagnosis were examined. Cox regression models were used to assess associations between an electrophysiologist visit and AF-related treatments including antiarrhythmic drug therapy and oral anticoagulation and outcomes including AF-related hospitalizations, heart failure hospitalizations, and stroke. RESULTS: Of the 37 370 patients included, 7700 (20.6%) had a care pathway including an electrophysiologist visit. Older patients (70-79 and 80+ versus 18-49 years: hazard ratio [HR], 0.71 [95% CI, 0.64-0.78] and HR, 0.57 [95% CI, 0.51-0.63], respectively) and those with a higher CHA2DS2-VASc score (2-3 and ≥4 versus 0-1: HR, 0.79 [95% CI, 0.74-0.85] and HR, 0.76 [95% CI, 0.68-0.84], respectively) were less likely to have an electrophysiologist visit. Electrophysiologist visits were associated with a significant increase in rates of treatment with antiarrhythmic drug and oral anticoagulation. Patients aged ≥80 years with an electrophysiologist visit had significantly lower risks of stroke compared with those without an electrophysiologist visit (HR, 0.63 [95% CI, 0.42-0.95]). CONCLUSIONS: Certain demographic groups including older patients had lesser likelihood of electrophysiologist consultation, but guideline concordant care was more likely associated with electrophysiology care pathways. Electrophysiology care pathways were associated with improved outcomes especially among the groups with greatest stroke risk.
8 Apr 2026
Read appraisal →The New England journal of medicine
Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation
BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).
4 Apr 2026
Read appraisal →Heart rhythm
External validation of an explainable electrocardiogram-only deep learning algorithm for the prediction of response after cardiac resynchronization therapy
BACKGROUND: Cardiac resynchronization therapy (CRT) can improve clinical outcomes in patients with dyssynchronous heart failure, but many patients selected according to the current guidelines do not respond. OBJECTIVE: This study aimed to externally validate an explainable deep learning algorithm (the FactorECG algorithm) for predicting response after biventricular pacing. METHODS: We previously trained a deep learning algorithm on >1 million electrocardiogram (ECG) median beats to learn the underlying generative factors of the ECG and applied it to 1306 patients with CRT from the Netherlands. Using the extracted 21 explainable factors, a model predicting the risk of volumetric nonresponse and poor clinical outcomes was developed. In the present analysis, this model was externally validated in a cohort of 161 patients with CRT from the University of Virginia for volumetric nonresponse only. Subsequently, the added value of clinical and cardiac magnetic resonance imaging-derived predictors was investigated. RESULTS: The original model significantly outperformed American Heart Association criteria for left bundle branch block for the prediction of nonresponse {C-statistic 0.67 (95% confidence interval [CI] 0.59-0.76) vs 0.51 (95% CI 0.41-0.60), respectively}. A refitted FactorECG-based model performed similarly to a model also integrating indices of mechanical dyssynchrony (C-statistic 0.74 [95% CI 0.66-0.82] vs 0.70 [95% CI 0.62-0.77], respectively). A combination of both models improved response prediction (C-statistic 0.79 [95% CI 0.71-0.85]). CONCLUSION: In this external validation study, an explainable ECG-only algorithm for the prediction of nonresponse after CRT device implantation generalized well to a lower-risk population from a different hospital. Adding indices of mechanical dyssynchrony and right ventricular function might be of additional value when evaluating volumetric response.
4 Apr 2026
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