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Abstract Aims The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission. Methods and results The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all‐cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non‐fatal myocardial infarction, or non‐fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow‐up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction

Study objective: This study aimed to investigate whether the incidence of acute myocardial infarction (AMI) and subsequent outcomes over the three years after the Kumamoto earthquake differed from the underlying trend before the earthquake. Design: Quasi-experimental design. Setting: Twenty-one institutions participating from the Kumamoto Prefecture and capable of receiving AMI patients and performing coronary angiography and interventions. Participants: In total 6553 consecutive patients with AMI between 2013 and 2019 were included in this study. Interventions: Interrupted time series analysis. Main outcome measure(s): AMI incidence and following cardiac events after the earthquake. Results: The rate ratio (RR) for AMI incidence after the earthquake was 1.12 (95 % confidence interval [CI]: 1.00–1.25) with reference to that before the earthquake. AMI rates increased among people with diabetes mellitus (RR: 1.20, 95 % CI: 1.01–1.44), those with current smoking (RR: 1.27, 95 % CI: 1.03–1.56), and those with a body mass index >25 kg/m2 (RR: 1.27, 95 % CI: 1.06–1.52). Increased number of AMI patients with onset-to-door time >12 h (RR: 1.46, 95 % CI: 1.02–2.08), a high Killip class on hospital admission (RR: 1.37, 95 % CI: 1.13–1.67), and unperformed emergent coronary angiography (RR: 1.40, 95 % CI: 1.02–1.91) were frequently observed after the earthquake, which may affect following in-hospital cardiac events (RR: 1.49, 95 % CI: 1.03–2.15). Conclusions: The Kumamoto earthquake had an impact on the increase in the incidence of AMI and the following in-hospital cardiac outcomes. Emergency medical care should be ensured in such a way that high-risk patients are managed as usual, especially immediately after earthquake.

Background: Hypertension, diabetes, dyslipidemia and smoking are established coronary risk factors for coronary heart disease in the general population. However, in Japanese patients with acute myocardial infarction (AMI), the impact of the number of coronary risk factors on in-hospital morality remains unclear. Methods: The Japan Acute Myocardial Infarction Registry (JAMIR) is a nationwide real-world database. We examined the association between the number of coronary risk factors and in-hospital mortality. Results: Data were obtained from total of 20462 AMI patients (mean age, 68.8 ± 13.3 years old; 15281 men, 5181 women). The prevalence of hypertension increased with advancing age, while the prevalence of smoking decreased with advancing age. The prevalence of diabetes and dyslipidemia were highest in middle age. A majority (76.9%) of the patients with AMI had at least 1 of these coronary risk factors. Overall, the number of coronary risk factor was relatively less in older subjects and women under 50 years old. Crude in-hospital mortality rates were 10.7%, 10.5%, 7.2%, 5.0% and 4.5% with 0, 1, 2, 3 and 4 risk factors, respectively. After adjusting for age and sex, there was an inverse association between the number of coronary risk factors and the in-hospital mortality (adjusted odds ratio [1.68; 95% confidence interval, 1.20–2.35] among individuals with 0 vs. 4 risk factors). Conclusion: In the present study of Japanese patients with AMI, who received modern medical treatment, in-hospital mortality was inversely related to the number of coronary risk factors. To investigate the underlying reasons for these findings, further studies are needed.

Background: Cardiovascular diseases, including acute myocardial infarction (AMI), are leading causes of death among the Japanese, who have the longest life expectancy in the world. Over the past 50 years in Japan, the percentage of elderly individuals has increased 4-fold, from 5.7% in 1960 to 23.1% in 2010. To explore medical practices and emergency care for AMI in this aging society, the Japan Acute Myocardial Infarction Registry (JAMIR) was established as a nationwide real-world database. Methods: JAMIR conducted retrospective analysis of 20,462 AMI patients (mean age, 68.8 ± 13.3 years; 15,281 men [74.7%]) hospitalized between January 2011 and December 2013. Results: The rates of ambulance use and emergency PCI were 78.9% and 87.9%, respectively. The median door-to-balloon time was 80 min (interquartile range, 53–143 min). Overall in-hospital mortality was 8.3%, including 6.6% due to cardiac death. JAMIR included 4837 patients aged ≥80 years (23.6%). In this age group, patients who underwent PCI (79.9%) had significantly lower in-hospital mortality than those who did not (11.1% vs. 36.9%, P

LCZ696 (sacubitril/valsartan) can lower the risk of cardiovascular events in chronic heart failure. However, it is unclear whether LCZ696 can improve prognosis in patients with acute myocardial infarction (MI). The present study shows that LCZ696 can prevent cardiac rupture after MI, probably due to the suppression of pro-inflammatory cytokines, matrix metalloproteinase-9 activity and aldosterone production, and enhancement of natriuretic peptides in mice. These findings suggest the mechanistic insight of cardioprotective effects of LCZ696 against acute MI, resulting in the belief that LCZ696 might be useful clinically to improve survival after acute MI.

Abstract Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogenic surfaces. Blood samples were obtained at Off- and On-anticoagulant (trough) from 120 consecutive patients with atrial fibrillation (warfarin; n = 29, dabigatran; n = 19, rivaroxaban; n = 47, apixaban; n = 25), which were used for T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip, and to measure plasma concentrations of DOACs at On-anticoagulant. In addition, the two-dimensional area covered by thrombi (%) in the capillary was analyzed every 3 minutes after sample applications. The AR10-AUC30 correlated weakly and negatively with plasma concentrations of DOACs, and the levels at On-anticoagulant were lower in all groups than at Off-anticoagulant. AR10-AUC30 levels at Off- and On-anticoagulant were identical among the groups. The thrombi areas in early phase were significantly larger in rivaroxaban and apixaban than warfarin and dabigatran groups. The findings suggested that visual analysis of the AR-chip can identify the differential inhibitory patterns of warfarin and DOACs on thrombus formation under flow condition.

Background: Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on the patients with microvascular angina (MVA) caused by coronary microvascular dysfunction. Methods and results: We examined CYP2C19 genotypes in patients with MVA (n = 81). MVA was defined as absence of coronary artery stenosis and epicardial spasms, and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. In MVA, the patients with CYP2C19 PM were 34.6% and high sense C-reactive protein (hs-CRP) levels in CYP2C19 PM were significantly higher than that of non-PM group (0.165 ± 0.116 vs. 0.097 ± 0.113 mg/dL, P = 0.026). Moreover, DHET levels in CYP2C19 PM were significantly lower than that of non-PM (10.4 ± 4.58 vs. 15.6 ± 11.1 ng/mL, P = 0.003 (11,12-DHET); 12.1 ± 3.79 vs. 17.3 ± 6.49 ng/mL, P = 0.019 (14,15-DHET)). Conclusions: The decline of EET owing to CYP2C19 variants may affects coronary microvascular dysfunction via chronic inflammation.

BackgroundThe CHADS2 score has mainly been used to predict the likelihood of cerebrovascular accidents in patients with atrial fibrillation. However, increasing attention is being paid to this scoring system for risk stratification of patients with coronary artery disease. We investigated the value of the CHADS2 score in predicting cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation. Methods and ResultsThis was a multicenter, observational cohort study. The subjects had been admitted to one of the participating institutions with coronary artery disease requiring percutaneous coronary intervention. We calculated the CHADS2 scores for 7082 patients (mean age, 69.7 years; males, 71.9%) without clinical evidence of atrial fibrillation. Subjects were subdivided into low‐ (0–1), intermediate‐ (2–3), and high‐score (4–6) groups and followed for 1 year. The end point was a composite of cardiovascular/cerebrovascular death, nonfatal myocardial infarction, and ischemic stroke at 1‐year follow‐up. Rates of triple‐vessel/left main trunk disease correlated positively with CHADS2 score categories. CHADS2 scores among single, double, and triple‐vessel/left main trunk groups were 2 (1–2), 2 (1–3), and 2 (2–3), respectively (P

BackgroundMean amplitude of glycemic excursion (MAGE) is commonly used to gauge the degree of glucose level fluctuations. MAGE plays a significant role in vascular endothelial dysfunction and cardiovascular events in patients with diabetes mellitus (DM), but its significance is not clear in non‐DM patients. Thus, we examined the impact of MAGE and vascular endothelial dysfunction on clinical outcomes in non‐DM patients with coronary artery disease. Methods and ResultsWe followed non‐DM patients (n=65) for 12 months who underwent percutaneous coronary intervention and assessed the relationship among MAGE, reactive hyperemia index (RHI) measured by reactive hyperemia peripheral arterial tonometry as endothelial function, and cardiovascular events. Cardiovascular events analyzed were cardiovascular death, myocardial infarction, unstable angina, and revascularizations. Compared with patients with MAGE

BackgroundPeriprocedural bleeding events are common after percutaneous coronary intervention. We evaluated the association of periprocedural bleeding events with thrombogenicity, which was measured quantitatively by the Total Thrombus‐formation Analysis System equipped with microchips and thrombogenic surfaces (collagen, platelet chip [PL]; collagen plus tissue factor, atheroma chip [AR]). Methods and ResultsBetween August 2013 and March 2016, 313 consecutive patients with coronary artery disease undergoing elective percutaneous coronary intervention were enrolled. They were divided into those with or without periprocedural bleeding events. We determined the bleeding events as composites of major bleeding events defined by the International Society on Thrombosis and Hemostasis and minor bleeding events (eg, minor hematoma, arteriovenous shunt and pseudoaneurysm). Blood samples obtained at percutaneous coronary intervention were analyzed for thrombus formation area under the curve (PL24‐AUC10 for PL chip; AR10‐AUC30 for AR chip) by the Total Thrombus‐formation Analysis System and P2Y12 reaction unit by the VerifyNow system. Periprocedural bleeding events occurred in 37 patients. PL24‐AUC10 levels were significantly lower in patients with such events than those without (P=0.002). Multiple logistic regression analyses showed association between low PL24‐AUC10 levels and periprocedural bleeding events (odds ratio, 2.71 [1.22–5.99]; P=0.01) and association between PL24‐AUC10 and periprocedural bleeding events in 176 patients of the femoral approach group (odds ratio, 2.88 [1.11–7.49]; P=0.03). However, PL24‐AUC10 levels in 127 patients of the radial approach group were not significantly different in patients with or without periprocedural bleeding events. ConclusionsPL24‐AUC10 measured by the Total Thrombus‐formation Analysis System is a potentially useful predictor of periprocedural bleeding events in coronary artery disease patients undergoing elective percutaneous coronary intervention.

BackgroundDrug‐eluting stents are replacing bare‐metal stents, but in‐stent restenosis (ISR) remains a problem. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry evaluates endothelial function noninvasively. We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention. Methods and ResultsRHI was measured before percutaneous coronary intervention and at follow‐up (F/U) angiography (F/U RHI; 6 and 9 months post bare‐metal stents– and drug‐eluting stents– percutaneous coronary intervention, respectively) in 249 consecutive patients. At F/U, ISR (stenosis >50% of diameter) was seen in 68 patients (27.3%). F/U natural logarithm (RHI) was significantly lower in patients with ISR than in those without (0.52±0.23 versus 0.65±0.27, P

BackgroundStatin therapy reduces the risk of cardiovascular events in patients with obstructive coronary artery disease. The aim of the present study was to determine the effects of statins on the prognosis of patients with coronary vasospastic angina (VSA) free of significant atherosclerotic stenosis. Methods and ResultsAfter exclusion of 475 from 1877 consecutive patients who underwent an acetylcholine‐provocation test between January 1991 and December 2010, data of 640 VSA patients without significant organic stenosis of the remaining 1402 were analyzed retrospectively. Propensity score matching was performed to reduce the effect of treatment‐selection bias and possible confounders. The primary endpoint was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and unstable angina. Among the study population, dyslipidemia on admission was identified in 160 of 168 (95.2%) patients of the statin group compared with only 125 of 472 (26.5%) of the no‐statin group. Of the 640 patients, 24 (3.8%) developed MACE. Multivariate Cox hazard regression analysis identified statin therapy as a significant negative predictor of MACE (hazard ratio, 0.11; 95% CI, 0.02–0.84; P=0.033). In the propensity‐score matched cohorts (n=128 each), Kaplan–Meier survival curve showed a better 5‐year MACE‐free survival rate for patients of the statin group compared to the no‐statin group (100% vs 91.7%, respectively; P=0.002). ConclusionsStatin therapy correlated with a lower rate of cardiovascular events in VSA patients free of significant organic stenosis. Statins seems to improve the prognosis of VSA patients free of significant organic stenosis.

Helicobacter pylori infection and interleukin-1 polymorphisms are associated with an increased risk of gastric cancer. We examined the prevalence of Helicobacter pylori seropositivity and interleukin-1 polymorphisms between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome patients.We recruited consecutive acute coronary syndrome patients, and 101 non-ST-segment elevation acute coronary syndrome patients and 103 ST-segment elevation myocardial infarction patients were enrolled. Interleukin-1 polymorphism analyses were performed for single nucleotide polymorphism in interleukin-1 beta-511 and the variable number of tandem repeats polymorphism in the interleukin-1 receptor antagonist by polymerase chain reaction. Immunoglobulin G antibodies against Helicobacter pylori and high sensitivity C-reactive protein were also measured.The rates of the simultaneous presence of interleukin-1 polymorphisms and Helicobacter pylori-seropositivity between non-ST-segment elevation acute coronary syndrome and ST-segment elevation myocardial infarction groups were 25.7% and 42.7%, respectively (P = 0.012). Helicobacter pylori-seropositive subjects with interleukin-1 polymorphisms showed significantly higher levels of high sensitivity C-reactive protein (0.04-0.12 vs. 0.02-0.05; P

BackgroundNon–vitamin K antagonist oral anticoagulants are used to prevent thromboembolism in patients with atrial fibrillation. The T‐TAS “Total Thrombus‐formation Analysis System” (Fujimori Kogyo Co Ltd) was developed for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, platelet chip [PL] ; collagen plus tissue factor, atheroma chip [AR]). We evaluated the utility of T‐TAS in predicting periprocedural bleeding in atrial fibrillation patients undergoing catheter ablation (CA). Methods and ResultsAfter exclusion of 20 from 148 consecutive patients undergoing CA, the remaining 128 patients were divided into 2 treatment groups: the warfarin group (n=30) and the non–vitamin K antagonist oral anticoagulants group (n=98). Blood samples obtained on the day of CA (anticoagulant‐free point) and at 3 and 30 days after CA were used in T‐TAS to compute the thrombus formation area under the curve (AUC; AUC for the first 10 minutes for PL tested at flow rate of 24 μL/min [PL24‐AUC10]; AUC for the first 30 minutes for AR tested at flow rate of 10 μL/min [AR10‐AUC30]). AR10‐AUC30 and PL24‐AUC10 levels were similar in the 2 groups on the day of CA. Levels of AR10‐AUC30, but not PL24‐AUC10, were significantly lower in the 2 groups at days 3 and 30 after CA. Multiple logistic regression analyses identified the AR10‐AUC30 level on the day of CA as a significant predictor of periprocedural bleeding events (odds ratio 5.7; 95% CI 1.54–21.1; P=0.009). Receiver operating characteristic analysis showed that the AR10‐AUC30 level on the day of CA significantly predicted periprocedural bleeding events (AUC 0.859, 95% CI 0.766–0.951; P

Background Myocardial lactate production in the coronary circulation during acetylcholine (ACh)‐provocation test (abbreviated as lactate production) provides supporting evidence for coronary spasm–induced myocardial ischemia. The purpose of this study was to examine the clinical features, predictive factors, and prognosis of patients with coronary vasospastic angina (VSA) and lactate production. Methods and Results We examined all 712 patients who underwent both myocardial lactate measurement during ACh‐provocation test in the left coronary artery and genetic screening test of a –786T/C polymorphism in the 5′‐flanking region of the endothelial nitric oxide synthase (eNOS) gene between January 1991 and December 2010. Lactate production was observed in 252 of the 712 patients and in 219 of 356 VSA patients diagnosed by ACh‐provocation test. Compared with lactate production–negative VSA patients, the lactate production–positive counterparts were more likely to be nonsmoker female diabetics with –786T/C eNOS polymorphism (61% vs 31%, P

This is a case report in which a 60-year-old man who suffered from ventricular tachycardia with dilated cardiomyopathy was prescribed amiodarone. After taking amiodarone, liver enzymes were increased and computed tomographic (CT) scanning of the abdomen showed a significant increase in the density of the liver without contrast medium. He was suspected as hemochromatosis and liver biopsy was performed. An abnormal high density of liver tissue may be observed in an unenhanced CT in patients treated with amiodarone and we suggest that periodic monitoring of liver function and/or liver biopsy is warranted before an irreversible stage is reached.