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The Japan Circulation Society launched the STOP-MI campaign in 2014, focusing on immediate hospital arrival for acute myocardial infarction (AMI) treatment. This study aimed to determine the factors influencing longer prehospital time among patients with AMI in Japan.Methods and Results:This study analyzed a total of 4,625 AMI patients enrolled in the Osaka Acute Coronary Insufficiency Study registry from 1998 to 2014. The prehospital time delay was defined as the time interval from the onset of initial symptoms to hospital arrival time ≥2 h. Among eligible patients, 2,927 (63.3%) had a prehospital time ≥2 h. In multivariable analyses, age 65-79 years (adjusted odds ratio [AOR] 1.19, 95% confidence interval [CI] 1.02-1.39), age ≥80 years (AOR 1.42, 95% CI 1.13-1.79), diabetes mellitus (AOR 1.33, 95% CI 1.16-1.52), and onset time of 0:00-5:59 h (AOR 1.63, 95% CI 1.37-1.95) were positively associated with prehospital time ≥2 h, whereas smoking (AOR 0.78, 95% CI 0.68-0.90) and ambulance use (AOR 0.37, 95% CI 0.32-0.43) were negatively associated with prehospital time ≥2 h.Older age, diabetes mellitus, and nighttime onset were associated with prehospital time delay for AMI patients, whereas smoking and ambulance use were associated with no prehospital time delay. Healthcare providers and patients could help reduce the time to get to a medical facility by being aware of these findings.

The prognostic significance of combining intra-aortic balloon pumping (IABP) with extracorporeal membrane oxygenation (ECMO) for acute myocardial infarction (AMI) patients is still unclear. We investigated whether combining IABP with veno-arterial (VA)-ECMO is associated with a lower risk of short-term mortality.Among 12,093 AMI cases enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS), we identified 519 who were administered VA-ECMO during hospitalization. Among these, 459 received IABP support (IABP group) and 60 cases did not (no-IABP group). The primary endpoint was 30-day all-cause death; the secondary endpoint was major bleeding. Logistic regression analysis using original data was conducted. We also established weighted logistic regression models with inverse probability of treatment weighting (IPTW).Logistic regression analysis revealed that IABP use was significantly associated with a reduced risk of 30-day death in the original data [odds ratio (OR) 0.504, 95% confidence interval (CI) 0.282-0.901, p = 0.021]. After IPTW-adjustment for clinically relevant covariates with the use of IABP, patients receiving VA-ECMO with IABP had a lower risk of 30-day death (OR 0.816, 95% CI 0.746-0.892, p0.001) compared to those without IABP. The incidence of major bleeding was comparable between the groups (IABP 29.0% vs. non-IABP 21.7%, p=0.302). However, the risk of major bleeding was higher in the IABP group after IPTW-adjustment (OR 1.092, 95% CI 1.008-1.184, p=0.032).IABP support for AMI patients with VA-ECMO was significantly associated with reduced risk of short-term mortality, suggesting that the addition of IABP support might contribute to improved survival in AMI patients requiring VA-ECMO.

Background Extensive ablation in addition to pulmonary vein isolation (PVI) would be effective for modification of non-pulmonary vein (non-PV) substrates, whereas PVI might be sufficient for elimination of PV triggers. This study aimed to test the hypothesis that in patients with reproducible atrial fibrillation (AF) triggered by premature atrial contractions originating only from PVs, PVI alone can be sufficient to maintain sinus rhythm.Methods and Results:This study is a prespecified subanalysis of the EARNEST-PVI randomized controlled trial. This study investigated the efficacy of the PVI-alone strategy (PVI-alone) in comparison with the extensive strategy (PVI-plus) for persistent AF with a trigger-based mechanism vs. a substrate-based mechanism. Patients were stratified into 3 groups based on AF mechanisms: (1) Substrate group (N=236); (2) PV trigger group (N=236); and (3) non-PV trigger group (N=24). The hazard ratios for AF recurrence of the PVI-alone strategy with reference to the PVI-plus strategy were 1.456 (95% confidence interval [CI] [0.864-2.452]) in the substrate group, 1.648 (95% CI 0.969-2.801) in the PV trigger group, and 0.937 (95% CI 0.252-3.488) in the non-PV trigger group. No significant interaction between ablation strategy and AF mechanism was observed (P for interaction=0.748). Conclusions This study indicated that the efficacies of the PVI-alone strategy compared with the PVI-plus strategy were consistent across persistent AF with trigger-based and substrate-based mechanisms.

Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03–1.27], P =0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19–2.25], P =0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02–2.86], P =0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P =0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.

Recurrence rates of atrial fibrillation (AF) after pulmonary vein isolation (PVI) are higher in patients with a left atrial low‐voltage area (LVA) than those without. However, the efficacy of LVA guided ablation is still unknown. The purpose of this study—the Efficacy and Safety of Left Atrial Low‐voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation trial (SUPPRESS‐AF trial)—is to elucidate whether LVA guided ablation in addition to PVI is superior to PVI alone in patients with persistent AF. The Osaka Cardiovascular Conference will conduct a multicenter, randomized, open‐label trial aiming to examine whether LVA guided ablation in addition to PVI is superior to PVI alone in patients with persistent AF and LVAs. The primary outcome is the recurrence of AF documented by scheduled or symptom‐driven electrocardiography (ECG) during the 1 year follow‐up period after the index ablation. The key secondary endpoints include all‐cause death, symptomatic stroke, bleeding events, and other complications related to the procedure. A total of 340 patients with an LVA will be enrolled and followed up to 1 year. The SUPPRESS‐AF trial is a randomized controlled trial designed to assess whether LVA guided ablation in addition to PVI is superior to PVI alone for patients with persistent AF and LVAs detected while undergoing their first catheter ablation.

Aims Frailty is associated with prognosis of cardiovascular diseases. However, the significance of frailty in patients with heart failure with preserved ejection fraction (HFpEF) remains to be elucidated. The purpose of this study was to examine the prognostic significance of the Clinical Frailty Scale (CFS) in real‐world patients with HFpEF using data from a prospective multicentre observational study of patients with HFpEF (PURSUIT‐HFpEF study). Method and Results We classified 842 patients with HFpEF enrolled in the PURSUIT‐HFpEF study into two groups using CFS. The registry enrolled patients hospitalized with a diagnosis of decompensated heart failure. Median age was 82 [interquartile range: 77, 87], and 45% of the patients were male. Of 842 patients, 406 were classified as high CFS (CFS ≥ 4, 48%) and 436 as low CFS (CFS ≤ 3, 52%). The primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Patients with high CFS were older (85 vs. 79 years, P

We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown.From the PURSUIT-HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1 year. Primary endpoint was a composite of all-cause death or HF rehospitalization.Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P 0.001) and HF rehospitalization (P 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239-3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402-3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004-1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031-1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211-0.969, P = 0.041) were independently associated with progression from ND/ID to DD.More than one-third of HFpEF patients with ND/ID progressed to DD at 1 year and had poor outcomes. Age, BMI and albumin were independently associated with this progression.UMIN000021831.

The effect of a history of cancer on the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is poorly understood.From the Osaka Acute Coronary Insufficiency Study (OACIS) registry in Osaka, Japan, we enrolled the case data of a total of 3499 patients with AMI treated with PCI between 1998 and 2014, of whom 462 had a cancer history (cancer group, 13.2%) and 3037 did not (non-cancer group, 86.8%). All of the cases were followed for up to five years from discharge.The Kaplan-Meier curve and multivariate analysis using Cox proportional hazards models revealed that all-cause mortality was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR], 2.43; P < 0.001). Deaths from cardiac, cancer, and other causes were treated as competing events, and competing analysis using the cumulative incidence function (CIF) and Fine-Gray model revealed that mortality due to cancer was higher in the cancer group than in the non-cancer group, whereas cardiac mortality was similar between the two groups. The incidences of cardiovascular events, including stroke, recurrent infarction, and heart failure requiring readmission, were also similar between the two groups, although the Kaplan-Meier analysis and univariate Cox proportional hazards model revealed that the incidence of stroke was higher in the cancer group than in the non-cancer group.A history of cancer increased all-cause and cancer mortality among patients with AMI treated with PCI, although it was not associated with cardiovascular events.

The Japanese high-bleeding-risk criteria (Japanese-HBR), modified criteria of the Academic Research Consortium (ARC) HBR, has been recently proposed. We aimed to investigate the prevalence of the ARC-HBR and the Japanese-HBR, and to assess their prognostic significance in patients with acute myocardial infarction (AMI). We applied the ARC-HBR and the Japanese-HBR criteria to the OACIS prospective multicenter acute myocardial infarction registry (12,093 patients, 66 ± 12 years, 9,096 males). The primary endpoint was fatal bleeding (BARC-5). Median follow-up duration was 4.84 [inter-quartile range 1.35, 5.01] years. Prevalence of the ARC-HBR was 43.8%, while that of the Japanese-HBR was 61.8%. Cumulative incidence of fatal bleeding was higher in the ARC-HBR group than in the no ARC-HBR group at 1 year (1.3 vs. 0.6%) and at 5 years (2.0 vs. 0.7%). The Kaplan–Meier curves stratified by the Japanese-HBR criteria more prominently diverged (1.3 vs. 0.2% at 1 year; and 1.9 vs. 0.3% at 5 years). The Japanese-HBR criteria showed superior discriminative performance over the ARC-HBR criteria (C-statistics: 0.677 vs. 0.598, P

Aims Previous studies could not demonstrate any benefit of more intensive ablation in addition to pulmonary vein isolation (PVI) including complex fractionated atrial electrogram (CFAE) and linear ablation for recurrence in the initial catheter ablation of persistent atrial fibrillation (AF). This study aimed to establish the non-inferiority of PVI alone to PVI plus these additional ablation strategies. Methods and results Patients with persistent AF who underwent an initial catheter ablation (n = 512, long-standing persistent AF; 128 cases) were randomly assigned in a 1:1 ratio to either PVI alone (PVI-alone group) or PVI plus CFAE and/or linear ablation (PVI-plus group). After excluding 15 cases who did not receive procedures, we analysed 249 and 248 patients, respectively. The primary endpoint was recurrence of AF, atrial flutter, and/or atrial tachycardia, and the non-inferior margin was set at a hazard ratio of 1.43. In the PVI-plus group, 85.1% of patients had linear ablation and 15.3% CFAE ablation. After 12 months, freedom from the primary endpoint occurred in 71.3% of patients in the PVI-alone group and in 78.3% in the PVI-plus group [hazard ratio = 1.56 (95% confidence interval: 1.10–2.24), non-inferior P = 0.3062]. The procedure-related complication rates were 2.0% in the PVI-alone group and 3.6% in the PVI-plus group (P = 0.199). Conclusion This randomized trial did not establish the non-inferiority of PVI alone to PVI plus linear ablation or CFAE ablation in patients with persistent AF, but implied that the PVI plus strategy was promising to improve the clinical efficacy (NCT03514693).

Background Stent thrombosis (ST) remains a significant medical issue. In particular, longer‐term mortality and clinical predictors after ST occurrence have yet to be elucidated. Methods and Results This was a multicenter, retrospective, observational study. A total of 187 definite ST cases from January 2008 to December 2017 were enrolled, and the long‐term clinical outcomes were investigated. The primary outcome measure was the cumulative mortality after ST occurrence. In addition, independent predictors of mortality were assessed. Among the stent types causing ST, bare‐metal stent, first‐generation drug‐eluting stent, second‐generation drug‐eluting stent, and third‐generation drug‐eluting stent comprised 31.0%, 19.3%, 36.9%, and 6.4% of cases, respectively. Median duration from stent implantation to ST was 680.5 (interquartile range, 33.8–2450.5) days. Cumulative mortality was 14.6%, 17.4%, 21.2%, 24.4%, and 33.8% at 1, 2, 3, 5 and 10 years, respectively. The cumulative mortality did not significantly differ by type of stent, and mortality of late ST was higher than that of early ST and very late ST; however, it did not reach statistical significance after the multivariate analysis. Independent predictors of mortality were hemodialysis (hazard ratio [HR], 7.80; 95% CI, 3.07–19.81; P P =0.008), culprit lesions in the left coronary artery (HR, 2.77; 95% CI, 1.10–6.96; P =0.030), and peak creatine kinase (HR, 1.017; 95% CI, 1.011–1.022; P Conclusions The 10‐year cumulative mortality after ST reached 33.8%. Close follow‐up is thus mandatory for patients with ST, especially with hemodialysis, culprit lesions in the left main trunk and left coronary artery, and high peak creatine kinase.

Background: Little is known about factors associated with elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) at the convalescent stage and their effects on 1-year outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results: This study included 469 patients with HFpEF. Elevated NT-proBNP was defined as the highest quartile. The first 3 quartiles (Q1-Q3) were combined together for comparison with the fourth quartile (Q4). Median NT-proBNP concentrations in Q1-Q3 and Q4 were 669 and 3,504 pg/mL, respectively. Multivariate logistic regression analysis revealed that low albumin (odds ratio [OR] 2.44; 95% confidence interval [CI] 1.35-4.39; P=0.003), low estimated glomerular filtration rate (OR 5.83; 95% CI 3.46-9.83; P

Background: Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown. Methods and Results: Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P

Background: Studies comparing the cardiac consequences of hydrophilic and lipophilic statins in experimental and clinical practice settings have produced inconsistent results. In particular, evidence focusing on diabetic patients after acute myocardial infarction (AMI) is lacking. Methods and Results: From the Osaka Acute Coronary Insufficiency Study (OACIS) registry database, 1,752 diabetic patients with AMI who were discharged with a prescription for statins were studied. Long-term outcomes were compared between hydrophilic and lipophilic statins, including all-cause death, recurrent myocardial infarction (re-MI) and admission for heart failure (HF) and a composite of these (major adverse cardiac events; MACE). During a median follow-up period of 1,059 days, all-cause death, non-fatal re-MI, admission for HF, and MACE occurred in 95, 89, 112 and 249 patients, respectively. Although there was no significant difference between statins in the risk of all-cause death, re-MI and MACE, the risk of HF admission was significantly lower in patients with hydrophilic than lipophilic statins before (adjusted hazard ratio [aHR], 0.560; 95% CI: 0.345–0.911, P=0.019) and after (aHR, 0.584; 95% CI: 0.389–0.876, P=0.009) propensity score matching. Hydrophilic statin use was consistently associated with lower risk for HF admission than lipophilic statins across the subgroup categories. Conclusions: In the present diabetic patients with AMI, hydrophilic statins were associated with a lower risk of admission for HF than lipophilic statins.

Women experience more severe arrhythmogenic substrates. This study hypothesized that an extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might be effective for women, whereas the PVI alone strategy (PVI-alone) might be sufficient for men to maintain sinus rhythm. The aim of this study was to test this hypothesis.Methods and Results: This study is a post-hoc subanalysis of the EARNEST-PVI trial focusing on sex differences in the efficacies of different ablation strategies. The EARNEST-PVI trial was a prospective, multicenter, randomized, and open-label non-inferiority trial in patients with persistent AF. The primary endpoint was recurrence of AF, atrial flutter, or atrial tachycardia. The EARNEST-PVI trial randomized 376 (76%) men (PVI-alone 186, PVI-plus 190) and 121 (24%) women (PVI-alone 63, PVI-plus 58). The event rate was significantly lower for men and numerically lower for women in the PVI-plus than the PVI-alone group, and there was no interaction between men and women (hazard ratio, 0.641; 95% confidence interval, 0.417-0.985; P value, 0.043 for men vs. hazard ratio, 0.661; 95% confidence interval, 0.352-1.240; P value, 0.197 for women; P value for interaction, 0.989).The superiority of the extensive ablation strategy vs. the PVI-alone strategy for persistent AF was consistent across both sexes.

Background The previous large‐scale randomized controlled trial showed that routine thrombus aspiration (TA) during percutaneous coronary intervention (PCI) was associated with an increased risk of stroke. However, real‐world clinical evidence is still limited. Methods and Results We investigated the association between manual TA and stroke risk during primary PCI in the OACIS (Osaka Acute Coronary Insufficiency Study) database (N=12 093). The OACIS is a prospective, multicenter registry of myocardial infarction. The primary end point of the present study is stroke at 7 days. A total of 9147 patients who underwent primary PCI within 24 hours of hospitalization were finally analyzed (TA group, n=4448, versus non‐TA group, n=4699 patients). TA was independently associated with risk of stroke at 7 days (odds ratio [OR], 1.92 [95% CI, 1.19‒3.12]; P =0.008) in the simple logistic regression model, while the multilevel random effects logistic regression model with hospital treated as a random effect showed that manual TA was not associated with incremental risk of stroke at 7 days (OR, 0.91 [95% CI, 0.71‒1.16]; P =0.435). The 7‐day stroke risk of manual TA was significantly heterogeneous in different institutions ( P for interaction =0.007). Conclusions Manual TA during primary PCI for patients with acute myocardial infarction was independently associated with the overall increased risk of periprocedural stroke. However, this result was substantially skewed because of institution specific risk variation, suggesting that the periprocedural stroke may be preventable by prudent PCI procedure or appropriate periprocedural management. Registration URL: https://upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000005464 . Unique identifier: UMIN000004575.

To investigate the difference in the prognostic impact of loop diuretics in patients with acute myocardial infarction (AMI) based on plasma volume status, a total of 3,364 survivors of AMI who were registered in the large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed by the estimated plasma volume status (ePVS) that was calculated based on a weight- and hematocrit-based formula at discharge. The endpoint was a composite endpoint of all-cause death and rehospitalization due to heart failure for 5 years. During a median follow-up period of 1.9 years, 90 and 223 patients had events in the groups with low ePVS (median value of 4.07%) and high ePVS (≥4.07%), respectively. Multivariable Cox regression analysis showed that loop diuretics use was independently associated with an increased risk of the composite endpoint in the low ePVS group (hazard ratio [HR], 2.572; 95% confidence interval [CI], 1.386-4.771; p = 0.002), but not in the high ePVS group (HR, 1.028; 95% CI, 0.698-1.512; p = 0.890). These results were unchanged even in the propensity-score matched cohorts. There was no heterogeneity in the increased risk of the primary endpoints between various patient characteristics and loop diuretic use in the matched cohorts. In conclusion, prescription of loop diuretics at discharge was associated with increased risk of poor long-term prognosis in patients with AMI without PV expansion, but not with PV expansion. Therefore, careful observation is needed when loop diuretics are prescribed for AMI patients without PV expansion.

Aims We aimed to establish a practical method for the assessment of tradeoff between thrombotic and bleeding risks. Methods We aimed to investigate the balance between bleeding risk and coronary thrombotic risk according to the number of the Academic Research Consortium for high bleeding risk (ARC-HBR) criteria in the multicenter prospective ST/non-ST elevation myocardial infarction (STEMI/NSTEMI) registry (N=12,093). Patients were divided as follows by the number of ARC-HBR criteria fulfilled: group 0, 0 major with ≤ 1 minor (N=6,792); group 1, 1 major with 0 minor (N=1,705); group 2, 0 major with ≥ 2 minors (N=790); group 3, 1 major with ≥ 1 minor (N=1,709); group 4, 2 majors with ≥ 0 minors (N=861); and group 5, ≥ 3 majors with ≥ 0 minor (N=236). We assessed the acute-phase absolute risk differences between bleeding and coronary thrombotic events in each group. Results At 7-day follow-up, all patients (groups 0-5) had a higher risk of major bleeding than that of any myocardial infarction (MI). Patients at ARC-HBR (groups 1-5) had a balanced risk between fatal MI and fatal bleeding, whereas patients at non-ARC-HBR (group 0) had a higher risk of fatal MI than that of fatal bleeding. Conclusions All STEMI/NSTEMI patients have a relatively high risk of major bleeding as compared with the risk of any MI in the acute phase. The ARC-HBR criteria would be a practical tool for assessing the tradeoff between fatal bleeding and fatal MI risks. This practical assessment would be helpful for the optimal decision-making of appropriate treatment strategy considering the balance between bleeding and coronary thrombotic risks.

ObjectiveThe pathophysiological heterogeneity of heart failure with preserved ejection fraction (HFpEF) makes the conventional ‘one-size-fits-all’ treatment approach difficult. We aimed to develop a stratification methodology to identify distinct subphenotypes of acute HFpEF using the latent class analysis.MethodsWe established a prospective, multicentre registry of acute decompensated HFpEF. Primary candidates for latent class analysis were patient data on hospital admission (160 features). The patient subset was categorised based on enrolment period into a derivation cohort (2016–2018; n=623) and a validation cohort (2019–2020; n=472). After excluding features with significant missingness and high degree of correlation, 83 features were finally included in the analysis.ResultsThe analysis subclassified patients (derivation cohort) into 4 groups: group 1 (n=215, 34.5%), characterised by arrythmia triggering (especially atrial fibrillation) and a lower comorbidity burden; group 2 (n=77, 12.4%), with substantially elevated blood pressure and worse classical HFpEF echocardiographic features; group 3 (n=149, 23.9%), with the highest level of GGT and total bilirubin and frequent previous hospitalisation for HF and group 4 (n=182, 29.2%), with infection-triggered HF hospitalisation, high C reactive protein and worse nutritional status. The primary end point—a composite of all-cause death and HF readmission—significantly differed between the groups (log-rank pConclusionsThis study indicated the feasibility of clinical application of the latent class analysis in a highly heterogeneous cohort of patients with acute HFpEF. Patients can be divided into 4 phenotypes with distinct patient characteristics and clinical outcomes.Trial registration numberUMIN000021831.

BACKGROUND Although diastolic dysfunction is important pathophysiology in heart failure with preserved ejection fraction (HFpEF), its prognostic impact in HFpEF patients, including those with atrial fibrillation (AF), remains to be elucidated.Methods and Results:We included the data for 863 patients (321 patients with AF) registered in a prospective multicenter observational study of patients with HFpEF. Patients were divided into 3 groups according to the 2016 ASE/EACVI recommendations. The primary endpoint was a composite of all-cause death or HF rehospitalization. Median age was 83 years, and 55.5% were female. 196 (22.7%) were classified with normal diastolic function (ND), 253 (29.3%) with indeterminate (ID) and 414 (48.0%) with diastolic dysfunction (DD). The primary endpoint occurred more frequently in patients with DD than in those with ND or ID (log-rank P

Background Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. Methods We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. Results Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p Conclusion An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

When atrial fibrillation (AF) is initiated by a single or several non-pulmonary vein (PV) trigger ectopic beats, mapping the ectopy is often difficult, requiring a number of electrical cardioversion applications. Nifekalant is a rapidly activating delayed rectifier potassium channel (IKr) blocker which may suppress AF initiation without inhibiting ectopy development, thereby allowing the target ectopy to be mapped. To assess the efficacy of nifekalant in the ablation of non-PV ectopies that are unmappable due to easily initiated AF. Eleven consecutive patients were administered nifekalant to map a non-PV ectopy that was unmappable using a conventional method due to easily initiated AF. Nifekalant was intravenously administered as a bolus dose of 0.2 mg/kg, and electrical cardioversion was delivered. Additional boluses of 0.2 mg/kg were repeatedly administered until AF initiation was prevented or until the appearance of significant prolongation of QT interval. AF suppression without inhibition of ectopy development was achieved in 7 patients. These patients had a higher rate of acute elimination of the ectopy than the remaining 4 patients without AF suppression (7 [100%] vs. 1 [25%] patients, p = 0.024). In addition, patients with suppression of AF initiation had a higher AF recurrence-free rate than those without (7 [100%] vs. 1 [25%] patients, p = 0.024). Nifekalant administration appears useful in the ablation of non-PV ectopies that easily initiate AF.

Background: Left ventricular reverse remodeling (LVRR) is a favorable response in non-ischemic, non-valvular cardiomyopathy (NICM) patients. Recently, 18-lead body surface electrocardiography (ECG), the standard 12-lead ECG with synthesized right-sided/posterior chest leads, has been developed, but its predictive value for LVRR has not been evaluated. Methods and Results: Of 216 consecutive hospitalized NICM patients with LV ejection fraction (LVEF) ≤35%, we studied 125 who received optimization of their heart failure treatment and had 18-lead ECG and echocardiography data available for evaluating LVRR, defined as an absolute increase in LVEF ≥10% concomitant with LVEF ≥35% after 1-year optimized treatment. Most 18-lead ECG parameters in the NICM patients differed from those in 312 age- and body mass index-matched subjects with normal echocardiography. LVRR occurred in 59 NICM patients and they had a larger QRS amplitude in the limb leads (I, II, aVR, and aVF), precordial leads (V3–V6), and synthesized leads (syn-V4R–5R), decreased QRS axis and duration, and lower prevalence of fragmented QRS than those without LVRR. The ECG score using 3 selected parameters (QRS amplitude in aVR ≥675 µV; QRS duration

A 70-year-old man with dyspnea was admitted to our department and received standard therapy for recurrent heart failure. He was diagnosed with polycystic kidney disease (PKD) in his thirties and received hemodialysis for 4 years before undergoing renal transplantation at age 45. Although his left ventricular ejection fraction (LVEF) was preserved in his 50s, LVEF decreased progressively from 61% to 24%, while left ventricular diastolic dimension (LVDd) increased from 54 mm to 65 mm between 63 and 69 years of age. Right ventricular endomyocardial biopsy demonstrated myocardial disarray and interstitial fibrosis. Genetic analysis identified a heterozygous frameshift mutation in PKD1, which encodes polycystin-1, a major causative gene of PKD. We detected PKD1 protein expression in myocardial tissue by immunostaining. Recent epidemiological studies and animal models have clarified the pathological correlation between ventricular contractile dysfunction and PKD1 function. Here, we present a case of old-age onset progressive cardiac contractile dysfunction with a PKD1 gene mutation.

Background Atrial fibrillation (AF) and ventricular arrhythmias (VAs) are associated with increased morbidity and mortality. However, data are lacking concerning the association of AF and VAs. This study aimed to clarify the association between AF and VAs and to investigate the effect of amiodarone on the incidence of VAs in patients with implantable cardioverter defibrillators (ICDs). Methods and results We enrolled 612 patients who had ICDs or who underwent cardiac resynchronization therapy with a defibrillator (CRT-D) and classified them into two groups (sinus rhythm [SR] group, n = 427; AF group, n = 185) according to their basal rhythm at enrollment. Patients with paroxysmal AF were grouped into the AF group. The incidence of VAs, i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF), was significantly lower in the AF group than in the SR group (0.54 vs 0.95 episodes/person/year, P = 0.032). Furthermore, amiodarone use was significantly higher in the AF group than in the SR group (P = 0.003). Non-use of amiodarone was associated with a significant increase in the occurrence of VT/VF in the two groups. This beneficial suppressive effect of amiodarone on the incidence of VT/VF was present in the AF group regardless of left ventricular ejection fraction (LVEF). However, this effect of amiodarone was present only in patients with LVEF ≥ 40% in the SR group. Conclusions Amiodarone was negatively associated with VT/VF occurrence and was frequently used in ICD/CRT-D patients with AF. VT/VF was controlled by amiodarone in all cases in the AF group but only in patients with an LVEF ≥ 40% in the SR group.

The effect of a history of cancer on the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is poorly understood.From the Osaka Acute Coronary Insufficiency Study (OACIS) registry in Osaka, Japan, we enrolled the case data of a total of 3499 patients with AMI treated with PCI between 1998 and 2014, of whom 462 had a cancer history (cancer group, 13.2%) and 3037 did not (non-cancer group, 86.8%). All of the cases were followed for up to five years from discharge.The Kaplan-Meier curve and multivariate analysis using Cox proportional hazards models revealed that all-cause mortality was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR], 2.43; P0.001). Deaths from cardiac, cancer, and other causes were treated as competing events, and competing analysis using the cumulative incidence function (CIF) and Fine-Gray model revealed that mortality due to cancer was higher in the cancer group than in the non-cancer group, whereas cardiac mortality was similar between the two groups. The incidences of cardiovascular events, including stroke, recurrent infarction, and heart failure requiring readmission, were also similar between the two groups, although the Kaplan-Meier analysis and univariate Cox proportional hazards model revealed that the incidence of stroke was higher in the cancer group than in the non-cancer group.A history of cancer increased all-cause and cancer mortality among patients with AMI treated with PCI, although it was not associated with cardiovascular events.

Background: Estimated plasma volume status (ePVS) is a well-validated prognostic indicator in heart failure. However, it remains unclear whether ePVS has prognostic significance in patients with acute myocardial infarction (AMI). Moreover, there is no available information on its additive effect with the Global Registry of Acute Coronary Events (GRACE) risk score in AMI patients. Methods: Data were obtained from the Osaka Acute Coronary Insufficiency Study (OACIS) registry database. Patients whose data were available for ePVS derived from Hakim’s formula and the GRACE risk score were studied. The primary endpoints were in-hospital and 5-year mortality. Results: Of 3930 patients, 206 and 200 patients died during hospitalization and 5 years after discharge, respectively. After adjustment, ePVS remained an independent predictor of in-hospital death (OR:1.02, 95% CI: 1.00–1.04, p = 0.036), and 5-year mortality(HR:1.03, 95% CI: 1.01–1.04, p