Acute cardiovascular disease, such as acute myocardial infarction and aortic disease, can lead to a serious life-threatening state within minutes to hours, so early accurate diagnosis, and appropriate treatment without delay are essential. To provide high-quality and timely treatment, 24-h availability of medical staff and cardiologists, as well as a cardiac catheterization laboratory are needed. In Japan, the number of patients with acute cardiovascular disease is increasing with the aging population and westernization of lifestyle; however, workstyle reforms for physicians, including a policy to limit overtime work, have been legislated. Under these conditions, it is necessary to centralize hospitals that treat cardiovascular emergency diseases as high-volume centers and build a patient triage system for allocating patients before hospital arrival. The prehospital 12-lead electrocardiogram (ECG) plays a central role in prehospital diagnosis and triage, and its importance will increase in future. We discuss the current and future state of the cardiovascular emergency medical care system utilizing prehospital 12-lead ECG in urban areas of Japan.

Background: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.

Conclusions: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.

Background:Two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) can predict the prognosis. This study investigated the clinical significance of a serial 3D-STE can predict the prognosis after onset of STEMI.

Methods and Results:This study enrolled 272 patients (mean age, 65 years) with first-time STEMI treated with reperfusion therapy. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Within 1 year, 19 patients who experienced major adverse cardiac events (MACE; cardiac death, heart failure requiring hospitalization) were excluded. Among the 253 patients, 248 were examined with follow-up echocardiography. The patients were followed up for a median of 108 months (interquartile range: 96–129 months). The primary endpoint was the occurrence of a MACE; 45 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 2D-global longitudinal strain (GLS) and 3D-GLS at 1-year indices were significant predictors of MACE. The Kaplan-Meier curve demonstrated that a 3D-GLS of >−13.1 was an independent predictor for MACE (log-rank χ²=165.5, P<0.0001). The deterioration of 3D-GLS at 1 year was a significant prognosticator (log-rank χ²=36.7, P<0.0001).

Conclusions:The deterioration of 3D-GLS measured by STE at 1 year after the onset of STEMI is the strongest predictor of long-term prognosis.

Background:The PARIS and CREDO-Kyoto risk scores were developed to identify patients at risks of thrombotic and bleeding events individually after percutaneous coronary intervention (PCI). However, these scores have not been well validated in different cohorts.

Methods and Results:This 2-center registry enrolled 905 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into 3 groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding events. Of 905 patients, 230 (25%) and 219 (24%) had high thrombotic and bleeding risks, respectively, with the PARIS scores, compared with 78 (9%) and 50 (6%) patients, respectively, with the CREDO-Kyoto scores. According to the 2 scores, >50% of patients with high bleeding risk had concomitant high thrombotic risk. During the mean follow-up period of 714 days, 163 (18.0%) and 95 (10.5%) patients experienced ischemic and bleeding events, respectively. Both PARIS and CREDO-Kyoto scores were significantly associated with ischemic and bleeding events after primary PCI. For ischemic events, the CREDO-Kyoto rather than PARIS thrombotic risk score had better diagnostic ability.

Conclusions:In the present Japanese cohort of acute MI patients undergoing contemporary primary PCI, the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores were discriminative for predicting ischemic and bleeding events.

Background:Acute myocardial infarction (AMI) patients with low body mass index (BMI) exhibit worse clinical outcomes than obese patients; however, to our knowledge, no prospective, nationwide study has assessed the effect of BMI on the clinical outcomes of AMI patients.

Methods and Results:In this multi-center, prospective, nationwide Japanese trial, 2,373 AMI patients who underwent emergent percutaneous coronary intervention within 12 h of onset from the Japanese AMI Registry (JAMIR) were identified. Patients were divided into the following 4 groups based on their BMI at admission: Q1 group (BMI <18.5 kg/m², n=133), Q2 group (18.5≤BMI<25.0 kg/m², n=1,424), Q3 group (25.0≤BMI<30.0 kg/m², n=672), and Q4 group (30.0 kg/m²≤BMI, n=144). The primary endpoint was all-cause death, and the secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. The median follow-up period was 358 days. Q1 patients were older and had lower prevalence of coronary risk factors. Q1 patients also had higher all-cause mortality and higher incidence of secondary endpoints than normal-weight or obese AMI patients. Multivariate analysis showed that low BMI (Q1 group) was an independent predictor for primary endpoint.

Conclusions:AMI patients with low BMI had fewer coronary risk factors but worse clinical outcomes than normal-weight or obese patients.

Background:Application of drug-coated balloons (DCBs) is popular for the treatment of percutaneous coronary intervention (PCI). A new DCB has been designed as ultrasound-controlled paclitaxel releasing. This study was conducted to determine whether a DCB-only strategy has a similar safety profile and equal angiographic and clinical outcomes to DES implantation in primary ST-elevation myocardial infarction (STEMI) patients, as well as determine the efficiency and safety of this new DCB.

Methods and Results:Overall, 184 pretreated STEMI patients were randomized into DCB and DES groups with a 1:1 allocation. The main study end-point was late lumen loss (LLL) during the 9 months after PCI. Late lumen loss was reported to be 0.24±0.39 mm in the DCB group and 0.31±0.38 mm in the DES group (P=0.215). Diameter stenosis was 28.27±15.35% in the DCB group and 25.73±15.41% in the DES group (P=0.312). Major adverse cardiovascular events (MACEs) were reported in 3 patients (3.4%) in the DCB group and 4 patients (4.7%) in the DES group (P=0.718). TLR and TVR in the DCB group was 2.3%, 3.4% and 2.4%, 3.5% in the DES group (P=1.000), respectively. No cardiac death and stent thrombosis (ST) was found in the DCB group at 12 months clinical follow up.

Conclusions:The DCB-only strategy showed good angiographic and clinical outcomes in the 9- and 12-month follow-up periods, respectively. The VasoguardTM DCB is safe and feasible to treat STEMI patients.

Background:Previous studies have reported that acute myocardial infarction (AMI) related to left anterior descending (LAD) lesion is associated with worse outcomes than left circumflex artery (LCX) or right coronary artery (RCA) lesions. However, it is unknown whether those relationships are still present in the contemporary era of primary percutaneous coronary intervention (PCI), using newer generation drug-eluting stents and potent antiplatelet agents.

Methods and Results:This study is a sub-analysis of the Japan AMI Registry (JAMIR), a multicenter, prospective registry enrolling 3,411 AMI patients between December 2015 and May 2017. Among them, 2,780 patients undergoing primary PCI for only a culprit vessel were included and stratified based on infarction-related artery type (LAD, LCX, and RCA). The primary outcome was 1-year cardiovascular death. The overall incidence of cardiovascular death was 3.4%. Patients with LAD infarction had highest incidence of cardiovascular death compared to patients with LCX and RCA infarction (4.8%, 1.3%, and 2.4%, respectively); however, landmark analysis showed that culprit vessel had no significant effect on cardiovascular death if a patient survived 30 days after primary PCI. LAD lesion infarction was an independent risk factor for cardiovascular death in adjusted Cox regression analysis.

Conclusions:The present sub-analysis of the JAMIR demonstrated that LAD infarction is still associated with worse outcomes, especially during the first 30 days, even in the contemporary era of PCI.

Background:Because no data were available regarding the effect of preexisting left ventricular filling pressure (LVFP) on clinical outcomes in patients with acute myocardial infarction (AMI), we evaluated whether preexisting high LVFP can determine outcomes of subsequent AMI events.

Methods and Results:Among 399,613 subjects who underwent echocardiography for various reason from August 2004 to June 2019, 231 had experienced subsequent AMI and were stratified according to preexisting LVFP: low LVFP (E/e’ ≤14) and high LVFP (E/e’ >14). The primary outcome was cardiac death at 30 days and 1 year after AMI. Overall, 19.5% had high LVFP prior to AMI events. Preexisting high LVFP was associated with an increased risk of cardiac death at 30 days (3.8% vs. 11.6%; adjusted hazard ratio (HR) 4.56, 95% confidence interval (CI) 1.20–17.24, P=0.026) and 1 year after AMI (7.9% vs. 35.9%; adjusted HR 4.14, 95% CI 1.79–9.57, P<0.001). Preexisting E/e’ as a continuous value was significantly associated with 1-year risk of cardiac death (adjusted HR 1.08, 95% CI 1.02–1.15, P=0.007). Follow-up echocardiography showed that patients with high LVFP did not show improvement in systolic or diastolic function.

Conclusions:Preexisting high LVFP was associated with poor clinical course and 1-year cardiac death after subsequent AMI, as well as no improvement in systolic or diastolic function.

Background:The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).

Methods and Results:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O₂(PO₂), partial pressure of CO₂(PCO₂) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset.

Conclusions:The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.

Background:Although bystanders’ performance is important to improve outcomes of patients after cardiac arrests, few studies have investigated the barriers of bystanders, including those who could not perform cardiopulmonary resuscitation or any other rescue actions in emergency situations. This study aimed to assess the relationship between the psychological barriers of laypersons who encountered emergency situations and their rescue actions.

Methods and Results:A questionnaire survey was conducted and this included laypersons who had encountered emergency situations during the last 5 years. Six questions were about the psychological barriers and 8 questions were about the laypersons’ rescue actions. The primary outcome was any rescue actions performed by laypersons in an actual emergency situation. Overall, 7,827 (92.8%) of 8,430 laypersons responded; of them, 1,361 (16.1%) had encountered emergency situations during the last 5 years, and 1,220 (14.5%) were eligible for inclusion in the analyses. Of the 6 psychological barriers, “fear of approaching a collapsed person” (adjusted odds ratio [AOR] 0.50; 95% confidence interval [95% CI] 0.32–0.79) and “difficulties in judging whether to perform any rescue action” (AOR 0.63; 95% CI 0.40–0.99) were significantly associated with performing any rescue actions.

Conclusions:The fear of approaching a collapsed person and difficulties in judging whether to take any actions were identified as the psychological barriers in performing any rescue actions by laypersons who encountered emergency situations.

Background:The predictive role of the vasoactive-inotropic score (VIS) for clinical outcomes after venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock is not well known. This study investigated the predictive value of VIS on in-hospital outcomes and the determination of optimal timing for the initiation of VA-ECMO.

Methods and Results:Overall, 160 patients with cardiogenic shock requiring VA-ECMO who were treated between December 2012 and August 2018 were analyzed. The in-hospital outcomes according to VIS were compared. Pre-ECMO VIS had an area under the receiver-operating characteristic curve (AUC) of 0.60 (P=0.03) for the prediction of in-hospital death. When the patients were divided into the high (≥32) and low (<32) VIS groups, the high VIS group had a higher rate of in-hospital death (P=0.002) and a lower rate of ECMO weaning (P=0.004). The difference in in-hospital death according to VIS was significant only in patients with a cardiogenic shock of non-ischemic etiology (P=0.01). Extracorporeal cardiopulmonary resuscitation (hazard ratio [HR], 1.99), age (HR, 1.02), pre-ECMO lactate (HR, 1.06), and VIS ≥32 (HR, 2.46) were independently predictive of in-hospital death.

Conclusions:Among patients with cardiogenic shock requiring VA-ECMO, the initiation of VA-ECMO before reaching high VIS (≥32) showed better in-hospital outcomes, suggesting that VIS may be a potential marker for determining the initiation of hemodynamic support with VA-ECMO.

Background:Tolvaptan is an orally administered aquaretic drug indicated for patients with congestive heart failure (CHF) to remove excess fluid. OPC-61815, a prodrug of tolvaptan with improved water solubility, is considered suitable for intravenous (IV) administration. This Phase II study investigated the OPC-61815 dose that would result in an exposure equivalent to tolvaptan 15 mg.

Methods and Results:We conducted a multicenter, randomized study in Japanese patients aged 20–85 years with CHF and volume overload despite treatment with diuretics other than vasopressin antagonists. Patients received IV OPC-61815 2 mg (n=13), 4 mg (n=12), 8 mg (n=12), 16 mg (n=11), or oral tolvaptan 15 mg (n=12). The primary endpoint was tolvaptan exposure on treatment Day 1; efficacy and safety were also assessed. Tolvaptan exposure increased in a dose-dependent manner following a single IV administration of OPC-61815; the exposure following an IV dose of OPC-61815 16 mg was similar to that of a tolvaptan 15-mg tablet, with no marked differences in safety or tolerability. OPC-61815 increased urine volume from baseline, resulting in decreased body weight and improved lower limb edema. No notable safety concerns were observed.

Conclusions:In this first study of OPC-61815 in patients with CHF, exposure following a single IV administration of OPC-61815 16 mg was comparable with a single oral administration of tolvaptan 15 mg, with no safety concerns.

Background:Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).

Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m²) and TD (urinary β-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170–871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality.

Conclusions:As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Background:The impact of promotional tweets from the official journal account (forCirculation JournalandCirculation Reports) on article viewership has not been thoroughly evaluated.

Methods and Results:We retrospectively collected journal viewership data forCirculation JournalandCirculation Reportsfrom March 2021 to August 2021. We compared viewership between articles with (n=15) and without (n=250) tweets. After 1 : 4 propensity score matching (15 tweeted articles and 60 non-tweeted matched controls), journal viewership metrics within 7 days of the tweeting date (and the hypothetical tweeting date), was larger in tweeted articles than non-tweeted articles (median [interquartile range] Abstract page views 89 [60–104] vs. 18 [8–41]).

Conclusions:This pilot study suggests a positive relationship between journal-posted promotional tweets and article viewership.

Background:Atrial fibrillation (AF) increases the risk of stroke and death. Oral anticoagulants (OAC) are highly effective in reducing the risk of stroke, and direct oral anticoagulants (DOAC) became available worldwide in 2011.

Methods and Results:The Fushimi AF Registry is an on-going prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. The study cohort consisted of 4,489 patients (mean age 73.6 years, 59.6% male, mean CHADS₂score 2.03), enrolled in 2011–2017. From 2011 to 2021, antithrombotic therapy has undergone a major transition; the proportion of patients receiving OAC has increased from 53% to 70%, with a steady uptake of DOAC (from 2% to 52%), whereas the proportion of patients receiving antiplatelet agents has decreased from 32% to 14%. Over a median follow-up of 5.1 years, the incidence of stroke/systemic embolism (SE), major bleeding, and all-cause death was 2.2%, 1.9%, and 4.9% per patient-year, respectively. The incidence of stroke/SE (1.6% vs. 2.3%; P<0.01), major bleeding (1.6% vs. 2.0%; P=0.07), and death (4.2% vs. 5.0%; P<0.01) was lower among patients enrolled in 2014–2017 than in 2011–2013, despite comparable baseline characteristics (age 73.2 vs. 73.7 years, CHADS₂score 2.03 vs. 2.04, and HAS-BLED score 1.67 vs. 1.77, respectively).

Conclusions:Over the past 10 years, there has been a major transition in antithrombotic therapy and a decline in the incidence of adverse events in AF patients.