Noninvasive risk assessment and prediction of cardiac outcomes in patients with congestive heart failure or myocardial infarction.

BACKGROUND: Heart rate turbulence (HRT) and T-wave alternans (TWA), recognized as promising noninvasive markers for ventricular tachyarrhythmias and cardiac death, have been studied predominantly in Western populations, specifically in patients with myocardial infarction (MI) or heart failure (HF) with reduced ejection fraction (EF). OBJECTIVE: The purpose of this study was to investigate the clinical implications of HRT and TWA in predicting adverse cardiac events, including cardiac death, ventricular tachyarrhythmia, and heart failure-related hospitalization (HFH). METHODS: The K-REDEFINE study, a prospective, observational, multicenter analysis of 26 tertiary hospitals in South Korea, investigated the prognostic implications of Holter-based variables including HRT and TWA in 1116 patients with acute MI or HF (age 60.8 ± 2.9 years; 76.3% male). All participants underwent 24-hour Holter recording within 6.8 ± 16.5 days after hospitalization. The primary composite outcome included cardiac death, ventricular tachyarrhythmias, and HFH. RESULTS: During 4.3 ± 1.2 years of follow-up, impaired HRT demonstrated the most powerful predictive value for the composite (adjusted hazard ratio [aHR] 3.41, 95% confidence interval [CI] 2.27-5.13) or individual events: cardiac death (aHR 4.08, 95% CI 2.17-7.70), ventricular tachyarrhythmia (aHR 3.72, 95% CI 1.29-10.77), and HFH (aHR 4.32, 95% CI 2.25-8.28). The predictive power of abnormal HRT remained consistently significant across subgroups of MI and HF, or across varying degrees of EF. When combined with reduced EF (<50%), the predictive power was further enhanced. However, abnormal TWA was significantly associated only with the composite outcome (aHR 1.51, 95% CI 1.06-2.16). CONCLUSION: The K-REDEFINE study identified abnormal HRT, mostly assessed within 1 month after hospitalization, as a significant predictor not only for cardiac death and ventricular tachyarrhythmia but also for HFH.

Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease.

BACKGROUND: Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. METHODS: We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding. RESULTS: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).

Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

Long-term clinical impact of early recurrence of atrial tachyarrhythmia after cryoballoon ablation in patients with atrial fibrillation.

INTRODUCTION: The impact of early recurrence of atrial tachyarrhythmia (ERAT) within the 90-day blanking period on long-term outcomes in atrial fibrillation (AF) patients undergoing cryoballoon ablation (CBA) is controversial. This study aimed to assess the relationship between ERAT and late recurrence of atrial tachyarrhythmia (LRAT) post-CBA. METHODS: Utilizing data from a multicenter registry in Korea (May 2018 to June 2022), we analyzed the presence and timing of ERAT (<30, 30-60, and 60-90 days) and its association with LRAT risk after CBA. LRAT was defined as any recurrence of AF, atrial flutter, or atrial tachycardia lasting more than 30 s beyond the 90 days. RESULTS: Out of 2636 patients, 745 (28.2%) experienced ERAT post-CBA. Over an average follow-up period of 21.2 ± 10.3 months, LRAT was observed in 874 (33.1%) patients. Patients with ERAT had significantly lower 1-year LRAT freedom compared to those without ERAT (42.6% vs. 85.5%, p < .001). Multivariate analysis identified ERAT as a potential predictor of LRAT, with a hazard ratio (HR) of 3.98 (95% confidence interval [CI], 3.47-4.57). Significant associations were noted across all examined time frames (HR, 3.84; 95% CI, 3.32-4.45 in <30 days, HR, 5.53; 95% CI, 4.13-7.42 in 30-60 days, and HR, 4.29; 95% CI, 3.12-5.89 in 60-90 days). This finding was consistently observed across all types of AF. CONCLUSION: ERAT during the 90-day blanking period strongly predicts LRAT in AF patients undergoing CBA, indicating a need to reconsider the clinical significance of this period.

Comparison between catheter ablation versus permanent pacemaker implantation as an initial treatment for tachycardia-bradycardia syndrome patients: a prospective, randomized trial.

BACKGROUND: Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for the tachycardia-bradycardia syndrome (TBS) has not been evaluated adequately. We tried to compare the efficacy and safety outcomes of CA and PM implantation as an initial treatment option for TBS in paroxysmal atrial fibrillation (AF) patients. METHODS: Sixty-eight patients with paroxysmal AF and TBS (mean 63.7 years, 63.2% male) were randomized, and received CA (n = 35) or PM (n = 33) as initial treatments. The primary outcomes were unexpected emergency room visits or hospitalizations attributed to cardiovascular causes. RESULTS: In the intention-to-treatment analysis, the rates of primary outcomes were not significantly different between the two groups at the 2-year follow-up (19.8% vs. 25.9%; hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.25-2.20, P = 0.584), irrespective of whether the results were adjusted for age (HR 1.12, 95% CI 0.34-3.64, P = 0.852). The 2-year rate of recurrent AF was significantly lower in the CA group compared to the PM group (33.9% vs. 56.8%, P = 0.038). Four patients (11.4%) in the CA group finally received PMs after CA owing to recurrent syncope episodes. The rate of major or minor procedure related complications was not significantly different between the two groups. CONCLUSION: CA had a similar efficacy and safety profile with that of PM and a higher sinus rhythm maintenance rate. CA could be considered as a preferable initial treatment option over PM implantation in patients with paroxysmal AF and TBS. TRIAL REGISTRATION: KCT0000155.

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation under anticoagulation therapy.

BACKGROUND: Left atrial thrombus (LAT) formation is associated with thromboembolic events. OBJECTIVE: To investigate the incidence and associated factors of LAT in patients with atrial fibrillation (AF) who had been receiving anticoagulation therapy for more than 4 weeks, and to develop a prediction model using clinical and echocardiographic features. METHODS: Medical records of 1,122 patients with AF (mean age, 59.4 ± 11.0 years, 58.3% male) who were on anticoagulation more than 4 weeks and underwent transesophageal echocardiography (TEE) were evaluated. The main outcome was the presence of LAT on TEE. RESULTS: Warfarin and non-vitamin K oral anticoagulants were used in 74.4% and 25.6% of the patients at the time of examination, respectively. LAT was present in 60 patients (5.3%). Presence of LAT on TEE was associated with age ≥ 75 years (odds ratio [OR] 2.13 [95% confidence interval, 0.94-4.58]), persistent/permanent AF (OR 2.61 [1.42-4.93]), CHA2DS2-VASc score ≥ 3 points (OR 1.91 [1.05-3.48]), left ventricular ejection fraction < 40% (OR 2.35 [1.07-4.81]), and severe left atrial enlargement (OR 3.52 [1.89-6.79]). The presence of moderate-to-severe mitral regurgitation was associated with a lower risk of LAT (OR 0.13 [0.04-0.34]). A scoring system composed of the aforementioned predictors showed excellent discrimination performance (area under the curve 0.791 [95% CI, 0.727-0.854]). CONCLUSIONS: LAT was present in a considerable number of patients who were already receiving anticoagulation therapy. A prediction model that combines clinical and echocardiographic predictors could be useful in distinguishing patients who require imaging evaluations before left atrial intervention.

Reduction of moderate to severe tricuspid regurgitation after catheter ablation for atrial fibrillation.

OBJECTIVE: Tricuspid regurgitation (TR) is a progressive disease with high mortality and limited medical treatment options, and its association with atrial fibrillation (AF) has been documented. This study aimed to investigate whether successful rhythm control through catheter ablation for AF could reduce TR severity. METHODS: A total of 106 patients with drug-refractory AF with moderate to severe secondary TR who underwent AF ablation were screened from a single-centre ablation registry. Echocardiographic parameter changes (pre-procedure vs 1 day/1 year post-procedure) were analysed. Holter monitoring was performed at 3/6/12 months to assess AF recurrence. The primary outcome was at least one grade TR reduction with its main determinants evaluated. RESULTS: After excluding 36 patients (prior tricuspid valve surgery, intracardiac devices or insufficient data), 70 patients (aged 63.8±9.7 years, 50% female) were analysed. Of these, 17 (24.3%) had severe TR, 55 (78.6%) persistent AF and all restored sinus rhythm with catheter ablation. The primary outcome was achieved in 53 (75.7%) at 1-year assessment (73.6% of moderate and 82.4% of severe TR). There were significant decreases of vena contracta (6.1→3.2 mm) and tricuspid annular diameter (37.3→32.6 mm) at 1 year. Although 25 patients experienced AF recurrence within 1 year, 56 (80%) patients finally maintained sinus rhythm with medical treatment (87% in patients with TR reduction and 59% without). From the multivariate analysis, sinus rhythm maintenance was the most significant determinant of TR reduction (OR 8.3, 95% CI 1.8 to 37.4). CONCLUSION: In patients with AF with moderate to severe TR, more than two-thirds of patients experienced reduced TR severity, with notable improvements in echocardiographic parameters. Sinus rhythm maintenance was associated with significant TR reduction.

Upper turnaround point in a reentry circuit of the idiopathic left posterior fascicular ventricular tachycardia.

BACKGROUND: The anatomic extent of the reentry circuit in idiopathic left posterior fascicular ventricular tachycardia (LPF-VT) is yet to be fully elucidated. We hypothesized that entrainment mapping could be used to delineate the reentry circuit of an LPF-VT, especially including the upper turnaround point. METHODS: Twenty-three consecutive LPF-VT patients (mean age, 29 ± 9 years, 18 males) were included. We performed overdrive pacing with entrainment attempts at the left bundle branch (LBB) and the left His bundle (HB) region. RESULTS: Overdrive pacing from the LBB region showed concealed fusion in all 23 patients (post-pacing interval [PPI], 322.1 ± 64.3 ms; tachycardia cycle length [TCL], 319.0 ± 61.6 ms; PPI-TCL, 3.1 ± 4.6 ms) with a long stimulus-to-QRS interval (287.9 ± 58.0 ms, approximately 90% of the TCL). Pacing from the same LBB region at a slightly faster pacing rate showed manifest fusion with antidromic conduction to the LBB and minimal in-and-out time to the LBB potential (PPI-TCL, 21.3 ± 13.7 ms). Overdrive pacing from the left HB region showed manifest fusion with a long PPI-TCL (53.9 ± 22.5 ms). CONCLUSIONS: Our pacing study results suggest that the upper turnaround point in a reentry circuit of the LPF-VT may extend to the proximal His-Purkinje conduction system near the LBB region but below the left HB region. The LPF may constitute the retrograde limb of the reentry circuit.

Incidence and Predictors of Severe Tricuspid Regurgitation in Atrial Fibrillation Patients Without Structural Heart Disease.

The long-term effect of atrial fibrillation (AF) on the occurrence of significant tricuspid regurgitation (TR) has not been evaluated in depth yet. We aimed to evaluate the incidence and predictors of severe TR in AF patients without structural heart disease (SHD). In 27,797 patients with AF, after excluding those with severe TR, SHD, implanted cardiac device, and no available follow-up echocardiography, clinical data of 4,613 patients (63.0 ± 11.3 years old, 69.7% male) were evaluated. The primary outcome was the occurrence of severe TR on follow-up echocardiography. Severe TR developed in 164 patients (3.6%) during median follow-up of 2.9 years (interquartile range 1.2 to 5.3). Most of the severe TR (72.6%) developed as isolated TR progression, and the others were associated with SHD progression, most commonly mitral regurgitation (68.9%). Severe TR predominantly occurred in older female patients and those with heart failure (HF), chronic kidney disease, persistent AF (PeAF), larger LA, and a higher degree of baseline TR. Specifically, 0.8%, 3.7%, and 34.4% of patients with no, mild, and moderate baseline TR, respectively, had progressed to severe TR (p <0.001). In multivariable analysis, moderate TR (hazard ratio [HR] 12.52 [8.99 to 17.42]), age ≥65 years (HR 2.25 [1.60 to 3.16]), previous HF (HR 1.79 [1.13 to 2.85]), PeAF (HR 1.54 [1.07 to 2.22]), and female gender (HR 1.52 [1.11 to 2.07]) were independent predictors. In conclusion, 3.6% of patients with AF developed severe TR over long-term follow-up, with moderate TR, age, previous HF, PeAF, and female gender as independent predictors.

Clinical benefits and risks of anticoagulation therapy according to the degree of chronic kidney disease in patients with atrial fibrillation.

BACKGROUND: The clinical benefits and risks of anticoagulation therapy in patients with chronic kidney disease (CKD) are still inconclusive. We describe the outcomes of patients with atrial fibrillation (AF) after anticoagulation therapy according to differences in creatinine clearance (CrCl). We also aimed to determine the patients who could benefit from anticoagulation therapy. METHODS: This is a retrospective observational review of patients with AF who were managed at Asan Medical Center (Seoul, Korea) between January 1, 2006, and December 31, 2018. Patients were categorized into groups according to their baseline CrCl by Cockcroft-Gault equation and their outcomes were evaluated (CKD 1, ≥ 90 mL/min; CKD2, 60-89 mL/min; CKD3, 30-59 mL/min; CKD4, 15-29 mL/min; CKD 5, < 15 mL/min). The primary outcome was NACE (net adverse clinical events), defined as a composite of all-cause mortality, thromboembolic events, and major bleeding. RESULTS: We identified 12,714 consecutive patients with AF (mean 64.6 ± 11.9 years, 65.3% male, mean CHA2DS2-VASc score 2.4 ± 1.6 points) between 2006 and 2017. In patients receiving anticoagulation therapy (n = 4447, 35.0%), warfarin (N = 3768, 84.7%) was used more frequently than NOACs (N = 673, 15.3%). There was a higher 3-year rate of NACE with renal function deterioration (14.8%, 18.6%, 30.3%, 44.0%, and 48.8% for CKD stages 1-5, respectively).The clinical benefit of anticoagulation therapy was most prominent in patients with CKD 1 (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.37-0.67), 2 (HR 0.64 CI 0.54-0.76), and 3 (HR 0.64 CI 0.54-0.76), but not in CKD 4 (HR 0.86, CI 0.57-1.28) and 5 (HR 0.81, CI 0.47-1.40). Among patients with CKD, the benefit of anticoagulation therapy was only evident in those with a high risk of embolism (CHA2DS2-VASc score ≥ 4, HR 0.25, CI 0.08-0.80). CONCLUSION: Advanced CKD is associated with a higher risk of NACE. The clinical benefit of anticoagulation therapy was reduced with the increasing CKD stage.

Oral anticoagulants and concurrent rifampin administration in tuberculosis patients with non-valvular atrial fibrillation.

BACKGROUND: Evidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited. METHODS: Using the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes. RESULTS: Of the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48-1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40-1.00; P = 0.0499). CONCLUSIONS: In our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.

Ventricular tachyarrhythmia treatment and prevention by subthreshold stimulation with stretchable epicardial multichannel electrode array.

The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead is incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting in pain, myocardial damage, and recurrences of ventricular tachyarrhythmia (VTA). We present a method for VTA treatment based on subthreshold electrical stimulations using a stretchable epicardial multichannel electrode array, which does not disturb the normal contraction or electrical propagation of the ventricle. In rabbit models with myocardial infarction, the infarction was detected by mapping intracardiac electrograms with the stretchable epicardial multichannel electrode array. Then, VTAs could be terminated by sequential electrical stimuli from the epicardial multichannel electrode array beginning with low-energy subthreshold stimulations. Last, we used these subthreshold stimulations to prevent the occurrence of additional VTAs. The proposed protocol using the stretchable epicardial multichannel electrode array provides opportunities toward the development of innovative methods for painless ICD therapy.

Temporal change in repolarization parameters after surgical correction of valvular heart diseases.

BACKGROUND: Ventricular tachyarrhythmia is a potentially fatal outcome of cardiac surgery. Abrupt changes in the hemodynamics after surgical correction of valvular heart disease (VHD) can lead to alterations in ventricular repolarization. We compared the difference between temporal changes in repolarization parameters after correction of left-sided VHD. METHODS: We retrospectively analyzed the electrograms of patients who underwent surgical correction of isolated VHD between 2006 and 2015 at Asan Medical Center, including mitral stenosis (MS), mitral regurgitation (MR), aortic stenosis (AS), and aortic regurgitation (AR). Ventricular repolarization parameters were measured at pre-specified time intervals after index surgery using a custom-made ECG analysis program. We compared repolarization parameters, including QT and corrected QT intervals, T peak-to-end interval, and corrected T peak-to-end interval. RESULTS: Analysis of 8265 ECGs from 2110 patients (266 MS, 1059 MR, 421 AS, and 364 AR) was performed. Patients with AS were characterized by older age and more comorbidities than other VHDs. The corrected QT interval showed a peak value immediately after surgery and decreased thereafter in the AS groups. However, a gradual increase over 1 month after surgery in AR, MS, and MR groups was observed. The corrected T peak-to-end interval increased in the MS and MR groups and was unchanged in the AS and AR groups. CONCLUSIONS: The repolarization parameters of surgery changed dynamically after left-sided valvular surgery. Understanding differential temporal change of repolarization parameters according to the type of VHD would help clinicians avoid fatal arrhythmias related to the repolarization changes.

Controlled Level and Variability of Systolic Blood Pressure on the Risk of Thromboembolic Events in Atrial Fibrillation and Hypertension.

Hypertension is an independent risk factor for thromboembolic events in patients with atrial fibrillation (AF). However, the association between blood pressure (BP) control and thromboembolic events remains under-evaluated in patients with AF. We aimed to identify the relation between BP control and the risk of ischemic stroke and systemic embolism in hypertensive patients with AF. Data on 13,712 consecutive patients with AF (9,505 with and 4,207 without hypertension) were retrospectively analyzed. The hypertensive group was divided into quartiles according to the initial BP, linearly interpolated mean BP, variability independent of the mean of the BP, and time in therapeutic range (<130 mm Hg for systolic BP [SBP] and <80 mm Hg for diastolic BP) during follow-up. The primary outcome was ischemic stroke and systemic embolism. The mean follow-up duration of the study population was median 2.7 years (interquartile range 1.1 to 4.9 years), and the median number of BP measurements was 14 (interquartile range 6 to 25) times. Strictly controlled initial and interpolated mean BP and low variability in controlled BP (variability independent of the mean) were associated with a lower risk of ischemic stroke and systemic embolism for both SBP and diastolic BP. A similar risk was observed in patients with strictly controlled SBP (time in therapeutic range under 130 mm Hg >94%) and those without hypertension. In conclusion, continuous and strict maintenance of SBP under 130 mm Hg with low variability at outpatient clinic follow-up reduces the risk of ischemic stroke and systemic embolism in patients with hypertension and AF.

Effect of Dronedarone in the Treatment of Atrial Fibrillation in the Asian Population: Post Hoc Analysis of the ATHENA Trial.

PURPOSE: Limited data are available on the impact of dronedarone treatment in Asian patients with atrial fibrillation (AF) or atrial flutter (AFL). This post hoc analysis evaluated the efficacy and safety of dronedarone compared with placebo in populations from Asian and non-Asian regions randomized in the ATHENA trial (A Placebo-Controlled, Double-blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of CV Hospitalization or Death From Any Cause in Patients With AF/AFL). METHODS: Time to first hospitalization for cardiovascular events or death from any cause (primary outcome) and time to first AF/AFL event recurrence (secondary outcome) were analyzed by Kaplan-Meier curves and Cox proportional hazards regression. FINDINGS: The risk of experiencing the primary composite outcome was significantly lower in the dronedarone-treated patients in both the Asian (hazard ratio = 0.541; 95% CI, 0.320-0.914]) and non-Asian (hazard ratio = 0.768; 95% CI, 0.696-0.848) populations than in the placebo-treated patients. The median time to the first AF/AFL event recurrence was longer in the dronedarone-treated population than in the placebo-treated populations: 183 vs 92 days (P = 0.165) in the Asian population and 534 vs 196 days (P < 0.001) in the non-Asian population. Treatment-emergent adverse events in Asian (81.2% vs 78.4%) and non-Asian (71.4% vs 68.7%) populations and serious treatment-emergent adverse events in Asian (14.3% vs 15.7%) and non-Asian (20.3% vs 21.5%) patients were comparable in patients taking dronedarone compared with those taking placebo. IMPLICATION: Efficacy and tolerability of dronedarone were consistent in the Asian population compared with the non-Asian population in the ATHENA trial. These finding may aid Asian health care professionals to select the appropriate first-line treatment for Asian patients with AF/AFL.

Effect of Sodium-Glucose Cotransporter Inhibitors on Major Adverse Cardiovascular Events and Hospitalization for Heart Failure in Patients With Type 2 Diabetes Mellitus and Atrial Fibrillation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to lower cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risks. Here, we aimed to evaluate the effect of SGLT2 inhibitors on major adverse cardiovascular events (MACE), a composite of cardiovascular mortality, myocardial infarction, or ischemic stroke and hospitalization for heart failure in patients with T2DM and atrial fibrillation (AF). Using the Korean National Health Insurance Service database, we identified 40,268 patients with T2DM and AF who were newly prescribed oral hypoglycemic drugs (2,977 patients with SGLT2 inhibitors and 37,291 patients without SGLT2 inhibitors) between 2014 and 2018. After 1: 4 propensity score matching, patients who received SGLT2 inhibitors (n = 2,958) and those who did not receive SGLT2 inhibitors (n = 10,691) were enrolled, and followed up until December 31, 2018. During a mean follow-up duration of 2.1 ± 1.4 years, the risk of major adverse cardiovascular events was similar between the 2 groups (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.76 to 1.21). There were no significant differences between the 2 groups for cardiovascular mortality, myocardial infarction, or ischemic stroke. However, patients who received SGLT2 inhibitors had significantly lower risks of hospitalization for heart failure (HR 0.70, 95% CI 0.53 to 0.93) and all-cause mortality (HR 0.74, 95% CI 0.56 to 0.98) than those who did not receive SGLT2 inhibitors. In conclusion, in this real-world cohort of Asian patients with T2DM and AF, use of SGLT2 inhibitors was associated with a lower risk of hospitalization for heart failure.

Multiple electrocardiogram generator with single-lead electrocardiogram.

BACKGROUND AND OBJECTIVE: Electrocardiogram (ECG) is measured in various ways. The three main ECG measurement methods include resting ECG, Holter monitoring, and treadmill method. In standard ECG measurement methods, multiple electrodes are attached to the limb and chest. Limb and chest leads measure the frontal and sagittal planes of the heart, respectively. In this case, ECG signals are measured briefly up to 10 seconds. To measure ECG signals based on a single lead, wearable devices have been developed that could measure long-term ECG signals daily. ECG signals are vectors in the heart, which is a three-dimensional structure. Therefore, a single-lead measurement lacks detailed information. The objective of this study was to synthesize multiple ECGs from a single-lead ECG using a generative adversarial network (GAN). METHODS: We trained our model with two independent datasets and one combined dataset. For experiment 1, the PTB-XL dataset was used as the training set, and the China dataset was used as the test set. For experiment 2, the China dataset was used as the training set, and the PTB-XL was used as the test set. Optimized GAN models were obtained for each experiment and evaluated. RESULTS: The Fréchet distance (FD) score and mean squared error (MSE) were used for evaluation. The FD and MSE scores for experiments 1 and 2 were 7.237 and 0.024, and 8.055 and 0.011, respectively. CONCLUSION: We proposed a method to overcome the limitations of modern ECG measurement methods. Low FD and MSE scores not only indicate the possibility but also the similarity between synthesized ECG and reference ECG when compared in ECG paper format. This indicates that the proposed method can be applied to wearable devices that measure single-lead ECG.

Comparison of Dabigatran Versus Warfarin Treatment for Prevention of New Cerebral Lesions in Valvular Atrial Fibrillation.

Warfarin is the standard anticoagulation therapy for valvular atrial fibrillation (AF); however, new oral anticoagulants have emerged as an alternative. We compared the efficacy and safety of dabigatran with conventional treatment in AF associated with left-sided valvular heart disease (VHD), including mitral stenosis (MS). Patients with AF and left-sided VHD were randomly assigned to receive dabigatran or conventional treatment. The primary end point was the occurrence of clinical stroke or a new brain lesion (silent brain infarct and microbleed) on 1-year follow-up brain magnetic resonance imaging. Patients in the dabigatran group were switched from warfarin (n = 52), antiplatelets alone (n = 5), or no therapy (n = 2) to dabigatran. In the conventional group, 53 used warfarin (including 42 MS patients), and 7 used antiplatelets. No death or clinical stroke event occurred in either group during follow-up. Silent brain infarct and microbleed occurred in 20 and 2 patients in the dabigatran group and 20 and 4 patients in the conventional treatment group. The incidence rate of the primary end point did not significantly differ between groups (34% vs 40%, relative risk 0.87, 95% confidence interval 0.59 to 1.29, p = 0.491). The primary end point rate was similar between groups in 82 patients (40 in the dabigatran group and 42 in the conventional group) with MS (32% vs 34%, relative risk 0.93, 95% confidence interval: 0.57 to 1.50, p = 0.759). In conclusion, primary end point rates after treatment with dabigatran were similar to conventional treatment in patients with significant VHD and AF. New oral anticoagulants could be a reasonable alternative to warfarin in patients with AF and VHD, which should be confirmed in future large-scale studies.