Background: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.

Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13–0.70; P=0.004) than the medical therapy group.

Conclusions: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Background: A novel multielectrode radiofrequency balloon (RFB) catheter has been released for pulmonary vein isolation (PVI).

Methods and Results: In this observational study consecutive patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) undergoing first-time PVI were enrolled in 2 high-volume ablation centers. All procedures were conducted in conjunction with a 3D-mapping system. Clinical, procedural and ablation parameters were systematically analyzed. 105 patients (58% male; 52% paroxysmal AF, 68±11.3 years mean age, left atrial volume index 38.6±14.8 mL/m²) were included. 241/412 (58.5%) PVs were successfully isolated with a single shot (SS), with a time-to-isolation of 11.6±8 s. Total number of radiofrequency applications was 892 (mean 2.2/PV), resulting in successful isolation of 408/412 (99%) PVs at the end of the procedure. Mean electrodes’ impedance drop was significantly higher in the SS-PVI compared with non-SS applications (21.5±6.6 vs. 18.6±6.5 Ohm). Concordantly, higher temperature rise was observed in the SS vs. non-SS applications (10.9±4.9℃ vs. 9.6±4.7℃).

Conclusions: In this multicenter real-world study, mean impedance drop and temperature rise were associated with successful SS-PVI applying the novel RFB catheter. These parameters may help to guide efficient usage of the new RF balloon.

Background: Previous studies on mortality in atrial fibrillation (AF) included a limited number of elderly patients receiving direct oral anticoagulants (DOACs). This subanalysis of the ANAFIE Registry evaluated 2-year mortality according to causes of death of elderly non-valvular AF (NVAF) patients in the DOAC era.

Methods and Results: The ANAFIE Registry was a multicenter prospective observational study. Mean patient age was 81.5 years and 57.3% of patients were male. Of the 32,275 patients completing the study, 2,242 died. The most frequent causes of death were cardiovascular (CV) death (32.4%), followed by infection (17.1%) and malignancy (16.1%). Incidence rates of CV-, malignancy-, and infection-related death were 1.20, 0.60, and 0.63 per 100 person-years, respectively. Patients aged ≥85 years showed increased proportions of non-CV and non-malignancy deaths and a decreased proportion of malignancy deaths compared with patients aged <85 years. The incidence of death due to congestive heart failure/cardiogenic shock, infection, and renal disease was higher in patients aged ≥85 than those aged <85 years. Compared with warfarin, DOACs were associated with a significantly lower risk of death by intracranial hemorrhage, ischemic stroke, and renal disease.

Conclusions: This subanalysis described the mortality according to causes of death of Japanese elderly NVAF patients in the DOAC era. Our results imply that a more holistic approach to comorbid conditions and stroke prevention are required in these patients.

Background: Previous studies revealed a relationship between 8-hydroxy-2′-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).

Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5–10%), stage III (10–20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named ‘DNA methylation on cytosine’ was the only genetic component significantly associated with 8-OHdG concentration.

Conclusions: Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Background: An epicardial connection (EC) between the right-sided pulmonary venous (RtPV) carina and right atrium (RA) may preclude PV isolation, but its electrophysiological role during atrial fibrillation (AF) remains unknown.

Methods and Results: This prospective observational study included 98 consecutive patients undergoing catheter ablation for AF, subdivided into the EC group (n=17) and non-EC group (n=80) based on observation of RA posterior wall breakthrough during RtPV pacing. Mean left atrial (LA) dominant frequency (mean DF_LA) was defined as the averaged DFs at the right and left PVs and LA appendage. The regional DF was higher in the EC group vs. the non-EC group except at the left PV antrum. The DF at the RA appendage (RAA) and mean DF_LAwere equivocal (6.5±0.7 vs. 6.6±0.7 Hz) in the EC group, but the mean DF_LAwas significantly higher than that at the RAA (5.8±0.6 vs. 6.1±0.5 Hz, P=0.001) in the non-EC group, suggesting an LA-to-RA DF gradient. A significant correlation of DF between the RtPV antrum and RAA was observed in the EC group (P<0.001, r=0.84) but not in the non-EC group.

Conclusions: An electrophysiological link via interatrial ECs might attenuate the hierarchical nature of activation frequencies of AF, leading to advanced electrical remodeling of the atria.

Background: Patients with end-stage renal disease on hemodialysis (ESRD-HD) have a lifelong risk of atrial fibrillation-related stroke. We compared clinical outcomes in ESRD-HD patients undergoing coronary artery bypass grafting (CABG) with and without concomitant left atrial appendage (LAA) closure.

Methods and Results: Of 2,783 consecutive patients undergoing isolated CABG between 2002 and 2020, 242 patients had ESRD-HD with sinus rhythm. The primary outcome was a composite of death and stroke. An inverse probability (IP)-weighted cohort was created based on the propensity score. The 2 IP-weighted groups had well-balanced baseline and surgical backgrounds, with an equivalent follow-up. Five-year stroke-free survival was significantly higher in patients with LAA closure (log-rank test, P=0.035). The adjusted hazard ratio of LAA closure for death and stroke was 0.43 (95% confidence interval [CI] 0.20–0.92; P=0.023). Competing risk analysis showed that LAA closure was significantly associated with a risk reduction of stroke (subhazard ratio 0.26; 95% CI 0.08–0.96; P=0.028). No significant difference was observed in adjusted risk ratios for reoperation for bleeding, new atrial fibrillation, 30-day mortality, and readmission for heart failure.

Conclusions: Concomitant LAA closure during CABG can reduce the risk of death and stroke in ESRD-HD patients with normal sinus rhythm.

Background: Cardiac implantable electronic devices (CIED) are very rare in the pediatric population. In children with CIED, transvenous lead extraction (TLE) is often necessary. The course and effects of TLE in children are different than in adults. Thus, this study determined the differences and specific characteristics of TLE in children vs. adults.

Methods and Results: A post hoc analysis of TLE data in 63 children (age ≤18 years) and 2,659 adults (age ≥40 years) was performed. The 2 groups were compared with respect to risk factors, procedure complexity, and effectiveness. In children, the predominant pacing mode was a single chamber ventricular system and lead dysfunction was the main indication for lead extraction. The mean implant duration before TLE was longer in children (P=0.03), but the dwell time of the oldest extracted lead did not differ significantly between adults and children. The duration (P=0.006) and mean extraction time per lead (P<0.001) were longer in children, with more technical difficulties during TLE in the pediatric group (P<0.001). Major complications were more common, albeit not significantly, in children. Complete radiographic and procedural success were significantly lower in children (P<0.001).

Conclusions: TLE in children is frequently more complex, time consuming, and arduous, and procedural success is more often lower. This is related to the formation of strong fibrous tissue surrounding the leads in pediatric patients.

Background: Because the penetration of transvenous lead extraction (TLE) for cardiac implantable electronic device (CIED) infection has not been investigated in Japan, we conducted a population-based, retrospective, descriptive study to evaluate regional disparities in the use of TLE for CIED infection and the potential undertreatment of CIED infection using a nationwide insurance claims database.

Methods and Results: Patients who underwent CIED implantation or generator exchange and TLE between April 2018 and March 2020 were identified. Moreover, the penetration ratio of TLE for CIED infection in each prefecture was estimated. CIED implantation and TLE were most prevalent in the age categories of 80–89 years (40.3%) and 80–89 years (36.9%), respectively. There was no correlation between the number of CIED implantations and that of TLE (rho=−0.087, 95% confidence interval −0.374 to 0.211, P=0.56). The median penetration ratio was 0.00 (interquartile range 0.00–1.29). Of the 47 prefectures, 6, comprising Okinawa, Miyagi, Okayama, Fukuoka, Tokyo, and Osaka, showed a penetration ratio ≥2.00.

Conclusions: Our study data indicated great regional disparities in the penetration of TLE and potential undertreatment of CIED infection in Japan. Additional measures are needed to address these issues.

Background: Brugada syndrome is a potential cause of sudden cardiac death (SCD) and is characterized by a distinct ECG, but not all patients with A Brugada ECG develop SCD. In this study we sought to examine if an artificial intelligence (AI) model can predict a previous or future ventricular fibrillation (VF) episode from a Brugada ECG.

Methods and Results: We developed an AI-enabled algorithm using a convolutional neural network. From 157 patients with suspected Brugada syndrome, 2,053 ECGs were obtained, and the dataset was divided into 5 datasets for cross-validation. In the ECG-based evaluation, the precision, recall, and F₁score were 0.79±0.09, 0.73±0.09, and 0.75±0.09, respectively. The average area under the receiver-operating characteristic curve (AUROC) was 0.81±0.09. On per-patient evaluation, the AUROC was 0.80±0.07. This model predicted the presence of VF with a precision of 0.93±0.02, recall of 0.77±0.14, and F₁score of 0.81±0.11. The negative predictive value was 0.94±0.11 while its positive predictive value was 0.44±0.29.

Conclusions: This proof-of-concept study showed that an AI-enabled algorithm can predict the presence of VF with a substantial performance. It implies that the AI model may detect a subtle ECG change that is undetectable by humans.

Background: Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.

Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1–78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1–44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9–65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group.

Conclusions: Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Background: To assist healthcare providers in interpreting guidelines, clinical questions (CQ) are often included, but not always, which can make interpretation difficult for non-expert clinicians. We evaluated the ability of ChatGPT to accurately answer CQs on the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).

Methods and Results: We conducted an observational study using data from JSH 2019. The accuracy rate for CQs and limited evidence-based questions of the guidelines (Qs) were evaluated. ChatGPT demonstrated a higher accuracy rate for CQs than for Qs (80% vs. 36%, P value: 0.005).

Conclusions: ChatGPT has the potential to be a valuable tool for clinicians in the management of hypertension.