Outcomes of Watchful Waiting Strategy and Predictors of Postoperative Prognosis in Asymptomatic or Equivocally Symptomatic Chronic Severe Aortic Regurgitation With Preserved Left Ventricular Function.

BACKGROUND: The optimal surgical timing for asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction remains controversial. METHODS AND RESULTS: Two hundred ten consecutive patients (median age 65 years) with asymptomatic or equivocally symptomatic chronic severe aortic regurgitation and left ventricular ejection fraction ≥50% were registered. First, the treatment plans (aortic valve replacement or watchful waiting) after initial diagnosis were investigated. Then, 2 studies were set: Study A (n=144) investigated the prognosis of patients who were managed under the watchful waiting strategy after initial diagnosis; Study B (n=99) investigated the postoperative prognosis in patients who underwent aortic valve replacement at initial diagnosis or after watchful waiting. The primary outcomes were all-cause death in Study A and postoperative cardiovascular events in Study B. In Study A, 3 died of noncardiovascular causes during a median follow-up of 3.2 years. In Kaplan-Meier analysis, the survival curve was similar to that of an age-sex-matched general population in Japan. In Study B, 9 experienced the primary outcome during a median follow-up of 5.0 years. In Cox regression analysis, preoperative left ventricular end-systolic diameter enlargement (hazard ratio, 1.11; P=0.048) and left ventricular end-systolic diameter >45 mm (hazard ratio, 12.75; P=0.02) were significantly associated with poor postoperative prognosis. In Kaplan-Meier analysis, left ventricular end-systolic diameter >45 mm predicted a higher risk of the primary outcome (P <0.01). CONCLUSIONS: Watchful waiting was achieved safely in asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction. Preoperative left ventricular end-systolic diameter >45 mm predicted a poor postoperative outcome and may be an optimal cut-off value for surgical indication.

Elevated B-Type Natriuretic Peptide Level as a Residual Risk Factor for Ventricular Arrhythmias Among Patients Undergoing Cardiac Resynchronization Therapy With Improved Left Ventricular Ejection Fraction.

Background: Patients who achieve improved left ventricular ejection fraction (LVEF >35%) with cardiac resynchronization therapy (CRT) are at a lower risk of ventricular arrhythmia (VA). Little is known about the significance of the B-type natriuretic peptide (BNP) level for the risk of VA. This study investigated the risk factors for VA in CRT and the risk stratification of VA with BNP in CRT with improved LVEF. Methods and Results: This study evaluated 352 CRT patients from 2012 to 2020. Patients were categorized into 2 groups: improved LVEF (impEF; LVEF >35%), and low LVEF (lowEF; LVEF ≤35%). The serum BNP levels 6 months after CRT device implantation were measured. The primary endpoint was defined as VA requiring treatment with anti-tachycardia pacing or shock or persisting for ≥30 s. Overall, 102 patients had improved LVEF. The impEF group had a significantly lower VA risk than the lowEF group. Patients with low BNP had a lower VA risk than those with high BNP; however, no significant difference was observed between patients with high BNP and those in the lowEF group. Univariate analysis revealed that high BNP was a predictor of VA in the impEF group. Conclusions: The VA risk is reduced with improved LVEF after CRT but not with high BNP levels. The post-BNP level after CRT implantation is a useful marker for predicting VA in patients with improved LVEF.

Assessment of the safety and efficacy of catheter ablation for atrial fibrillation in very elderly patients: insight from the national prospective registry study.

BACKGROUND AND AIMS: This study evaluated the safety and efficacy of catheter ablation in treating atrial fibrillation (AF) among the elderly population. METHODS: A total of 170 017 AF ablation procedures prospectively enrolled from 482 facilities between 2017 and 2020 were analysed. They were stratified into six age groups, ranging from < 65 to ≥ 85 years, in 5-year increments. A cut-off of 80 years was set for dividing participants into two groups. The primary endpoints included procedure-related complications and 1-year arrhythmia recurrence after a 3-month blanking period. RESULTS: Patients ≥ 80 years constituted 7.2% of procedures in 2017, which significantly increased to 9.6% by 2020 (p < 0.001). This older group predominantly comprised women, with smaller stature and body mass index, a higher prevalence of paroxysmal AF, and a higher rate of initial ablation procedures. The overall complication rate was 2.8%, showing a positive correlation with age (p < 0.001), peaking at 4.3% for patients ≥ 85 years. Older age remained a significant independent risk factor for complications (odds ratio: 1.36 [1.24, 1.49], p < 0.001). Cardiac tamponade, ischemic stroke, and sick sinus syndrome were more common in the elderly. The recurrence rate in the total population was 16.0% and did not differ significantly between age groups (log-rank p = 0.473), remaining consistent even after adjusting for multiple variables. CONCLUSIONS: Although age increases complication risk, recurrence rates remained steady across age groups, suggesting that AF ablation is a reasonable option for elderly individuals, contingent on careful patient selection for safety. (ClinicalTrials.gov: NCT03729232).

Implantable loop recorder uncovered torsades de pointes in long-QT syndrome type 1 with multi cause of syncope.

An implantable loop recorder (ILR) is now widely used for differential diagnosis of unexplained syncope or recurrent syncope with unknown causes. In the inherited arrhythmia syndromes, ILR may be useful for management of the therapeutic strategies; however, there is no obvious evidence to uncover arrhythmic syncope by ILR in long-QT syndrome (LQTS) patients. Here we experienced a 19-year-old female patient with LQTS type 1 who had recurrent syncope even after beta-blocker therapy but no arrhythmias were documented, and some episodes might be due to non-cardiogenic causes. Implantable cardioverter defibrillator (ICD) therapy was also recommended; however, she could not accept ICD but was implanted with ILR for further continuous monitoring. Two years later, she suffered syncope during a brief run, and ILR recorded an electrocardiogram at that moment. Thus a marked QT interval prolongation as well as T-wave alternance resulting in development of torsades de pointes could be detected. Although ILR is just a diagnostic tool but does not prevent sudden cardiac death, most arrhythmic events in LQTS are transient and sometimes hard to be diagnosed as arrhythmic syncope. ILR may provide direct supportive evidence to select the optimal therapeutic strategy in cases where syncope is difficult to diagnose. Learning objective: Long-QT syndrome (LQTS) patients often suffer recurrent syncope even after beta-blocker therapy, but torsades de pointes (TdP) is not always detected by standard 12­lead electrocardiogram or Holter monitoring, and some syncope might be non-cardiogenic. In this case, implantable loop recorder (ILR) documented the evidence of QT interval prolongation and beat-by-beat T-wave alternance subsequent TdP. Thus, ILR may provide useful evidence for the optimal treatment strategy in LQTS cases where syncope is difficult to diagnose.

SMART Pass automatic deactivation of subcutaneous implantable cardioverter-defibrillators.

BACKGROUND: The SMART Pass algorithm for subcutaneous implantable cardioverter-defibrillator prevents inappropriate shocks due to oversensing. The mechanisms and significance of SMART Pass deactivation remain unclear. OBJECTIVE: The objective of this study was to assess whether SMART Pass deactivation is associated with inappropriate shocks and to elucidate the underlying mechanism. METHODS: We retrospectively investigated 115 patients who underwent subcutaneous implantable cardioverter-defibrillator implantation between 2016 and 2021. SMART Pass deactivation and inappropriate shocks during follow-up were assessed. The QRS amplitudes of the subcutaneous (S-ECG) and 12-lead electrocardiogram (ECG) at the time of implantation (pre) and SMART Pass deactivation (post) were measured. The patients were divided into the SP-ON group with SMART Pass consistently on and the SP-OFF group with the experience of SMART Pass deactivation. RESULTS: Three of 12 patients in the SP-OFF group experienced inappropriate shocks during a median follow-up of 1094 (interquartile range, 887-1502) days compared with 4 of 87 patients in the SP-ON group. Pre- and post-S-ECG QRS amplitudes were significantly lower in the SP-OFF group than in the SP-ON group (both P < .05), despite similar 12-lead ECG QRS amplitude in both groups. A significant temporary drop in the QRS amplitude of the S-ECG led to SMART Pass deactivation (pre-QRS amplitude vs amplitude at deactivation, P = .015; 95% CI, 0.3-1.9). CONCLUSION: The rate of inappropriate shocks was numerically higher after SMART Pass deactivation. A low QRS amplitude in S-ECG was a potential risk factor for SMART Pass deactivation. Careful follow-up and suitable management are required for managing patients with risks of SMART Pass deactivation.

Explainable localization of premature ventricular contraction using deep learning-based semantic segmentation of 12-lead electrocardiogram.

Background: Predicting the origin of premature ventricular contraction (PVC) from the preoperative electrocardiogram (ECG) is important for catheter ablation therapies. We propose an explainable method that localizes PVC origin based on the semantic segmentation result of a 12-lead ECG using a deep neural network, considering suitable diagnosis support for clinical application. Methods: The deep learning-based semantic segmentation model was trained using 265 12-lead ECG recordings from 84 patients with frequent PVCs. The model classified each ECG sampling time into four categories: background (BG), sinus rhythm (SR), PVC originating from the left ventricular outflow tract (PVC-L), and PVC originating from the right ventricular outflow tract (PVC-R). Based on the ECG segmentation results, a rule-based algorithm classified ECG recordings into three categories: PVC-L, PVC-R, as well as Neutral, which is a group for the recordings requiring the physician's careful assessment before separating them into PVC-L and PVC-R. The proposed method was evaluated with a public dataset which was used in previous research. Results: The evaluation of the proposed method achieved neutral rate, accuracy, sensitivity, specificity, F1-score, and area under the curve of 0.098, 0.932, 0.963, 0.882, 0.945, and 0.852 on a private dataset, and 0.284, 0.916, 0.912, 0.930, 0.943, and 0.848 on a public dataset, respectively. These quantitative results indicated that the proposed method outperformed almost all previous studies, although a significant number of recordings resulted in requiring the physician's assessment. Conclusions: The feasibility of explainable localization of premature ventricular contraction was demonstrated using deep learning-based semantic segmentation of 12-lead ECG.Clinical trial registration: M26-148-8.

Clinical Usefulness of the Active Fixation Quadripolar Left Ventricular Lead Compared With the Passive Fixation Quadripolar Lead in Cardiac Resynchronization Therapy.

BACKGROUND: This study compared the stability of the Medtronic Attain Stability Quad (ASQ), a novel quadripolar active fixation left ventricular (LV) lead with a side helix, to that of conventional quadripolar leads with passive fixation (non-ASQ) and evaluated their LV lead performance. METHODS AND RESULTS: In all, 183 consecutive patients (69 ASQ, 114 non-ASQ) who underwent cardiac resynchronization therapy (CRT) between January 2018 and June 2021 were enrolled. Complications, including elevated pacing capture threshold (PCT) levels, phrenic nerve stimulation (PNS), and LV lead dislodgement, were analyzed during the postimplantation period until the first outpatient visit after discharge. The frequency of LV lead-related complications was significantly lower in the ASQ than non-ASQ group (14% vs. 30%, respectively; P=0.019). Specifically, LV lead dislodgement occurred only in the non-ASQ group, and elevated PCT levels were significantly lower in the ASQ group (7% vs. 23%; P=0.007). Kaplan-Meier analysis confirmed a significantly lower incidence of LV lead-related complications in the ASQ group (log-rank P=0.005). Cox multivariable regression analysis showed a significant reduction in lead-related complications associated with ASQ (hazard ratio 0.44; 95% confidence interval 0.23-0.83; P=0.011). CONCLUSIONS: The ASQ group exhibited fewer LV lead-related complications requiring reintervention and setting changes than the non-ASQ group. Thus, the ASQ may be a favorable choice for CRT device implantation.

Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. METHODS: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. RESULTS: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight. CONCLUSIONS: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.

Comparison Between Heart Failure Without Left Ventricular Systolic Dysfunction and Progression to End-Stage in Hypertrophic Cardiomyopathy.

BACKGROUND: The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated. METHODS AND RESULTS: This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD. CONCLUSIONS: In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.

Demonstration of Arrhythmia Substrate-Associated Dispersion of Repolarization by Epicardial Unipolar Mapping in Brugada Syndrome.

BACKGROUND: Epicardial unipolar mapping has not been thoroughly investigated in Brugada syndrome (BrS). OBJECTIVES: This study aims to examine the characteristics of epicardial unipolar potentials in BrS and investigate the differences from overt cardiomyopathy. METHODS: Epicardial mapping was performed in 8 patients with BrS and 6 patients with cardiomyopathy. We investigated the J-wave amplitudes using unipolar recordings at delayed potential (DP) sites via bipolar recordings. The repolarization time (RT) at and around the DP recording sites was measured, and maximum dispersion of the RT divided by the distance was defined as the RT dispersion index. RESULTS: Epicardial mapping at baseline revealed significantly higher J-wave amplitude with bipolar DP in patients with BrS than in patients with cardiomyopathy. J-wave amplitude ≥0.42 mV had 99.1% sensitivity and 100% specificity for diagnosing BrS. The RT dispersion index was significantly higher in patients with BrS than in patients with cardiomyopathy at baseline. In all patients with BrS, coved-type unipolar electrograms without negative T waves (short RT) appeared close to coved-type electrograms with negative T waves (long RT) at the DP recording sites after pilsicainide administration. Thus, a steep RT dispersion was observed in this region, and ventricular arrhythmias emerged from this shorter RT area in all 3 patients with BrS in whom ventricular arrhythmias were induced. CONCLUSIONS: Bipolar DP-related prominent unipolar J waves and steep repolarization gradients may be more specific for characterizing BrS than for overt cardiomyopathy. Ventricular arrhythmias in BrS are associated with a steep repolarization gradient, indicating phase 2 re-entry as a possible cause.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Observational study of frailty in older Japanese patients with non-valvular atrial fibrillation receiving anticoagulation therapy.

The number of patients with atrial fibrillation is increasing, and frailty prevalence increases with age, posing challenges for physicians in prescribing anticoagulants to such patients because of possible harm. The effects of frailty on anticoagulant therapy in older Japanese patients with nonvalvular atrial fibrillation (NVAF) are unclear. Herein, we prescribed rivaroxaban to Japanese patients with NVAF and monitored for a mean of 2.0 years. The primary endpoint was stroke or systemic embolism. The secondary endpoints were all-cause or cardiovascular death, composite endpoint, and major or non-major bleeding. Frailty was assessed using the Japanese long-term care insurance system. A multiple imputation technique was used for missing data. The propensity score (PS) was obtained to estimate the treatment effect of frailty and was used to create two PS-matched groups. Overall, 5717 older patients had NVAF (mean age: 73.9 years), 485 (8.5%) were classified as frail. After PS matching, background characteristics were well-balanced between the groups. Rivaroxaban dosages were 10 and 15 mg/day for approximately 80% and the remaining patients, respectively. Frailty was not associated with the primary endpoint or secondary endpoints. In conclusion, frailty does not affect the effectiveness or safety of rivaroxaban anticoagulant therapy in older Japanese patients with NVAF.Trial registration: UMIN000019135, NCT02633982.