A Novel Risk Score for Major Bleeding in Japanese Patients with Non-Valvular Atrial Fibrillation: The J-RISK AF Study.

AIM: Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF. METHODS: Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3). RESULTS: During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores. CONCLUSION: Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

Preclose Versus Postclose Using Suture-Mediated Vascular Closure System for Catheter Ablation With Femoral Vein Access.

BACKGROUND: Differences in the efficacy and safety between the preclose and postclose suture-mediated vascular closure systems for femoral vein access have not been adequately studied. OBJECTIVES: This study aimed to evaluate the efficacy and safety of these 2 suturing techniques in femoral vein access. METHODS: Patients subjected to elective catheter ablation via the femoral vein using a sheath of 8- to 13-F inner diameter (n = 282) were randomized to the preclose or postclose groups for the single-suture technique using ProGlide/ProStyle (Abbott Vascular). Duplex ultrasound was performed on days 1 and 90 after the procedure to evaluate vascular complications. The primary efficacy endpoint was rebleeding requiring recompression, and the primary safety endpoint was any major complication occurring within 90 days. The secondary efficacy endpoints included time to hemostasis and time to ambulation, and the secondary safety endpoint was any minor complication occurring within 90 days. RESULTS: The preclose group demonstrated a significantly lower rebleeding rate (5 of 141 [3.5%] vs 15 of 141 [10.6%]; P = 0.03) and shorter time to hemostasis (254.0 ± 120.4 seconds vs 299.8 ± 208.2 seconds; P = 0.02) compared with the postclose group. Five patients in each group were lost to follow-up at 90 days. Incidence of major complications were similar in both groups (1 of 136 [0.7%]; P = 1.00), whereas minor complications were observed in 18 of 136 (13.2%) and 21 of 136 (15.4%) patients in the preclose and postclose groups, respectively, without a significant difference (P = 0.73). CONCLUSIONS: In femoral vein access using the single-suture technique with ProGlide/ProStyle, the preclose technique presented a higher hemostasis rate than the postclose technique, without compromising safety.

Detection of Epicardial Connection Through Intercaval Bundle Involving Right Pulmonary Veins After Ipsilateral Circumferential Ablation by Intra-Atrial Activation Sequence Pacing From the Right Pulmonary Vein.

BACKGROUND: An epicardial connection (EC) through the intercaval bundle (EC-ICB) between the right pulmonary vein (RPV) and right atrium (RA) is one of the reasons for the need for carina ablation for PV isolation and may reduce the acute and chronic success of PV isolation. We evaluated the intra-atrial activation sequence during RPV pacing after failure of ipsilateral RPV isolation and sought to identify specific conduction patterns in the presence of EC-ICB. METHODS AND RESULTS: This study included 223 consecutive patients who underwent initial catheter ablation of atrial fibrillation. If the RPV was not isolated using circumferential ablation or reconnected during the waiting period, an exit map was created during mid-RPV carina pacing. If the earliest site on the exit map was the RA, the patient was classified into the EC-ICB group. The exit map, intra-atrial activation sequence, and RPV-high RA time were evaluated. First-pass isolation of the RPV was not achieved in 36 patients (16.1%), and 22 patients (9.9%) showed reconnection. Twelve and 28 patients were classified into the EC-ICB and non-EC-ICB groups, respectively, after excluding those with multiple ablation lesion sets or incomplete mapping. The intra-atrial activation sequence showed different patterns between the 2 groups. The RPV-high RA time was significantly shorter in the EC-ICB than in the non-EC-ICB group (69.2±15.2 versus 148.6±51.2 ms; P<0.001), and RPV-high RA time<89.0 ms was highly predictive of the existence of an EC-ICB (sensitivity, 91.7%; specificity, 89.3%). CONCLUSIONS: An EC-ICB can be effectively detected by intra-atrial sequencing during RPV pacing, and an RPV-high RA time of <89.0 ms was highly predictive.

Hypertrophic Cardiomyopathy Predicts Thromboembolism and Heart Failure in Patients With Nonvalvular Atrial Fibrillation　- A Prospective Analysis From the Hokuriku-Plus AF Registry.

BACKGROUND: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan.Methods and Results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5-5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56-6.21), the CHA2DS2-VASc score (1.35, 1.18-1.54), and concomitant HCM (2.48, 1.16-4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72-4.43), older age (1.07, 1.05-1.10), lower body mass index (0.95, 0.91-0.99), a history of HF (2.49, 1.77-3.52), and lower left ventricular ejection fraction (0.98, 0.97-0.99) were significantly associated with the development of HF. CONCLUSIONS: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.

Mechanisms of fever-induced QT prolongation and torsades de pointes in patients with KCNH2 mutation.

AIMS: Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP). METHODS AND RESULTS: We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C. CONCLUSION: These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.

The utility of zebrafish cardiac arrhythmia model to predict the pathogenicity of KCNQ1 variants.

Genetic testing for inherited arrhythmias and discriminating pathogenic or benign variants from variants of unknown significance (VUS) is essential for gene-based medicine. KCNQ1 is a causative gene of type 1 long QT syndrome (LQTS), and approximately 30% of the variants found in type 1 LQTS are classified as VUS. We studied the role of zebrafish cardiac arrhythmia model in determining the clinical significance of KCNQ1 variants. We generated homozygous kcnq1 deletion zebrafish (kcnq1del/del) using the CRISPR/Cas9 and expressed human Kv7.1/MinK channels in kcnq1del/del embryos. We dissected the hearts from the thorax at 48 h post-fertilization and measured the transmembrane potential of the ventricle in the zebrafish heart. Action potential duration was calculated as the time interval between peak maximum upstroke velocity and 90% repolarization (APD90). The APD90 of kcnq1del/del embryos was 280 ± 47 ms, which was significantly shortened by injecting KCNQ1 wild-type (WT) cRNA and KCNE1 cRNA (168 ± 26 ms, P < 0.01 vs. kcnq1del/del). A study of two pathogenic variants (S277L and T587M) and one VUS (R451Q) associated with clinically definite LQTS showed that the APD90 of kcnq1del/del embryos with these mutant Kv7.1/MinK channels was significantly longer than that of Kv7.1 WT/MinK channels. Given the functional results of the zebrafish model, R451Q could be reevaluated physiologically from VUS to likely pathogenic. In conclusion, functional analysis using in vivo zebrafish cardiac arrhythmia model can be useful for determining the pathogenicity of loss-of-function variants in patients with LQTS.

Prediction of atrioventricular conduction disturbance after ablation of persistent atrial fibrillation.

The prevalence of atrioventricular conduction disturbance (AVCD) in patients with persistent atrial fibrillation (AF) has not yet been fully investigated. We sought to identify the predictors of AVCD in patients with AF by analyzing the relationship between pre-ablation heart rate during AF and the PR interval in sinus rhythm after ablation. We analyzed pre-ablation 24-h Holter electrocardiogram (ECG) and 12 lead ECG 12 months after ablation of 121 consecutive patients with persistent AF who underwent their first ablation procedure and maintained sinus rhythm at 12 months. AVCD was defined as a first-degree atrioventricular block (AVB), second-degree AVB, high-degree AVB, or third-degree AVB observed on ECG at 12 months after ablation. Seventeen out of 121 patients (14.0%) had AVCD at 12 months. In the group with AVCD, total heartbeat (THB) and maximum heart rate (Max HR) were significantly lower, and the prevalence of concomitant Cavo-tricuspid isthmus-dependent atrial flutter before ablation and the appearance of macro reentrant atrial tachycardia (AT) during the procedure were significantly higher than those in the group without AVCD. Multiple regression analysis revealed that maximum HR and macro reentrant AT were significant predictors of AVCD. Receiver operating characteristic curve analysis revealed that Max HR of <165.0 bpm predicts AVCD with a sensitivity of 76.47% and a specificity of 74.00%. In patients with persistent AF, low Max HR and the presence of macro reentrant AT during the ablation procedure were predictors of AVCD.

Ablation index-guided high-power vs. moderate-power cavotricuspid isthmus ablation.

Ablation index (AI)-guided ablation is useful for pulmonary vein isolation (PVI) and cavotricuspid isthmus (CTI) ablation. However, the impact of radiofrequency (RF) application power on CTI ablation with a fixed target AI remains unclear. One-hundred-thirty drug-refractory atrial fibrillation and/or atrial flutter patients who underwent AI-guided CTI ablation with or without PVI between July 2020 and August 2021 were randomly assigned to high-power (45 W) and moderate-power (35 W) groups. We performed CTI ablation with the same target AI value in both groups: 500 for the anterior 1/3 segments and 450 for the posterior 2/3 segments. In total, first-pass conduction block of the CTI was obtained in 111 patients (85.4%), with 7 patients (5.4%) showing CTI reconnection. The rate of first-pass conduction block was significantly higher in the 45 W group (61/65, 93.8%) than in the 35 W group (50/65, 76.9%, P = 0.01). CTI ablation and CTI fluoroscopy time were significantly shorter in the 45 W group than in the 35 W group (CTI ablation time: 192.3 ± 84.8 vs. 319.8 ± 171.4 s, P < 0.0001; CTI fluoroscopy time: 125.2 ± 122.4 vs. 171.2 ± 124.0 s, P = 0.039). Although there was no significant difference, steam pops were identified in two patients from the 45 W group at the anterior segment of the CTI. The 45 W ablation strategy was faster and provided a higher probability of first-pass conduction block than the 35 W ablation strategy for CTI ablation with a fixed AI target.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

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.

Characterization of baseline clinical factors associated with incident worsening kidney function in patients with non-valvular atrial fibrillation: the Hokuriku-Plus AF Registry.

Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0 years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 from the Hokuriku-Plus AF Registry. The primary outcome was incident WKF, defined as the %eGFR change from the baseline ≥ 30% during the follow-up period. We evaluated the association between baseline variables and incident WKF using univariate and multivariate Cox proportional hazard models. We also evaluated the non-linear association between the identified factors and incident WKF. During a median follow-up period of 3.0 years (interquartile range: 2.7-3.3), incident WKF was observed in 108 patients (32.6 per 1000 person-years). Compared to the patients without incident WKF, the patients with incident WKF were older and had a higher prevalence of heart failure (HF), diabetes mellitus (DM), and vascular disease at baseline. Those who experienced incident WKF also had higher diastolic blood pressure, lower hemoglobin, lower eGFR, higher B-type natriuretic peptide (BNP) and used warfarin more frequently. Upon multivariate analysis, age ≥ 75 years, HF, DM, and anemia were independently associated with incident WKF. Additionally, age and hemoglobin were linearly associated with the risk of incident WKF, whereas a J- or U-shaped association was observed for HbA1c and BNP. Age ≥ 75 years, HF, DM, and anemia were associated with the development of WKF in Japanese patients with NVAF. In patients with these risk factors, a careful monitoring of the kidney function and appropriate interventions may be important when possible.

Impact of baseline blood pressure on adverse outcomes in Japanese patients with non-valvular atrial fibrillation: the J-RISK AF.

Aims: This study aimed to investigate the impact of baseline blood pressure (BP) on adverse outcomes in patients with atrial fibrillation (AF), using a pooled analysis performed on data from J-RISK AF, a large-scale cohort of Japanese patients with AF. Methods and results: Of the 16 918 patients from five major AF registries including the J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry, 15 019 non-valvular AF (NVAF) patients with baseline BP values (age, 70.0 ± 11.0 years; men, 69.1%) were analysed. Incidence rates of adverse events were evaluated between patients divided into baseline systolic BP quartiles or at 150 mmHg. During the follow-up period of 730 days, ischaemic stroke, major bleeding, all-cause death, and cardiovascular death occurred in 277, 319, 718, and 275 patients, respectively. Hazard ratios (HRs) for ischaemic stroke and major bleeding were comparable among the quartiles, whereas HRs for all-cause and cardiovascular deaths in the lowest quartile with systolic BP <114 mmHg were significantly higher [HR 1.43, 95% confidence interval (CI) 1.13-1.81; and HR 1.47, 95% CI 1.01-2.12, respectively] than in the third quartile, even after adjusting for known confounding factors. In patients with a systolic BP of ≥150 mmHg, adjusted HR for major bleeding was significantly higher than that of <150 mmHg (HR 1.64, 95% CI 1.12-2.40). Conclusion: In Japanese patients with NVAF, a baseline systolic BP <114 mmHg was significantly associated with higher all-cause and cardiovascular mortality. In contrast, a systolic BP ≥150 mmHg was an independent risk factor for major bleeding.

Clinical Characteristics, Outcomes, and Risk Factors for Adverse Events in Elderly and Non-Elderly Japanese Patients With Non-Valvular Atrial Fibrillation　- Competing Risk Analysis From the Hokuriku-Plus AF Registry.

Background: Few studies in Japan have reported on follow-up data regarding the clinical course and risk factors for adverse outcomes in elderly patients with non-valvular atrial fibrillation (NVAF), vs. younger patients, when considering the competing risk of death. Methods and Results: We prospectively studied 1,328 patients with NVAF (965 men; mean [±SD] age 72.4±9.7 years) from the Hokuriku-Plus AF Registry with a median follow-up of 5.0 years (interquartile range 3.5-5.3 years) and evaluated the incidence of thromboembolism or major bleeding in elderly (age ≥75 years; n=595) and non-elderly (age <75 years; n=733) patients. Analysis using the Gray method showed no significant difference in the incidence of thromboembolism; however, the incidence of major bleeding was significantly higher in the elderly than non-elderly group. The Fine-Gray model, after adjustment for age and sex in the elderly group, showed that age (hazard ratio [HR] 1.08; 95% confidence interval [CI] 1.02-1.13; P=0.004) and warfarin use (HR 1.87; 95% CI 1.12-3.14; P=0.02) were significantly associated with major bleeding. In the elderly group, those using warfarin had a higher incidence of thromboembolism and major bleeding than those using direct oral anticoagulants (DOACs). Conclusions: The efficacy and safety of DOACs were remarkable in elderly compared with non-elderly patients with NVAF considering the competing risk of death. DOACs may be a favorable choice in elderly patients with NVAF.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Association between Cardiovascular Health and Incident Atrial Fibrillation in the General Japanese Population Aged ≥40 Years.

This study explores the association between lifestyle behavior and incident atrial fibrillation (AF) in the general Japanese population. Japanese residents aged ≥40 years undergoing a national health checkup in Kanazawa City were included. We hypothesized that better lifestyle behavior is associated with lower incidence of AF. Lifestyle behavior was evaluated by the total cardiovascular health (CVH) score (0 = poor to 14 = ideal), calculated as the sum of the individual scores on seven modifiable risk factors: smoking status, physical activity, obesity, patterns of eating schedule, blood pressure, total cholesterol, and blood glucose. The association between CVH and incident AF was assessed, adjusting for other factors. A total of 37,523 participants (mean age 72.3 ± 9.6 years, 36.8% men, and mean total CVH score 9 ± 1) were analyzed. During the median follow-up period of 5 years, 703 cases of incident AF were observed. Using a low CVH score as a reference, the upper group (ideal CVH group) had a significantly lower risk of incident AF (hazard ratio [HR] = 0.79, 95% confidence interval 0.65-0.96, p = 0.02), especially among those aged <75 years (HR = 0.68, 95% confidence interval 0.49-0.94, p = 0.02). Thus, ideal CVH is independently associated with a lower risk for incident AF, particularly in younger Japanese individuals (<75 years).

A Novel Risk Stratification System for Ischemic Stroke in Japanese Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Recently, identification of independent risk factors for ischemic stroke in Japanese non-valvular atrial fibrillation (NVAF) patients was made by analyzing the 5 major Japanese registries: J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and the Hokuriku-Plus AF Registry.Methods and Results:The predictive value of the risk scheme in Japanese NVAF patients was assessed. Of 16,918 patients, 12,289 NVAF patients were analyzed (mean follow up, 649±181 days). Hazard ratios (HRs) of each significant, independent risk factor were determined by using adjusted Cox-hazard proportional analysis. Scoring system for ischemic stroke was created by transforming HR logarithmically and was estimated by c-statistic. During the 21,820 person-years follow up, 241 ischemic stroke events occurred. Significant risk factors were: being elderly (aged 75-84 years [E], HR=1.74), extreme elderly (≥85 years [EE], HR=2.41), having hypertension (H, HR=1.60), previous stroke (S, HR=2.75), type of AF (persistent/permanent) (T, HR=1.59), and low body mass index <18.5 kg/m2(L, HR=1.55) after adjusting for oral anticoagulant treatment. The score was assigned as follows: 1 point to H, E, L, and T, and 2 points to EE and S (HELT-E2S2score). The C-statistic, using this score, was 0.681 (95% confidence interval [CI]=0.647-0.714), which was significantly higher than those using CHADS2(0.647; 95% CI=0.614-0.681, P=0.027 for comparison) and CHA2DS2-VASc scores (0.641; 95% CI=0.608-0.673, P=0.008). CONCLUSIONS: The HELT-E2S2score may be useful for identifying Japanese NVAF patients at risk of ischemic stroke.

Transient swallowing-induced atrial tachycardia in a patient with genotyped hypertrophic cardiomyopathy.

Most cases of swallowing-induced atrial tachycardia require radiofrequency catheter ablation for a permanent cure; however, the arrhythmia subsided after temporary prescription of verapamil in a patient with genotyped hypertrophic cardiomyopathy.

Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design.

INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data-and in particular multicentre data-exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds. METHODS AND ANALYSIS: The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies. ETHICS AND DISSEMINATION: This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000038210.

Prolongation of QT interval after pulmonary vein isolation for paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary vein isolation (PVI) affects the ganglionated plexi (GP) around the atrium leading to a modification of intrinsic cardiac autonomic system (ANS). In animal models, GP ablation has the potential risk of QT prolongation and ventricular arrhythmias. However, the impact of PVI on QT intervals in human remains unclear. METHODS AND RESULTS: We analyzed electrocardiograms of 117 consecutive patients with paroxysmal atrial fibrillation (AF) who underwent their first PVI procedures and maintained sinus rhythm without antiarrhythmic drugs at all evaluation points (4 h, 1 day, 1 month, and 3 months after PVI). Heart rate significantly increased at 4 h, 1 day, and 1 month. Raw QT interval prolonged at 4 h (417.1 ± 41.6 ms, p < .001) but shortened at 1 day (376.4 ± 34.1 ms, p < .001), 1 month (382.2 ± 31.5 ms, p < 0.001), and 3 months (385.1 ± 32.8 ms, p < 0.001) compared with baseline (391.6 ± 31.4 ms). Bazett-corrected QTc intervals were significantly prolonged at 4 h (430.8 ± 27.9 ms, p < .001), 1 day (434.8 ± 22.3 ms, p < .001), 1 month (434.8 ± 22.3 ms, p < .001), and 3 months (420.1 ± 21.8 ms, p < .001) compared with baseline (404.9 ± 25.2 ms). Framingham-corrected QTc intervals significantly prolonged at 4 h (424.1 ± 26.6 ms, p < .001) and 1 day (412.3 ± 29.3 ms, p < .01) compared with baseline (399.2 ± 22.7 ms). Multiple regression analysis revealed that female sex is a significant predictor of raw QT and QTc interval increase at 4 h after PVI. CONCLUSION: Raw QT and QTc were prolonged after PVI, especially in the acute phase. Female sex is a risk factor for QT increase.

Risk Factors Associated With Ischemic Stroke in Japanese Patients With Nonvalvular Atrial Fibrillation.

Importance: Despite the development of risk stratification schemes that have been widely used to determine the risk for thromboembolism in patients with nonvalvular atrial fibrillation (NVAF), risk stratification schemes in Asian patients with NVAF remain undetermined. Objective: To determine risk factors for ischemic stroke in Japanese patients with NVAF. Design, Setting, and Participants: This cohort study analyzed individual patient data from 5 AF registries in Japan: J-RHYTHM (Japanese Rhythm Management Trial for Atrial Fibrillation) Registry, Fushimi AF Registry, Shinken Database, Keio Interhospital Cardiovascular Studies (Keio Study), and Hokuriku-Plus AF Registry. Patients with atrial fibrillation were registered from 158 institutions in the J-RHYTHM Registry, 80 in the Fushimi AF Registry, a single hospital in Shinken Database, 11 in the Keio Study, and 19 in the Hokuriku-Plus AF Registry. Patients with valvular AF or lacking data were excluded. Data were collected and integrated in March 2016, and those from the Keio Study were updated in April 2018. Data were analyzed from April 2018 to February 2020. Main Outcomes and Measures: Significant risk factors for ischemic stroke were determined by adjusted Cox proportional hazards analysis. Results: In total, 12 289 patients with NVAF (3758 [31%] female; mean [SD] age 70.2 [11] years) were analyzed with a mean (SD) follow-up period of 649 (181) days (1.8 [0.5] years). During 21 820 person-years of follow-up, 241 cases of ischemic stroke were reported. Risk factors associated with ischemic stroke after adjustment for oral anticoagulant use at enrollment were age (75-84 years: hazard ratio [HR], 1.74; 95% CI, 1.32-2.30; P < .001; and ≥85 years: HR, 2.41; 1.63-3.56; P < .001), hypertension (HR, 1.60; 95% CI, 1.15-2.23; P = .006), previous stroke (HR, 2.75; 95% CI, 2.09-3.62; P < .001), persistent or permanent AF (HR, 1.59; 95% CI, 1.21-2.10; P = .001), and body mass index less than 18.5 (HR, 1.55; 95% CI, 1.05-2.29; P = .03). Neither diabetes nor heart failure were identified as risk factors for ischemic stroke. Conclusions and Relevance: Previous stroke, advanced age, hypertension, persistent or permanent AF, and low body mass index were independent risk factors associated with ischemic stroke in Japanese patients with NVAF.