Toshiharu Fujii

BleeMACS: rationale and design of the study.

Background Bleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital events and absence of patients treated with new antiplatelet agents in the current era of widespread use of percutaneous coronary intervention. Design The BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) project is a multicenter investigator-initiated international retrospective registry that enrolled more than 15 000 patients discharged with a definitive diagnosis of acute coronary syndrome and treated with percutaneous revascularization. The primary end point is the incidence of major bleeding events requiring hospitalization and/or red cell transfusion concentrates within 1 year. An integer risk score for bleeding within the first year after hospital discharge will be developed from a multivariate competing-risks regression. Conclusion The BleeMACS registry collaborative will allow development and validation of a risk score for prediction of major bleeding during follow-up for patients receiving contemporary therapies for acute coronary syndrome.

Impact of transport pathways on the time from symptom onset of ST-segment elevation myocardial infarction to door of coronary intervention facility

BACKGROUND Reducing total ischemic time is important in achieving better outcome in ST-segment elevation myocardial infarction (STEMI). Although the onset-to-door (OTD) time accounts for a large portion of the total ischemic time, factors affecting prolongation of the OTD time are not established. PURPOSE The purpose of this study was to determine the impact of transport pathways on OTD time in patients with STEMI. METHODS AND SUBJECTS We retrospectively studied 416 STEMI patients who were divided into 4 groups according to their transport pathways; Group 1 (n = 41): self-transportation to percutaneous coronary intervention (PCI) facility; Group 2 (n = 215): emergency medical service (EMS) transportation to PCI facility; Group 3 (n = 103): self-transportation to non-PCI facility; and Group 4 (n = 57): EMS transportation to non-PCI facility. OTD time was compared among the 4 groups. ESSENTIAL RESULTS Median OTD time for all groups combined was 113 (63-228.8)min [Group 1, 145 (70-256.5); Group 2, 71 (49-108); Group 3, 260 (142-433); and Group 4, 184 (130-256)min]. OTD time for EMS users (Groups 2 and 4) was 138 min shorter than non-EMS users (Groups 1 and 3). Inter-hospital transportation (Groups 3 and 4) prolonged OTD by a median of 132 min compared with direct transportation to PCI facility (Groups 1 and 2). Older age, history of myocardial infarction, prior PCI, shock at onset, high Killip classification, and high GRACE Risk Score were significantly more frequent in EMS users. PRINCIPAL CONCLUSIONS Self-transportation without EMS and inter-hospital transportation were significant factors causing prolongation of the OTD time. Approximately 35% of STEMI patients did not use EMS and 21% of patients were transported to non-PCI facilities even though they called EMS. Awareness in the community as well as among medical professionals to reduce total ischemic time of STEMI is necessary; this involves educating the general public and EMS crews.

Transradial intervention for patients with ST elevation myocardial infarction with or without cardiogenic shock

To compare clinical outcomes between transradial (TRI) and transfemoral intervention (TFI) in primary percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction (STEMI) with or without shock.

Impact of blood transfusion on in-hospital myocardial infarctions according to patterns of acute coronary syndrome: Insights from the BleeMACS registry

BACKGROUND Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS). METHODS Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS). RESULTS Overall, 13,975 patients were included: mean age was 64.1years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end-point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244-7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients. CONCLUSIONS In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis.

Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: The BleeMACS score

BACKGROUND Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients. METHODS The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI. RESULTS Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts. CONCLUSIONS The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.govIdentifier: NCT02466854.

Impact of the origin of the collateral feeding donor artery on short-term mortality in ST-elevation myocardial infarction with comorbid chronic total occlusion

BACKGROUND Patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD) have higher mortality, especially with comorbid chronic total occlusion (CTO). The origin of collateral flow to the CTO segment has not been studied in regard to short-term mortality. This study examined the impact of collateral feeding donor arteries from an infarct-related artery (IRA) or non-IRA to the comorbid CTO segment in regard to STEMI short-term mortality. METHODS Data from 760 consecutive STEMI patients who underwent primary percutaneous coronary intervention were obtained retrospectively from medical records. The number of vessels involved and origin of the collateral feeding donor artery were evaluated using angiograms from the primary percutaneous coronary intervention. The study population was divided into patients with: single-vessel disease (SVD) (n=483), MVD without CTO (n=208), and MVD with CTO (n=64). All CTO segments had collateral flow from an IRA (n=23) or non-IRA (n=46). All-cause mortality (30-day) was analyzed. RESULTS Compared to SVD and MVD without CTO, MVD with comorbid CTO had a higher mortality (5.4% vs. 15.9% vs. 24.6%, P<0.0001, respectively). Of patients with CTO, those with collateral flow from the IRA had significantly higher mortality than the non-IRA group (52.2% vs. 10.9%, P<0.0001). Collateral flow from the IRA was extracted as an independent predictor associated with 30-day all-cause mortality using a multivariate Cox proportional hazards model (hazard ratio 4.71, 95% confidence interval 1.60-14.2, P=0.0005). CONCLUSIONS The origin of the collateral donor artery from the IRA had an impact on short-term mortality in STEMI patients with comorbid CTO lesions.

Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods We retrospectively analyzed data from a “real world”, international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903–1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875–6.151) (Pinteraction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.

Altered blood flow in cerebral perforating arteries of rat models of diabetes: A synchrotron radiation microangiographic study toward clinical evaluation of white matter hyperintensities

As altered blood flow in the cerebral perforating arteries (PA) might be related to development of cerebral white matter hyperintensities, we examined whether the hemodynamic relationship of the PA and middle cerebral artery (MCA) is altered in rat models of diabetes, compared with normal rats and a rat model of sinoatrial denervation (blood pressure fluctuation model).

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. Methods and results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8–2.5, P<0.001) and bleedings (HR 1.5, 1.1–2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4–0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3–0.8, P=0.02), statins (RR 0.3, 0.2–0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3–0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6–1.5, P=0.9) were neutral. Conclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Longitudinal analysis of the depressive effects of intravenous amiodarone on depolarization and repolarization: A case report

Intravenous amiodarone (AMD) induces multiple antiarrhythmic effects via blocking of Na(+), Ca(2+), and IKr channels, and beta receptors. A patient on chronic dialysis was administered AMD for nonsustained ventricular tachycardia after successful cardiopulmonary resuscitation. QT prolongation occurred 5 h after AMD administration. AMD was withdrawn at 24 h because of prolonged QTc interval (716 ms), which persisted for a further 48 h (661 ms). Ventricular premature contraction (VPC) was significantly decreased at 7h; however, VPC increased again after discontinuing AMD. Depolarization changes induced by the Na(+)-channel blocking action of AMD were analyzed. There was increasing filtered QRS-duration and duration of low-amplitude signals at voltage <40 µV, and decreasing root-mean-square voltage of signals in the last 40 ms of ventricular late potentials (LPs) within 7 h. However after stopping AMD, LPs were reversed. The blood concentration of AMD reached the effective level within 10 min but decreased immediately to an ineffective level. Onset and disappearance of the VPC-inhibiting effect corresponded to the depressive effect on depolarization but not with the increase in the prolonged repolarization effect and blood concentration. Even if the QT interval is sufficiently prolonged, the Na(+)-channel blocking action is required for AMD to induce the antiarrhythmic effect.