Background: The characteristics and clinical outcomes associated with sustained ventricular tachycardia and fibrillation (VT/VF) in Japanese acute myocardial infarction (AMI) patients remain unknown.

Methods and Results: Consecutive AMI patients (n=1,941) transferred to the Hirosaki University Hospital and treated with primary percutaneous coronary intervention (PCI) within 12 h of onset were retrospectively studied. The incidence of VT/VF during hospitalization was 8.3%, and 75% of cases occurred by the end of PCI. Independent predictors associated with VT/VF occurrence by the end of PCI and after PCI, respectively, were identified. Additionally, the differences between patients with VT and VF were examined, which revealed that the characteristics of patients and predictors for VT and VF were clearly different. Additionally, the QRS duration during VT was measured, which demonstrated the possible involvement of Purkinje fibers for VT in the acute phase of AMI. Of the patients with VT/VF, 12% required ECMO support due to refractory VT/VF despite intravenous antiarrhythmic agents such as β-blockers, amiodarone, and nifekalant. Among the patients discharged alive, 1,690 were followed up for a mean of 3.7 years. VT/VF occurrence during hospitalization did not affect the mid-term clinical outcomes even in patients with VT.

Conclusions: The results clearly indicated that VT/VF is still a serious complications of AMI. We need to identify patients at high risk of developing VT/VF for careful observation and appropriate intervention.

Background: Although right ventricular (RV) enlargement may affect RV diastolic dysfunction assessed by end-diastolic forward flow (EDFF) in patients with repaired tetralogy of Fallot (TOF), EDFF may also be modified by left ventricular (LV) hemodynamics. We hypothesized that EDFF is affected by LV hemodynamics, not limited to RV diastolic stiffening.

Methods and Results: Among 145 consecutive patients with repaired TOF who underwent catheterization, hemodynamic properties in 47 with consistent EDFF and 75 without EDFF were analyzed. Compared with patients without EDFF, those with EDFF had a large RV volume with a high regurgitant fraction. Although cardiac index and central venous pressure (CVP) were similar, contrast injection augmented CVP and LV end-diastolic pressure (EDP) in patients with vs. those without EDFF, suggesting compromised diastolic reserve. In patients with EDFF, the velocity–time integral (VTI) of EDFF was positively correlated with LVEDP and systemic vascular resistance, in addition to RV EDP. EDFF-VTI was correlated with hepatic venous wedge pressure and markers of hepatic dysfunction. Subanalysis of the older (≥6 years) half of the study cohort revealed that EDFF was associated with bi-atrial enlargement independent of RV volume, highlighting the pronounced role of EDFF on the diastolic property in the aged cohort.

Conclusions: EDFF-VTI in patients with repaired TOF reflects RV diastolic dysfunction, affected by the left heart system. EDFF-VTI indicates blood stagnation, which may be attributed to end-organ damage.

Background: This study assessed the prognostic importance of B-type natriuretic peptide (BNP) concentrations for clinical events after catheter ablation for atrial fibrillation (AF).

Methods and Results: We enrolled 1,750 consecutive patients undergoing initial AF ablation whose baseline BNP data were available from a large-scale multicenter observational cohort (TRANQUILIZE-AF Registry). The prognostic impact of BNP concentration on clinical outcomes, including recurrent tachyarrhythmias and a composite of heart failure (HF) hospitalization or cardiac death, was evaluated. Median baseline BNP was 94.2 pg/mL. During a median follow-up of 2.4 years, low BNP (<38.3 pg/mL) was associated with lower rates of recurrent atrial tachyarrhythmias than BNP concentrations ≥38.3 pg/mL (19.9% vs. 30.6% at 3 years; P<0.001) and HF (0.8% vs. 5.3% at 3 years; P<0.001). Multivariable Cox regression analyses revealed that low BNP was independently associated with lower risks of arrhythmia recurrence (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.47–0.82; P<0.001) and HF (HR 0.17; 95% CI 0.04–0.71; P=0.002). The favorable impact of low BNP on arrhythmia recurrence was prominent in patients with paroxysmal, but not non-paroxysmal, AF, particularly among those with long-standing AF.

Conclusions: Low BNP concentrations had a favorable impact on clinical outcomes after AF ablation. The heterogeneous impact of baseline BNP concentrations on arrhythmia recurrence for the subgroups of patients divided by AF type warrants future larger studies with longer follow-up periods.

Background: Atrial fibrillation (AF) is the most diagnosed arrhythmia in clinical settings. The fatty liver index (FLI) is a marker of liver steatosis with potential cardiovascular implications. This study investigated whether FLI could predict the risk of AF.

Methods and Results: We used data from the Suita Study, a Japanese population-based prospective cohort study. A total of 2,346 men and 3,543 women, aged 30–84 years, without prevalent AF were included and followed up. The diagnosis of AF was established during follow-up using electrocardiograms, hospital records, and death certificates. FLI was assessed during a baseline health checkup. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for incident AF per FLI quintile and log-transformed FLI. Within a median 14.5 years of follow-up, 142 men and 105 women developed AF. Compared with women in the third (middle) FLI quintile, women in the first (lowest), fourth, and fifth (highest) quintiles showed a higher risk of AF, with multivariable-adjusted HRs of 2.37 (95% CI 1.06–5.31), 2.60 (95% CI 1.30–5.17), and 2.04 (95% CI 1.00–4.18), respectively. No corresponding associations were observed in men. The change in log-transformed FLI was not associated with the risk of AF in either sex.

Conclusions: A U-shaped association between FLI and AF risk was detected in Japanese women. FLI could be a screening tool to detect women at high risk of developing AF.

Background: Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing percutaneous coronary intervention (PCI).

Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1–3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 [≤5 medications] 12.5%, T2 [6–7] 16.5%, and T3 [≥8] 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.08–1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12–1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 [95% CI 0.83–1.09; P=0.47] and HR 1.06 [95% CI 0.91–1.23; P=0.48], respectively).

Conclusions: In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.

Background: Early intervention in prehospital settings is important for treating patients with acute coronary syndrome (ACS). Emergency medical technicians (EMTs) are the essential first responders who treat these patients, and their current attitudes towards electrocardiograms (ECGs) have not been identified. This study investigated the awareness of EMTs of ECGs to shorten hospital arrival time, improving patient prognosis.

Methods and Results: An anonymous questionnaire survey, with 27 statements about ECG and ACS response, was administered to 395 EMTs. The statements were related to interest, motivation, learning status, confidence, and norms pertaining to ECGs, a sense of perceived behavioral control, and training courses. The primary outcome was the perception of EMTs that their interpretation of an ECG affected patient prognosis (Statement [S] 1). Participants assigned scores for each statement using a scale ranging from 1 (strongly disagree) to 10 (strongly agree). The mean score for S1 was 7.09. Mean scores for statements regarding confidence and learning status were 3.96 and 3.53, respectively. The participants had a positive impression of training courses (score >5.5).

Conclusions: The EMTs experience was that their interpretation of an ECG could affect the prognosis of patients with ACS. Conversely, they lacked confidence reading ECGs, but were willing to attend ECG training courses. Therefore, efficient training programs need to be established to achieve a better prognosis for ACS patients.

Background: Acute aortic dissection (AAD) has high morbidity and a high fatality rate for a cardiovascular disease. Recent studies suggested that the incidence of AAD is increasing. However, the actual incidence and mortality rates of AAD are not well known. This study investigated the current epidemiology of AAD within the Yatsushiro medical jurisdictional area.

Methods and Results: A population-based review of patients with AAD was performed in a geographically well-defined area. Data were collected retrospectively from January 2011 to December 2020 for a total of 196 patients with AAD (Stanford Type A, n=126 [64.3%]; Stanford Type B, n=70 [35.7%]). The mean patient age was 74.3 years, and 55.6% (109/196) were women. The crude and age-standardized incidence rates of AAD in our medical jurisdictional area were 13.6 and 11.4 per 100,000 inhabitants per year, respectively. The crude and age-standardized 30-day mortality rates of AAD were 4.9 and 4.0 per 100,000 inhabitants per year, respectively. There were upward tendencies for both the incidence and 30-day mortality rate of AAD with age, with both being significantly higher in patients aged ≥85 years (P<0.001).

Conclusions: This population-based study detected a higher incidence of AAD than previous studies, but reported a lower incidence of AAD in men than in women. Increasing age was associated with an increased incidence and mortality rate of AAD.

Background: Microvascular reperfusion following percutaneous coronary intervention (PCI) is associated with the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We investigated how plaque characteristics detected by optical coherence tomography (OCT) in STEMI patients affect the status of the microcirculation during PCI.

Methods and Results: This retrospective, single-center study was a post hoc analysis basedon the multicenter SALVAGE randomized control trial (NCT03581513) that enrolled 629 STEMI patients, and finally we enrolled 235 patients who underwent PCI and pre-intervention OCT. Microvascular perfusion was evaluated using the Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion frame count (TMPFC). Patients were divided into 3 groups based on the change in TMPFC from before to after PCI: improving TMPFC (n=11; 4.7%), stable TMPFC (n=182; 77.4%), and worsening TMPFC group (n=42; 17.9%). The proportion of patients with a microcirculation dysfunction before reperfusion was 11.9%, which increased significantly by (P=0.079) 8.5% to 20.4% after reperfusion. Compared with plaque characteristics in the stable and worsening TMPFC groups, the improving TMPFC group had fewer thrombi (90.7% and 90.5% vs. 89.4%, respectively; P=0.018), a lower proportion of plaque rupture (66.5% and 66.3% vs. 54.5%, respectively; P=0.029), and a lower proportion of lipid-rich plaques (89.6% and 88.1% vs. 63.6%, respectively; P=0.036).

Conclusions: PCI may not always achieve complete myocardial reperfusion. Thrombi, plaque rupture, and lipid-rich plaques detected by OCT can indicate microcirculation dysfunction during the reperfusion period.

Background: Little is known about clinical or sociodemographic factors that influence health-related quality of life (HRQoL) in patients with adult congenital heart disease (ACHD).

Methods and Results: We conducted a nationwide prospective cross-sectional multicenter study at 4 large ACHD centers in Japan. From November 2016 to June 2018, we enrolled 1,223 ACHD patients; 1,025 patients had an HRQoL score. Patients completed a questionnaire survey, including sociodemographic characteristics, and the 36-Item Short-Form Health Survey (SF-36). To determine factors associated with HRQoL, correlations between 2 SF-36 summary scores (i.e., physical component score [PCS] and mental component score [MCS]) and other clinical or sociodemographic variables were examined using linear regression analysis. In multivariable analysis, poorer PCS was significantly associated with 11 variables, including older age, higher New York Heart Association class, previous cerebral infarction, being unemployed, and limited participation in physical education classes and sports clubs. Poorer MCS was associated with congenital heart disease of great complexity, being part of a non-sports club, current smoking, and social drinking. Student status and a higher number of family members were positively correlated with MCS.

Conclusions: This study demonstrates that HRQoL in ACHD patients is associated with various clinical and sociodemographic factors. Further studies are needed to clarify whether some of these factors could be targets for future intervention programs to improve HRQoL outcomes.

Background: The relationships between preoperative fractional flow reserve (FFR) values of the left anterior descending artery (LAD), FFR_LAD, and intraoperative transit time flow measurement (TTFM) variables in coronary artery bypass grafting (CABG) remain unclear.

Methods and Results: We retrospectively collected data for 74 in situ left internal thoracic artery (LITA) grafts and 27 saphenous vein grafts (SVGs) to the LAD that were shown to be patent on postoperative angiography. Spearman correlation coefficients were determined between FFR_LADand TTFM parameters of the LITA graft, as follows: maximum flow (Q_max), −0.22 (P=0.077); minimum flow (Q_min), −0.40 (P=0.014); mean flow (Q_m), −0.35 (P=0.039); pulsatility index (PI), 0.33 (P=0.008); diastolic filling (DF): 0.01 (P=0.83); and systolic reverse flow (SRF), 0.37 (P=0.002). Spearman correlation coefficients between FFR_LADand TTFM parameters of the SVG to LAD were: Q_max, −0.65 (P=0.004); Q_min, −0.43 (P=0.044); Q_m, −0.75 (P=0.001); PI, 0.53 (P=0.033); DF, 0.14 (P=0.48); and SRF, 0.61 (P=0.009).

Conclusions: Both LITA grafts and SVGs to the LAD show negative correlations for FFR_LADwith Q_minand Q_m, but positive correlations for FFR_LADwith PI and SFR. These relationships between FFR_LADand TTFM variables of CABG grafts to the LAD should be recognized.

Background: In Taiwan, infective native aortic aneurysms (INAAs) are relatively common, so the aim of present study was to demonstrate the comparative outcomes of endovascular repair for thoracic and abdominal INAAs.

Methods and Results: Patients with naïve thoracic or abdominal INAAs managed with endovascular repair between 2001 and 2018 were included in this multicenter retrospective cohort. The confounding factors were adjusted with propensity score (PS). Of the 39 thoracic and 43 abdominal INAA cases, 41 (50%) presented with aneurysmal rupture, most of which were at the infrarenal abdominal (n=35, 42.7%) or descending thoracic aorta (n=25, 30.5%). Salmonella spp. was the most frequently isolated pathogen. The overall in-hospital mortality rate was 18.3%. The risks of in-hospital death and death due to rupture were significantly lower with thoracic INAAs (12.8% vs. 23.3%; PS-adjusted odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06–0.96; 0.1% vs. 9.3%; PS-adjusted OR 0.11, 95% CI 0.01–0.90). During a mean follow-up of 2.5 years, the risk of all-cause death was significantly higher with thoracic INAAs (35.3% vs. 15.2%; PS-adjusted HR 6.90, 95% CI 1.69–28.19). Chronic kidney disease (CKD) was associated with death.

Conclusions: Compared with thoracic INAAs, endovascular repair of abdominal INAAs was associated with a significantly higher in-hospital mortality rate. However, long-term outcomes were worse for thoracic INAAs, with CKD and infections being the most important predictor and cause of death, respectively.

Background: The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan.

Methods and Results: This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2–4 and sustained to Month 12.

Conclusions: Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.

Background: Hyogo Prefecture has managed smoking ban legislation with partial restrictions in public places (Hyogo-L) since 2013. Previous studies have reported a significant decrease in admissions for acute coronary syndrome (ACS) in Kobe-city, but not in other districts of Hyogo Prefecture in the 2 years after Hyogo-L. The aim of the present study was to define the long-term effect of Hyogo-L.

Methods and Results: The JROAD-DPC dataset was used to collect information on the number of hospitalizations for ACS in Hyogo Prefecture, and in Osaka-city without smoking ban legislation, from April 2013 to March 2020. Poisson regression analysis was performed to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). ACS records of 3,101 in Kobe-city, 11,375 in areas of Hyogo Prefecture other than Kobe-city and 11,079 in Osaka-city were collected for admissions. The incidence of ACS reduced significantly over time in Kobe-city [IRR (95% CI); 0.96 (0.94–0.97)], but did not reduce in the others. The decrease in Kobe-city was observed in ACS patients without smoking, hypertension, and hyperlipidemia, but not in those with such risk factors.

Conclusions: The long-term ACS reduction or non-reduction under Hyogo-L was determined at the initial period and the same scenario continued, supporting the importance of legislation and compliance with the smoking ban. The lowering effect was remarkable in ACS patients without risk factors such as non-smoking.

Background: We have reported that a prehospital 12-lead electrocardiography system (P-ECG) contributed to transport of suspected acute coronary syndrome (ACS) patients to appropriate institutes and in this study, we compared its usefulness between urban and rural areas, and between weekday daytime and weekday nighttime/holiday.

Methods and Results: Consecutive STEMI patients who underwent successful primary percutaneous coronary intervention after using P-ECG were assigned to the P-ECG group (n=123; 29 female, 70±13 years), and comparable STEMI patients without using P-ECG were assigned to the conventional group (n=117; 33 females, mean age 70±13 years). There was no significant difference in door-to-reperfusion times between the rural and urban cases (70±32 vs. 69±29 min, P=0.73). Door-to-reperfusion times in the urban P-ECG group were shorter than those in the urban conventional group for weekday nighttime/holiday (65±21 vs. 83±32 min, P=0.0005). However, there was no significance different between groups for weekday daytime. First medical contact to reperfusion time (90±22 vs. 105±37 min, P=0.0091) in the urban P-ECG group were significantly shorter than in the urban conventional groups for weekday nighttime/holiday, but were not significantly different between the groups for weekday daytime.

Conclusions: P-ECG is useful even in urban areas, especially for patients who develop STEMI during weekday nighttime or while on a holiday.

Background: Extracellular volume fraction (ECV) on magnetic resonance imaging can predict prognosis after aortic valve replacement in patients with aortic stenosis (AS). However, the usefulness of ECV on computed tomography (CT) for patients who have undergone transcatheter aortic valve replacement (TAVR) is unclear, so we investigated whether ECV analysis on CT is associated with clinical outcomes in TAVR candidates.

Methods and Results: We analyzed 127 patients with severe AS who underwent preoperative CT for TAVR. We evaluated the utility of ECV analysis on single-energy CT for predicting patient prognosis after TAVR. The primary outcome was a composite of all-cause death and hospitalization due to heart failure (HF) after TAVR. 15 patients (12%) had composite outcomes: 4 deaths and 11 hospitalizations due to HF. In multivariate survival analysis using the Cox proportional hazard model, atrial fibrillation (AF) (hazard ratio (HR), 7.86; 95% confidence interval (CI), 2.57–24.03; P<0.001), history of congestive HF (HR, 4.91; 95% CI, 1.49–16.2; P=0.009) and ECV ≥32.6% on CT (HR, 6.96; 95% CI, 1.92–25.12; P=0.003) were independent predictors of composite outcomes. On Kaplan-Meier analysis, the higher ECV group (≥32.6%) had a significantly greater number of composite outcomes than the lower ECV group (P<0.001).

Conclusions: ECV on CT is an independent predictor of prognosis after TAVR.

Background: The HELT-E₂S₂score, which assigns 1 point to Hypertension, Elderly aged 75–84 years, Low body mass index <18.5 kg/m², and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.

Methods and Results: We evaluated the prognostic performance of the HELT-E₂S₂score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E₂S₂score was 0.661 (95% confidence interval [CI], 0.629–0.692), which was numerically higher than with the CHADS₂score (0.644, 95% CI 0.613–0.675; P=0.15 vs. HELT-E₂S₂) or CHA₂DS₂-VASc score (0.650, 95% CI, 0.619–0.680; P=0.37 vs. HELT-E₂S₂). In the SAKURA AF Registry, the C-statistic of the HELT-E₂S₂score was consistently higher than the CHADS₂and CHA₂DS₂-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals.

Conclusions: The HELT-E₂S₂score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS₂or CHA₂DS₂-VASc scores may vary across different hospital settings.

Background: Hyperpolypharmacy is associated with adverse outcomes in older adults, but because literature on its association with cardiovascular (CV) outcomes after acute decompensated heart failure (ADHF) is sparse, we investigated the relationships among hyperpolypharmacy, medication class, and death in patients with HF.

Methods and Results: We evaluated the total number of medications prescribed to 884 patients at discharge following ADHF. Patients were categorized into nonpolypharmacy (<5 medications), polypharmacy (5–9 medications), and hyperpolypharmacy (≥10 medications) groups. We examined the relationship of polypharmacy status with the 2-year mortality rate. The proportion of patients taking ≥5 medications was 91.3% (polypharmacy, 55.3%; hyperpolypharmacy, 36.0%). Patients in the hyperpolypharmacy group showed worse outcomes than patients in the other 2 groups (P=0.002). After multivariable adjustment, the total number of medications was significantly associated with an increased risk of death (hazard ratio [HR] per additional increase in the number of medications, 1.05; 95% confidence interval [CI], 1.01–1.10; P=0.027). Although the number of non-CV medications was significantly associated with death (HR, 1.07; 95% CI, 1.02–1.13; P=0.01), the number of CV medications was not (HR, 1.01; 95% CI, 0.92–1.10; P=0.95).

Conclusions: Hyperpolypharmacy due to non-CV medications was associated with an elevated risk of death in patients after ADHF, suggesting the importance of a regular review of the prescribed drugs including non-CV medications.

Background: Acute limb ischemia (ALI) is a limb- and life-threatening condition and urgent treatment including revascularization should be offered to patients unless the limb is irreversibly ischemic. The aim of this study was to investigate 1-year clinical outcomes and prognostic factors following revascularization in patients with ALI.

Methods and Results: A retrospective, multicenter, nonrandomized study examined 185 consecutive patients with ALI treated by surgical revascularization (SR), endovascular revascularization (ER), or hybrid revascularization (HR) in 6 Japanese medical centers from January 2015 to August 2021. The 1-year amputation-free survival (AFS) rate was estimated to be 69.2% (95% confidence interval [CI], 62.8–76.2%). There were no significant differences among SR, ER, and HR regarding both technical success and perioperative complications. Multivariate analysis revealed that Rutherford category IIb and III ischemia (hazard ratio [HR]: 1.86; 95% CI: 1.06–3.25), supra- to infrapopliteal lesion (HR: 2.06; 95% CI: 1.08–3.95), and technical failure (HR: 2.58; 95% CI: 1.49–4.46) were independent risk factors for 1-year AFS.

Conclusions: Rutherford category IIb and III ischemia, supra- to infrapopliteal lesions, and technical failures were identified as independent risk factors for 1-year AFS. Furthermore, patients with multiple risk factors had a lower AFS rate.

Background: Pulsed field ablation (PFA) is a non-thermal energy source with promising safety and efficacy advantages. We aimed to develop a convenient, safe, effective and fast method of pulmonary vein isolation (PVI) utilizing a penta-spline PFA catheter via a single femoral vein and a venous closure system.

Methods and Results: Consecutive patients (n=50; mean age: 63.6±10.7 years, 38% female) presenting with AF (paroxysmal AF: 56%) underwent first-time PVI via PFA. A single ultrasound-guided femoral vein puncture and a single transseptal puncture were used. After PVI using the penta-spline PFA catheter, extra pulse trains were added to the posterior wall for wide antral circumferential ablation. A venous closure system was used and a Donati suture was performed. The pressure bandage was removed after 1 h. A total of 196 PVs were identified and isolated with PFA only. The mean procedural time was 27.4±6.6 min, and the mean dwelling time was 14.4±5.5 min. Time to ambulation was 3.3±3.1 h. No severe complications occurred. During a mean follow-up of 6.5±2.1 months, 41/50 patients (82%) remained in sinus rhythm.

Conclusions: The combination of a single venous puncture, single transseptal puncture approach using PFA and vascular closure device resulted in a 100% rate of acute PVI and an extraordinarily fast procedure and time to ambulation. The rate of periprocedural complications was low.

Background: The Micra leadless pacemaker has demonstrated favorable outcomes in global trials, but its real-world performance and safety in a Japan-specific population is unknown.

Methods and Results: Micra Acute Performance (MAP) Japan enrolled 300 patients undergoing Micra VR leadless pacemaker implantation in 15 centers. The primary endpoint was the acute (30-day) major complication rate. The 30-day and 6-month major complication rates were compared to global Micra studies. All patients underwent successful implantation with an average follow-up of 7.23±2.83 months. Compared with previous Micra studies, Japanese patients were older, smaller, more frequently female, and had a higher pericardial effusion risk score. 11 acute major complications were reported in 10 patients for an acute complication rate of 3.33% (95% confidence interval: 1.61–6.04%), which was in line with global Micra trials. Pericardial effusion occurred in 4 patients (1.33%; 3 major, 1 minor). No procedure or device-related deaths occurred. Frailty significantly improved from baseline to follow-up as assessed by Japan Cardiovascular Health Study criteria.

Conclusions: In a Japanese cohort, implantation of the Micra leadless pacemaker had a high success rate and low major complication rate. Despite the Japan cohort being older, smaller, and at higher risk, the safety and performance was in line with global Micra trials.

Background: It remains unclear which comorbidities, other than lipid parameters, or combination of comorbidities, best predicts cardiovascular events in patients with known coronary artery disease (CAD) treated with statins. Therefore, we aimed to identify the nonlipid-related prognostic factors and risk stratification of patients with stable CAD enrolled in the REAL-CAD study.

Methods and Results: Blood pressure, glucose level, and renal function were considered as risk factors in the 11,141 enrolled patients. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina. The secondary composite endpoint was the primary endpoint and/or coronary revascularization. A significantly worse prognosis at the primary endpoint was observed in the estimated glomerular filtration rate (eGFR) ≤60 group, and the combination of eGFR ≤60 and HbA1c ≥6.0 was the worst (hazard ratio (HR) 1.66; P<0.001). However, even in the eGFR >60 group, systolic blood pressure (SBP) ≥140 mmHg met the secondary endpoint (HR 1.33; P=0.006), and the combination of eGFR ≤60 and HbA1c ≥6.0 was also the worst at the secondary endpoint (HR 1.35; P=0.002).

Conclusions: Regarding nonlipid prognostic factors contributing to the incidence of cardiovascular events in statin-treated CAD patients, renal dysfunction was the most significant, followed by poor glucose control and high SBP.

Background: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.

Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death.

Conclusions: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

Background: Renal congestion is a potential prognostic factor in patients with heart failure and recently, assessment has become possible with intrarenal Doppler ultrasonography (IRD). The association between renal congestion assessed by IRD and outcomes after mitral transcatheter edge-to-edge repair (TEER) is unknown, so we aimed to clarify renal congestion and its prognostic implications in patients with mitral regurgitation (MR) who underwent TEER using MitraClip system.

Methods and Results: Patients with secondary MR who underwent TEER and were assessed for intrarenal venous flow (IRVF) by IRD were classified according to their IRVF pattern as continuous or discontinuous. Of the 105 patients included, 78 patients (74%) formed the continuous group and 27 (26%) were the discontinuous group. Kaplan-Meier analysis revealed significant prognostic power of the IRVF pattern for predicting the composite outcome of all-cause death and heart failure rehospitalization (log-rank P=0.0257). On multivariate Cox regression analysis, the composite endpoint was independently associated with the discontinuous IRVF pattern (hazard ratio, 3.240; 95% confidence interval, 1.300–8.076; P=0.012) adjusted using inverse probability of treatment weighting.

Conclusions: IRVF patterns strongly correlated with clinical outcomes without changes in renal function. Thus, they may be useful for risk stratification after mitral TEER for patients with secondary MR.

Evidence indicates a role of cellular senescence and systemic insulin resistance (hyperinsulinemia) in the pathogenesis of age-related cardiovascular–metabolic disorders, including heart failure, atherosclerotic diseases, obesity, and diabetes. “Metabolic remodeling” is one of the keywords for aging research, and studies with brown adipose tissue have shown that maintaining the homeostasis of this organ is crucial to suppressing the progression of pathologies in obesity and heart failure. The mechanisms contributing to the synchronization of aging (sync-aging) are mysterious and interesting. “Senometabolite” or “senoprotein” are defined as circulating molecules that have causal roles in sync-aging, which requires the establishment of new concepts: age-related fibrotic disorders (A-FiDs), and senometabolite-related disorders (SRDs). Globally, researchers are active in comprehensive and conclusive studies targeting age-related circulating molecules. Recently, the senolytic approach opened a new avenue for aging research. Senolysis, mediated through a genetic/pharmacologic/vaccination approach, reversed aging and pathologies in age-related diseases. Suppression of prosenescent molecules (senocules) and senolysis, the specific depletion of senescent cells, will become next-generation therapies for cardiovascular diseases.

Background: Acute decompensated heart failure (ADHF) has a poor prognosis and common comorbidities may be contributory. However, evidence for the association between dementia and clinical outcomes in patients with is sparse and it requires further investigation into risk reduction.

Methods and Results: We assessed the clinical profiles and outcomes of 1,026 patients (mean age 77.8 years, 43.2% female) with ADHF enrolled in the CURE-HF registry to evaluate the relationship between investigator-reported dementia status and clinical outcomes (all-cause death, cardiovascular (CV) death, non-CV death, and HF hospitalization) over a median follow-up of 2.7 years. In total, dementia was present in 118 (11.5%) patients, who experienced more drug interruptions and HF admissions due to infection than those without dementia (23.8% vs. 13.1%, P<0.01; 11.0% vs. 6.0%, P<0.01, respectively). Kaplan-Meier analysis revealed that dementia patients had higher mortality rates than those without dementia (log-rank P<0.001). After multivariable adjustment for demographics and comorbidities, dementia was significantly associated with an increased risk of death (adjusted hazard ratio, 1.43; 95% confidence interval, 1.06–1.93, P=0.02) and non-CV death (adjusted hazard ratio, 1.65; 95% confidence interval, 1.04–2.62, P=0.03), but no significant associations between dementia and CV death or HF hospitalization were observed (both, P>0.1).

Conclusions: In ADHF patients dementia was associated with aggravating factors for HF admission and elevated risk of death, primarily non-CV death.

Background: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.

Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058–1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449–0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20–30 s.

Conclusions: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients’ professional lives. Smoking history worsens patients’ condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

Background: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.

Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5–2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer.

Conclusions: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Background: In patients with atrial fibrillation (AF) and severe blood stasis in the left atrial appendage (LAA), dense spontaneous echo contrast (SEC) disturbs the distinct visualization of the LAA interior, thus making thrombus diagnosis inconclusive. We aimed to prospectively assess the efficacy and safety of a protocol for a low-dose isoproterenol (ISP) infusion to reduce SEC to exclude an LAA thrombus.

Methods and Results: We enrolled 17 patients with AF and dense SEC (Grade 4 or sludge). ISP was infused with gradually increasing doses of 0.01, 0.02, and 0.03 μg/kg/min at 3-min intervals. After increasing the dose to 0.03 μg/kg/min for 3 min, or when the LAA interior was visible, the infusion was terminated. We reassessed the SEC grade, presence of an LAA thrombus, LAA function, and left ventricular ejection fraction (LVEF) within 1 min of ISP termination. Compared with baseline, ISP significantly increased LAA flow velocity, the LAA emptying fraction, LAA wall velocities, and LVEF (all P<0.01). ISP administration significantly reduced the SEC grade (median) from 4 to 1 (P<0.001). The SEC grade decreased to ≤2 in 15 (88%) patients, and the LAA thrombus was excluded. There were no adverse events.

Conclusions: Low-dose ISP infusion may be effective and safe to reduce SEC and exclude an LAA thrombus by improving LAA function and LVEF.

Background: Previous studies have suggested a relationship between type A personality and the occurrence of coronary artery disease, so we used intravascular optical coherence tomography (OCT) to investigate the morphological characteristics of culprit plaques in acute myocardial infarction (AMI) patients with different scores of type A personality.

Methods and Results: A total of 221 AMI patients who underwent preintervention imaging of culprit lesions and an assessment of type A behavior pattern were included. According to the scores for the behavior questionnaire, these patients were divided into 3 groups: non-type A personality (n=91), intermediate personality (n=73), and type A personality (n=57). Patients with type A personality were younger (P=0.003) and had a higher level of total cholesterol (P=0.029) and more severe luminal stenosis (P=0.046). In addition, the prevalence of microchannels (P<0.001), macrophage accumulation (P<0.001), and plaque rupture (P=0.010) with greater number (P<0.001), cavity angle (P<0.001), and length (P<0.001) was highest in the type A personality group.

Conclusions: The culprit lesions of AMI patients with increased scores for type A personality had more severe coronary luminal stenosis, and the proportion of vulnerable features was increased.

Background: Cardiac calmodulinopathy, characterized by a life-threatening arrhythmia and sudden death in the young, is extremely rare and caused by genes encoding calmodulin, namely calmodulin 1 (CALM1), CALM2, and CALM3.

Methods and Results: We screened 195 symptomatic children (age 0–12 years) who were suspected of inherited arrhythmias for 48 candidate genes, using a next-generation sequencer. Ten probands were identified as carrying variants in any of CALM1–3 (5%; median age 5 years), who were initially diagnosed with long QT syndrome (LQTS; n=5), catecholaminergic polymorphic ventricular tachycardia (CPVT; n=3), and overlap syndrome (n=2). Two probands harbored a CALM1 variant and 8 probands harbored 6 CALM2 variants. There were 4 clinical phenotypes: (1) documented lethal arrhythmic events (LAEs): 4 carriers of N98S in CALM1 or CALM2; (2) suspected LAEs: CALM2 p.D96G and D132G carriers experienced syncope and transient cardiopulmonary arrest under emotional stimulation; (3) critical cardiac complication: CALM2 p.D96V and p.E141K carriers showed severe cardiac dysfunction with QTc prolongation; and (4) neurological and developmental disorders: 2 carriers of CALM2 p.E46K showed cardiac phenotypes of CPVT. Beta-blocker therapy was effective in all cases except cardiac dysfunction, especially in combination with flecainide (CPVT-like phenotype) and mexiletine (LQTS-like).

Conclusions: Calmodulinopathy patients presented severe cardiac features, and their onset of LAEs was earlier in life, requiring diagnosis and treatment at the earliest age possible.

Background: There are limited data about predictors of atrial fibrillation (AF) recurrence after totally thoracoscopic ablation (TTA). This study investigated the clinical implication of left atrial appendage emptying velocity (LAAV) in patients undergoing TTA.

Methods and Results: Patients who underwent TTA between 2012 and 2015 at a tertiary hospital were prospectively enrolled in this study. LAAV was measured and averaged over five heart beats from preoperative transesophageal echocardiography. The primary outcome was a freedom from recurrent AF or atrial flutter (AFL) detected on 24-h Holter monitoring or an electrocardiogram over a 3-year period after TTA. In all, 129 patients were eligible for analysis in this study. The mean (±SD) patient age was 54.4±8.8 years, and 95.3% were male. During the 3 years after TTA, the overall event-free survival rate was 65.3%. LAAV was an independent predictor of recurrent AF/AFL during the 3-year period after TTA (per 1-cm/s increase, adjusted hazard ratio [aHR] 0.95; 95% confidence interval [CI] 0.91–0.99; P=0.016). Event-free survival was significantly lower among patients with a low LAAV (<20 cm/s; n=21) compared with those with a normal (≥40 cm/s; n=38; aHR 6.11; 95% CI 1.42–26.15; P=0.015) or intermediate (LAAV ≥20 and <40 cm/s; n=70; aHR 2.74, 95% CI 1.29–5.83; P=0.009) LAAV.

Conclusions: In patients with AF, LAAV was significantly associated with the risk of long-term recurrence of AF after TTA.

Background: Antithrombotic therapy after left atrial appendage closure (LAAC) in patients at high risk of bleeding remains controversial. We present real-world clinical outcomes of LAAC.

Methods and Results: Data from 74 consecutive patients who received LAAC therapy between January 2020 and June 2022 were analyzed. Patients received 1 of 3 antithrombotic therapies according to the bleeding risk category or clinical event. Regimen 1 was based on a prior study, regimen 2 comprised a lower antiplatelet drug dose without dual antiplatelet therapy, and regimen 3 was antiplatelet drug administration for as long as possible to patients with uncontrollable bleeding who were required to stop anticoagulant drugs. Overall, 73 (98.6%) procedures were successful. Of them, 16 (21.9%) patients were selected for regimen 1, 46 (63.0%) for regimen 2, and 11 (15.1%) for regimen 3. Device-related thrombosis (13% vs. 0% vs. 0%, P=0.0257) only occurred with regimen 1. There was no difference in major bleeding event rates (6% vs. 2% vs. 9%, P=0.53).

Conclusions: The post-LAAC antithrombotic regimen was modified without major concerns.

Background: Pulmonary vein stenosis (PVS) after PV isolation (PVI) for atrial fibrillation (AF) is a severe complication that requires angioplasty. This study aimed to compare the reduction of the cross-sectional PV area (PVA) and the incidence of PVS after cryoballoon (CB)-PVI, hot balloon (HB)-PVI, or laser balloon (LB)-PVI.

Methods and Results: A total of 320 patients who underwent an initial catheter ablation procedure for AF using a CB, HB, or LB in 2 hospitals were included. They underwent contrast-enhanced multidetector CT before and 3 months after the procedure. In all 4 PVs, the reduction in PVA was more significant in the LB group than in the CB or HB groups, respectively. Moderate (50–75%) and severe (>75%) PVS were observed in 5.3% and 0.5% of the PVs, respectively. Although moderate PVS was more frequently observed in the LB group than in the CB or HB groups (8.2%, 3.8%, and 5.0%; P=0.03), the incidence of severe PVS was similar in the LB, CB, and HB groups (0.3%, 0.5%, and 1.0%; P=0.46). Symptomatic PVS requiring intervention occurred in 1 (0.3%) patient.

Conclusions: Although the reduction in cross-sectional PVA and the incidence of moderate PVS after LB-PVI was more significant than after CB-PVI or HB-PVI, it rarely led to severe PVS. Symptomatic PVS requiring intervention was rare after the balloon ablation of AF.

Background: Grafting the right gastroepiploic artery (GEA) to the right coronary artery (RCA) is effective, but preoperative evaluation of arterial conduit availability has not been established. By comparing the midterm graft results, we aimed to assess the efficacy of preoperative evaluation of the GEA using computed tomography (CT).

Methods and Results: We retrospectively examined patients who underwent isolated coronary artery bypass grafting surgery between April 2010 and December 2020, and those whose GEA was grafted to the RCA were selected: 55 patients were included in the study analysis. Postoperative evaluations were performed during the early phase, 1 year postoperatively, and at follow-up evaluations. The outer diameter of the proximal GEA was compared with the midterm graft patency grade on CT and patients were classified as Functional (Grade A) or Dysfunctional (Grades O or B). The proximal GEA outer diameters were significantly different between the Functional and Dysfunctional groups (P<0.001). Furthermore, multivariate Cox regression analysis revealed that this diameter was an independent predictor of graft functionality (P<0.001). Patients with outer proximal diameters larger than the cutoff value had superior graft results at 3 years postoperatively. The rate of freedom from a dysfunctional graft at 3 years postoperatively was 95.5% and 45.5% for the Larger and Smaller diameter subgroups, respectively (P<0.001).

Conclusions: Preoperative evaluation of the outer diameter of the proximal GEA, excluding calcified GEA, using CT is a minimally invasive and useful method, and may improve midterm results of in-situ GEA grafting, even in severe stenotic lesions.

Background: There is a scarcity of data evaluating contemporary real-world dual antiplatelet therapy (DAPT) strategies after percutaneous coronary intervention (PCI).

Methods and Results: In the OPTIVUS-Complex PCI study multivessel cohort enrolling 982 patients undergoing multivessel PCI, including left anterior descending coronary artery using intravascular ultrasound (IVUS), we conducted 90-day landmark analyses to compare shorter and longer DAPT. DAPT discontinuation was defined as withdrawal of P2Y₁₂inhibitors or aspirin for at least 2 months. The prevalence of acute coronary syndrome and high bleeding risk by the Bleeding Academic Research Consortium were 14.2% and 52.5%, respectively. The cumulative incidence of DAPT discontinuation was 22.6% at 90 days, and 68.8% at 1 year. In the 90-day landmark analyses, there were no differences in the incidences of a composite of death, myocardial infarction, stroke, or any coronary revascularization (5.9% vs. 9.2%, log-rank P=0.12; adjusted hazard ratio, 0.59; 95% confidence interval, 0.32–1.08; P=0.09) and BARC type 3 or 5 bleeding (1.4% vs. 1.9%, log-rank P=0.62) between the off- and on-DAPT groups at 90 days.

Conclusions: The adoption of short DAPT duration was still low in this trial conducted after the release of the STOPDAPT-2 trial results. The 1-year incidence of cardiovascular events was not different between the shorter and longer DAPT groups, suggesting no apparent benefit of prolonged DAPT in reducing cardiovascular events even in patients who undergo multivessel PCI.