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Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it.Methods and Results: We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month follow-up (hazard ratio: 0.087, 95% confidence interval: 0.017-0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs.ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.

Aims Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). Methods and results Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced ( Conclusion This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.

The 4-Fr catheter system is not recommended for invasive functional assessment of coronary artery stenosis, because it tends to distort the aortic waveform. This study aimed to identify the incidence of aortic waveform distortion and a feasible method for correct diagnosis of coronary artery stenosis with a 4-Fr catheter. We retrospectively investigated 178 lesions with intermediate coronary artery stenosis. Non-hyperemic distal coronary artery pressure (Pd) and aortic pressure (Pa) were measured with a 4-Fr diagnostic or 6-Fr guiding catheter before and after saline flush. The mean Pd/mean Pa (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated before and after flushing. We compared the effect of flushing on the changes in Pd/Pa and iFR between the 4-Fr diagnostic and 6-Fr guiding catheters. Using the 4-Fr diagnostic catheter, there was a significant decrease in incidence of aortic waveform distortion from 42.0% (47 lesions) before flushing to 1.8% (2 lesions) after flushing (p

Previous studies have reported that high-dose strong statin therapy reduces the incidence of contrast-induced nephropathy (CIN) in statin naïve patients; however, the efficacy of high-dose strong statins for preventing CIN in real-world clinical practice remains unclear. The aim of this study was to evaluate the efficacy of strong statin therapy in addition to fluid hydration for preventing CIN after cardiovascular catheterization.Methods and Results: This prospective, multicenter, randomized controlled trial included 420 patients with chronic kidney disease who underwent cardiovascular catheterization. They were assigned to receive high-dose pitavastatin (4 mg/day × 4 days) on the day before and of the procedure and 2 days after the procedure (Statin group, n=213) or no pitavastatin (Control group, n=207). Isotonic saline hydration combined with a single bolus of sodium bicarbonate (20 mEq) was scheduled for administration to all patients. In the control group, statin therapy was continued at the same dose as that before randomization. CIN was defined as a ≥0.5 mg/dL increase in serum creatinine or ≥25% above baseline at 48 h after contrast exposure. Before randomization, 83% of study participants were receiving statin treatment. The statin group had a higher incidence of CIN than the control group (3.0% vs. 0%, P=0.01). The 12-month rate of major adverse cardiovascular events was similar between the 2 groups.High-dose pitavastatin increases the incidence of CIN in this study population.

BACKGROUND: The antitumor effect of statins has been highlighted, but clinical study results remain inconclusive. While patients with diabetes are at high risk of cancer, it is uncertain whether statins are effective for cancer chemoprevention in this population. OBJECTIVE: This study evaluated the association between statins and cancer incidence/mortality in patients with type 2 diabetes. DESIGN: This study was a follow-up observational study of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which was a randomized controlled trial of low-dose aspirin in Japanese patients with type 2 diabetes. PARTICIPANTS: This study enrolled 2536 patients with type 2 diabetes, age 30–85 years, and no history of atherosclerotic cardiovascular disease, from December 2002 until May 2005. All participants recruited in the JPAD trial were followed until the day of any fatal event or July 2015. We defined participants taking any statin at enrollment as the statin group (n = 650) and the remainder as the no-statin group (n = 1886). MAIN MEASURES: The primary end point was the first occurrence of any cancer (cancer incidence). The secondary end point was death from any cancer (cancer mortality). KEY RESULTS: During follow-up (median, 10.7 years), 318 participants developed a new cancer and 123 died as a result. Cancer incidence and mortality were 10.5 and 3.7 per 1000 person-years in the statin group, and 16.8 and 6.3 per 1000 person-years in the no-statin group, respectively. Statin use was associated with significantly reduced cancer incidence and mortality after adjustment for confounding factors (cancer incidence: adjusted hazard ratio [HR], 0.67; 95% CI, 0.49–0.90, P = 0.007; cancer mortality: adjusted HR, 0.60; 95% CI, 0.36–0.98, P = 0.04). CONCLUSIONS: Statin use was associated with a reduced incidence and mortality of cancer in Japanese patients with type 2 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06167-5) contains supplementary material, which is available to authorized users.

OBJECTIVE To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women. RESEARCH DESIGN AND METHODS This study is a follow-up cohort study of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial, which was a randomized, open-label, standard care–controlled trial examining the effects of low-dose aspirin on cardiovascular events. We followed up 2,536 Japanese patients with type 2 diabetes (T2D) enrolled in the JPAD trial from 2002 to 2017. The primary outcome of this post hoc analysis was the incidence of dementia, which was defined by the prescription of antidementia drugs or admission due to dementia. RESULTS Among the originally enrolled patients, 2,121 (84%) retained their original allocation. During a median follow-up of 11.4 years, 128 patients developed dementia. The overall effect of low-dose aspirin on the prevention of dementia adjusted for age, sex, and other established risk factors was not significant (hazard ratio [HR] 0.82, 95% CI 0.58–1.16). However, a significant reduction was seen in the risk of dementia in women (HR 0.58, 95% CI 0.36–0.95), but not in men (HR 1.27, 95% CI 0.75–2.13) (Pinteraction = 0.03). CONCLUSIONS Long-term use of low-dose aspirin may reduce the risk for dementia in women with T2D.

Percutaneous transluminal septal myocardial ablation (PTSMA) is an established procedure for treating symptomatic hypertrophic obstructive cardiomyopathy. We report a case of urgent PTSMA for treating refractory heart failure due to exacerbated obstruction of the left ventricular outflow tract after surgical aortic valvular replacement to treat severe aortic stenosis., Urgent percutaneous transluminal septal myocardial ablation might be a safe option for treating heart failure due to exacerbated left ventricular outflow tract obstruction after surgical aortic valvular replacement.

Background Silent events with newly developed Q waves in electrocardiogram (ECG) [silent myocardial infarction (MI)] in diabetic patients is reported to be independently associated with an increased risk of fatal MI. However, the incidence rate of silent MI in diabetic patients has yet to be clarified. We sought to determine the incidence rate of first symptomatic MI and silent MI in diabetic patients. Methods We conducted a prospective cohort study on patients enrolled in the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial which was started in 2002. It is a randomized controlled trial to examine the efficacy of low-dose aspirin therapy for the primary prevention of atherosclerotic events in type 2 diabetic patients. No patients had Q waves in their ECG before entry to the JPAD trial. We followed-up 1825 patients until July 2015 after completion of the JPAD trial in 2008. The median follow-up period was 10.3 years. We collected 1648 patients’ ECGs to identify patients with silent MI. Results Symptomatic MI occurred in 65 patients and silent MI occurred in 22 patients. The incidence rate of symptomatic MI was 4.26 per 1000 patient-years and 1.44 for silent MI in diabetic patients. Thus, 25% of total MIs were silent. Cause-specific Cox proportional hazard model indicated that age (hazard ratio 1.06, 95% confidence interval; 1.03–1.10, p = 0.0004) and long history of diabetes (1.00, 1.01–1.07, p = 0.01) were independently associated with symptomatic MI, but these were not associated with silent MI. Conclusions We demonstrated that incidence rate of first silent MI and that proportion of silent MI to all MIs was 25% in diabetic patients without a history of atherosclerotic events. Diabetic patients frequently need ECG screening for detection of silent MI.

IntroductionThe incidence of atrial fibrillation (AF), a significant risk factor for cardiovascular disease (CVD), is increasing worldwide. Type 2 diabetes mellitus (T2D) and advanced age are recognized as major risk factors for AF, but herein, we evaluated the incidence of AF in elderly patients with T2D and compared the prognosis between these patients with/without AF.Research design and methodsThe Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD2) study is a follow-up cohort study of the JPAD trial, a randomized controlled clinical trial initiated in 2002 in 2535 Japanese patients with T2D, to examine whether low-dose aspirin prevents CVD. After completion of that trial, we followed up the patients until 2019 and evaluated the incidence of AF. We also compared the incidence of cerebral cardiovascular events in elderly patients with T2D with/without AF.ResultsDuring the median follow-up period of 10.9 years, 132 patients developed AF (incidence rate: 5.14/1000 person-years). The adjusted HRs for cerebral cardiovascular events, stroke, coronary artery disease, heart failure, and all-cause death in elderly patients with T2D with versus without AF were 1.65 (95% CI 1.03 to 2.66), 1.54 (95% CI 0.81 to 2.93), 1.96 (95% CI 1.03 to 3.73), 5.17 (95% CI 2.46 to 10.89), and 1.82 (95% CI 1.24 to 2.67), respectively.ConclusionsAnnually, 1 in 200 elderly Japanese patients with T2D are estimated to develop AF. Because elderly patients with T2D with AF are at an elevated risk for CVD, careful follow-up of this patient subgroup is necessary.Trial registration numberNCT00110448.

The 4-Fr catheter system is not recommended for invasive functional assessment of coronary artery stenosis, because it tends to distort the aortic waveform. This study aimed to identify the incidence of aortic waveform distortion and a feasible method for correct diagnosis of coronary artery stenosis with a 4-Fr catheter. We retrospectively investigated 178 lesions with intermediate coronary artery stenosis. Non-hyperemic distal coronary artery pressure (Pd) and aortic pressure (Pa) were measured with a 4-Fr diagnostic or 6-Fr guiding catheter before and after saline flush. The mean Pd/mean Pa (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated before and after flushing. We compared the effect of flushing on the changes in Pd/Pa and iFR between the 4-Fr diagnostic and 6-Fr guiding catheters. Using the 4-Fr diagnostic catheter, there was a significant decrease in incidence of aortic waveform distortion from 42.0% (47 lesions) before flushing to 1.8% (2 lesions) after flushing (p 0.001); the incidence was only 3.0% before saline flush and decreased to 0% after saline flush when using the 6-Fr guiding catheter. The presence of aortic waveform distortion influenced the iFR when the 4-Fr system was used. Functional measurements with the 4-Fr diagnostic catheter require adequate saline flush to remove the influence of aortic waveform distortion.

OBJECTIVE This study analyzed the efficacy of low-dose aspirin in cancer chemoprevention in patients with diabetes. RESEARCH DESIGN AND METHODS This study was a posttrial follow-up of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial. Participants in the JPAD trial (2,536 Japanese patients with type 2 diabetes and without preexisting cardiovascular disease) were randomly allocated to receive aspirin (81 or 100 mg daily) or no aspirin. After that trial ended in 2008, we followed up with the participants until 2015, with no attempt to change the previously assigned therapy. The primary end point was total cancer incidence. We investigated the effect of low-dose aspirin on cancer incidence. RESULTS During the median follow-up period of 10.7 years, a total of 318 cancers occurred. The cancer incidence was not significantly different between the aspirin and no-aspirin groups (log-rank, P = 0.4; hazard ratio [HR], 0.92; 95% CI, 0.73–1.14; P = 0.4). In subgroup analyses, aspirin did not affect cancer incidence in men, women, or participants aged ≥65 years. However, it decreased cancer incidence in participants aged CONCLUSIONS Low-dose aspirin did not reduce cancer incidence in Japanese patients with type 2 diabetes.

Objectives The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. Background The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. Methods The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. Results NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of −2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). Conclusions Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227)

Background: The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. Methods: The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard care–controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity. Results: The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91–1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83–1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction P >0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82–1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group ( P =0.03), and the incidence of hemorrhagic stroke was not different between groups. Conclusions: Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00110448.

Introduction The presence of atrial fibrillation (AF) in patients with reduced left ventricular ejection fraction (LVEF) is associated with increased risks of mortality and hospitalization for heart failure (HF). Although prior studies reported that catheter ablation (CA) for AF in low LVEF patients reduced risks of all-cause mortality and HF hospitalization, the predictors of worsening HF after ablation has not been adequately evaluated. Purpose The purpose of this study was to investigate the impact of improvement in LVEF after AF ablation on the incidence of subsequent HF hospitalization in patients with low LVEF. Methods The Kansai Plus Atrial Fibrillation (KPAF) Registry is a multicenter registry enrolling 5,013 consecutive patients undergoing first-time ablation for AF. The current study population consisted of 1,031 patients with reduced LVEF of Results During the median follow-up of 1067 [879–1226] days, patients improved LVEF had lower rate of HF hospitalization, compared with those with unchanged and worsened LVEF (2.1%, 8.0%, and 21.5%, respectively, P Figure 1 Conclusion Among patients with reduced LVEF undergoing AF ablation, patients with subsequently improved LVEF in association with maintained sinus rhythm had markedly lower risk of HF hospitalization during follow-up as compared with those with unchanged or worsened LVEF.

Background and purposeThere are few data that demonstrate a significant effect of aspirin therapy for diabetic patients as primary prevention for cardiovascular events. A guideline recommends the use of aspirin as a primary prevention strategy in patients with diabetes who are at increased cardiovascular risk including those who have additional risk factors. To clarify the effect of primary prevention with aspirin therapy on diabetic patients, the relationship between C-reactive protein (CRP) and the incidence of atherosclerotic events was investigated in participants in the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial.Methods and subjectsWe divided the JPAD participants according to the CRP level at enrollment; CRP≥0.1mg/dl: high CRP group, CRP

Background Excimer laser coronary atherectomy (ELCA) recently became available in Japan, but ELCA's effectiveness and safety are not clear. Methods and results We enrolled consecutive patients who underwent ELCA and were registered in the U tility of L aser for Tr anscatheter A therectomy— M ulticenter A nalysis around N aniwa (ULTRAMAN) registry comprising six Japanese medical centers around Naniwa in Japan with patients registered from April 2006 to June 2015. We evaluated the catheter sizes used and compared the success rate, thrombolysis in myocardial infarction (TIMI) flow, blush score, and complications between the rich-thrombus (RT) group [acute coronary syndrome (ACS) and saphenous vein graft (SVG)] and the poor-thrombus (PT) group [in-stent restenosis (ISR), chronic total occlusion (CTO), calcification, and long or bifurcation (L&B) lesions]. Of the 328 patients, 6 (1.8%) were treated for an SVG, 175 (53.4%) were treated for ACS, 18 (5.5%) for CTO, 106 (32.4%) for ISR, 8 (2.4%) for calcification, and 15 for L&B lesions (4.6%). A 1.7-mm (concentric)-diameter ELCA catheter was used most frequently (59.4%). High success rates were achieved in both the RT and PT groups, but the TIMI flow grade and blush score were significantly lower and the complications rate was significantly higher in the RT group ( n = 181). Conclusions In Japan, the major indications for ELCA have been ACS and ISR. ELCA can provide a safe and effective treatment even for RT lesions.

OBJECTIVE Recent reports showed that low-dose aspirin was ineffective in the primary prevention of cardiovascular events in diabetic patients overall. We hypothesized that low-dose aspirin would be beneficial in patients receiving insulin therapy, as a high-risk group. RESEARCH DESIGN AND METHODS This study is a subanalysis of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial—a randomized, controlled, open-label trial. We randomly assigned 2,539 patients with type 2 diabetes and no previous cardiovascular disease to the low-dose aspirin group (81 or 100 mg daily) or to the no-aspirin group. The median follow-up period was 4.4 years. We investigated the effect of low-dose aspirin on preventing atherosclerotic events in groups receiving different diabetes management. RESULTS At baseline, 326 patients were treated with insulin, 1,750 with oral hypoglycemic agents (OHAs), and 463 with diet alone. The insulin group had the longest history of diabetes, the worst glycemic control, and the highest prevalence of diabetic microangiopathies. The diet-alone group had the opposite characteristics. The incidence of atherosclerotic events was 26.6, 14.6, and 10.4 cases per 1,000 person-years in the insulin, OHA, and diet-alone groups, respectively. In the insulin and OHA groups, low-dose aspirin did not affect atherosclerotic events (insulin: hazard ratio [HR] 1.19 [95% CI 0.60−2.40]; OHA: HR 0.84 [0.57−1.24]). In the diet-alone group, low-dose aspirin significantly reduced atherosclerotic events, despite the lowest event rates (HR 0.21 [0.05−0.64]). CONCLUSIONS Low-dose aspirin reduced atherosclerotic events predominantly in the diet-alone group and not in the insulin or OHA groups.

OBJECTIVE Type 2 diabetes accompanied by renal damage is a strong risk factor for atherosclerotic events. The purpose of this study was to investigate the efficacy of low-dose aspirin therapy on primary prevention of atherosclerotic events in patients with type 2 diabetes and coexisting renal dysfunction. RESEARCH DESIGN AND METHODS The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial was a prospective, randomized, open-label trial conducted throughout Japan that enrolled 2,539 type 2 diabetic patients without a history of atherosclerotic diseases. Patients were assigned to the aspirin group (81 mg/day or 100 mg/day) or the nonaspirin group and followed for a median of 4.37 years. The primary end points were atherosclerotic events of fatal and nonfatal ischemic heart disease, stroke, and peripheral arterial disease. RESULTS The analysis included 2,523 patients who had serum creatinine measured. In 1,373 patients with baseline estimated glomerular filtration rate (eGFR) 60–89 mL/min/1.73 m2, the incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group (aspirin, 30/661; nonaspirin, 55/712; hazard ratio 0.57 [95% CI 0.36–0.88]; P = 0.011). Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥90 mL/min/1.73 m2 (aspirin, 9/248; nonaspirin, 11/270; 0.94 [0.38–2.3]) or those with eGFR CONCLUSIONS These results suggest a differential effect of low-dose aspirin therapy in diabetic patients with eGFR 60–89 mL/min/1.73 m2.

Background: In 2013, the blood pressure (BP) control target for diabetic patients was changed in both Europe and USA; however, there was a paucity of supporting evidence. We investigated whether BP control Methods: We performed the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial to examine the efficacy of low-dose aspirin therapy in 2536 type 2 diabetes patients. After completion of the JPAD trial in 2008, we followed up the same subjects until 2013, the JPAD2 cohort. Primary end points were a composite of ischemic heart disease, stroke, peripheral arterial disease, and sudden death. We divided the patients into either a high age 65 (H65) group (n=1360; age≥65 years) or a low age 65 (L65) group (n=1176; age Results: Systolic BP was unchanged 131 mmHg in 2009 and 130 mmHg in 2013 in each JPAD patients. Diastolic BP decreased from 73 mmHg in 2009 to 71 mmHg in 2013. The difference of incidence of atherosclerotic events between BP≥140/90 patients and BP Conclusions: The difference of incidence of atherosclerotic events between BP≥140/90 patients and BP

2015 AHA Effectiveness of Ethanol Infusion in the Vein of Marshall for Bidirectional Mitral Isthmus Block in Unsuccessful Cases with Conventional Ablation [Introduction] Treatment of mitral isthmus dependent atrial tachycardia (AT) requires bidirectional mitral isthmus (MI) block. It is usually difficult to achieve bidirectional MI block by endocardial linear ablation. When MI block is incomplete, additional ablation inside the coronary sinus (CS) is often required. The vein of Marshall (VOM) is located in the epicardial aspect of MI. The purpose of this study is to determine whether complete bidirectional MI block is obtained by ethanol infusion in the VOM in cases with incomplete MI block by conventional ablation. [Method] This study consisted of 38 consecutive patients who underwent conventional ablation to obtain bidirectional MI block from October 2013 to September 2014. [Results] In 24 patients (63%), bidirectional MI block was achieved by conventional ablation. In 11 patients (29%) of the other 14 patients, the CS venogram was performed to assess the presence or absence of the VOM. The VOM was imaged in 9 patients (24%), into which 100% ethanol was injected (2ml, 2-3times). After ethanol infusion in the VOM, bidirectional MI block was obtained in all cases (Figure). [Conclusion] Ethanol infusion in the VOM is an effective treatment in cases with incomplete MI block by conventional ablation.

Objectives Our aim was to investigate cardiac expression of placental growth factor (PlGF) and its clinical significance in patients with acute myocardial infarction (AMI). Background Placental growth factor is known to stimulate wound healing by activating mononuclear cells and inducing angiogenesis. The clinical significance of PlGF in AMI is not yet known. Methods Fifty-five AMI patients and 43 control subjects participated in the study. Peripheral blood sampling was performed on days 1, 3, and 7 after AMI. Blood was also sampled from the coronary artery (CAos) and the coronary sinus (CS), before and after acute coronary recanalization. Cardiac expression of PlGF was analyzed in a mouse AMI model. Results In AMI patients, peripheral plasma PlGF levels on day 3 were significantly higher than in control subjects. Plasma PlGF levels just after recanalization were significantly higher in the CS than the CAos, which indicates cardiac production and release of PlGF. Peripheral plasma levels of PlGF on day 3 were negatively correlated with the acute phase left ventricular ejection fraction (LVEF), positively correlated with both acute phase peak peripheral monocyte counts and chronic phase changes in LVEF. Placental growth factor messenger ribonucleic acid expression was 26.6-fold greater in a mouse AMI model than in sham-operated mice, and PlGF was expressed mainly in endothelial cells within the infarct region. Conclusions Placental growth factor is rapidly produced in infarct myocardium, especially by endothelial cells during the acute phase of myocardial infarction. Placental growth factor might be over-expressed to compensate the acute ischemic damage, and appears to then act to improve LVEF during the chronic phase.

Introduction: It has been reported that dipeptidyl peptidase (DPP) IV inhibitor treatment increased glucagon like peptide (GLP)-1 and GLP-1 receptor expression levels, and subsequently endothelial nitric oxide synthase levels in experimental studies. It is possible that DPP IV inhibitors modify blood pressure (BP) through the improvement of endothelial function. Hypothesis: The aim of this study was to investigate whether DPP IV inhibitors ameliorated BP in diabetic patients. Methods: The JPAD trial, 2002 to 2008, a multicenter, prospective, randomized, open label, blinded, end-point study, was undertaken to examine the efficacy of aspirin therapy. After completion of the trial in 2008, we followed the same subjects until 2013 as JPAD2 trial cohort. BP was measured in 1244 patients in both 2009 and 2013. Among the 1244 patients, 4 patients received DPPIV inhibitors in 2009, 280 patients in 2011, 573 patients in 2013. We examined the change of BP in the 573 patients. Among them, 344 patients had systolic BP≥140 mmHg or diastolic BP≥90 mmHg or both (high BP group). Results: The systolic BP from 2009 to 2013 did not significantly change in the 1244 patients (Figure). The diastolic BP significantly decreased in the 1244 patients (Figure). The systolic BP from 2009 to 2013 did not significantly change in the 573 patients receiving DPPIV inhibitors (Figure). The diastolic BP significantly decreased in the 573 patients receiving DPPIV inhibitors (Figure). In the high BP group, the systolic BP from 2009 to 2013 significantly decreased in the 148 patients receiving DPPIV inhibitors (Figure). In the high BP group, the diastolic BP significantly decreased in the 148 patients receiving DPPIV inhibitors (Figure). Conclusions: In 4 year-observation of the JPAD2 trial cohort, diastolic BP decreased and systolic BP did not change in diabetic patients. User of DPPIV inhibitors has been dramatically increased, and it significantly modifies systolic BP in high BP diabetic patients.

We report a case of stunned myocardium induced by coronary vasospasm which was associated with spontaneous pneumothorax. A 72-year-old woman with a sudden onset of chest pain was transferred to our hospital by an ambulance. Electrocardiography on admission suggested evidence of myocardial ischemia, and chest radiography disclosed a right pneumothorax. After right chest drainage was carried out, the findings of myocardial ischemia on electrocardiography persisted. Therefore, emergency coronary angiography was performed, which demonstrated coronary vasospasm on an acetylcholine loading test. Left ventriculography revealed akinesis in a portion of the anterior wall that normalized on echocardiography two days later. We made a diagnosis of stunned myocardium associated with pneumothorax. The severe chest pain and respiratory alkalosis were conseqences of the coronary vasospasm. It is known that the electrocardiographic characteristics of pneumothorax are similar to those of myocardial ischemia. In patients with pneumothorax and ST-T changes on electrocardiography, coronary vasospasm should be considered.

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.

急性下壁梗塞患者での退院時運動負荷心電図所見は, 胸部誘導にST低下を示す偽陽性例の頻度が高い.そこで著者らは, ST低下が出現する誘導から冠動脈狭窄を予測できるか, さらに運動負荷時胸部誘導でのST低下の機序について検討した.急性期の経皮的冠動脈形成術により有意の冠動脈狭窄を有さない27例をI群, いすれかの冠動脈に有意狭窄を有する18例をII群とした.胸部誘導でのST低下はI群で症例の37.0%, II群で83.3%に認められた.胸部誘導のST低下を示した症例の中で肢誘導のST低下を伴うものは, II群がI群に比して有意に高率であった (86.7%vs20.0%, p

Background: Benefit of low-dose aspirin for primary prevention of cardiovascular events in diabetes remains controversial. The American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients: older patients with additional cardiovascular risk factors. We evaluated aspirin’s benefit in Japanese diabetic patients stratified by cardiovascular risk. Methods and Results: In the JPAD trial, we enrolled 2,539 Japanese patients with type 2 diabetes and no history of cardiovascular disease. We randomly assigned them to aspirin (81–100mg daily) or no aspirin groups. The median follow-up period was 4.4 years. We stratified the patients into high-risk or low-risk groups, according to the US recommendation: age (older; younger) and coexisting cardiovascular risk factors. The risk factors included smoking, hypertension, dyslipidemia, family history of coronary artery disease, and proteinuria. Most of the patients were classified into the high-risk group, consisting of older patients with risk factors (n=1,804). The incidence of cardiovascular events was higher in this group, but aspirin did not reduce cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]: 0.58–1.17). In the low-risk group, consisting of older patients without risk factors and younger patients (n=728), aspirin did not reduce cardiovascular events (HR, 0.55; 95% CI: 0.23–1.21). These results were unchanged after adjusting for potential confounding factors. Conclusions: Low-dose aspirin is not beneficial in Japanese diabetic patients at high risk. (Circ J 2013; 77: 3023–3028)

Background: There are few data that demonstrate a significant effect of aspirin therapy for diabetic patients. To clarify the effect of the primary prevention of aspirin therapy in diabetic patients, the relationship between blood pressure (BP) and the incidence of atherosclerotic events was investigated in participants in the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial. Methods and Results: We divided the JPAD participants according to their systolic (SBP) and diastolic (DBP) BPs at enrollment (SBP ≥140mmHg and/or DBP ≥90mmHg: unattained group, SBP

OBJECTIVE Type 2 diabetes accompanied by renal damage is a strong risk factor for atherosclerotic events. The purpose of this study was to investigate the efficacy of low-dose aspirin therapy on primary prevention of atherosclerotic events in patients with type 2 diabetes and coexisting renal dysfunction. RESEARCH DESIGN AND METHODS The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial was a prospective, randomized, open-label trial conducted throughout Japan that enrolled 2,539 type 2 diabetic patients without a history of atherosclerotic diseases. Patients were assigned to the aspirin group (81 mg/day or 100 mg/day) or the nonaspirin group and followed for a median of 4.37 years. The primary end points were atherosclerotic events of fatal and nonfatal ischemic heart disease, stroke, and peripheral arterial disease. RESULTS The analysis included 2,523 patients who had serum creatinine measured. In 1,373 patients with baseline estimated glomerular filtration rate (eGFR) 60–89 mL/min/1.73 m2, the incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group (aspirin, 30/661; nonaspirin, 55/712; hazard ratio 0.57 [95% CI 0.36–0.88]; P = 0.011). Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥90 mL/min/1.73 m2 (aspirin, 9/248; nonaspirin, 11/270; 0.94 [0.38–2.3]) or those with eGFR

Previous trials have investigated the effects of low-dose aspirin on primary prevention of cardiovascular events, but not in patients with type 2 diabetes.To examine the efficacy of low-dose aspirin for the primary prevention of atherosclerotic events in patients with type 2 diabetes.Multicenter, prospective, randomized, open-label, blinded, end-point trial conducted from December 2002 through April 2008 at 163 institutions throughout Japan, which enrolled 2539 patients with type 2 diabetes without a history of atherosclerotic disease and had a median follow-up of 4.37 years.Patients were assigned to the low-dose aspirin group (81 or 100 mg per day) or the nonaspirin group.Primary end points were atherosclerotic events, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease. Secondary end points included each primary end point and combinations of primary end points as well as death from any cause.A total of 154 atherosclerotic events occurred: 68 in the aspirin group (13.6 per 1000 person-years) and 86 in the nonaspirin group (17.0 per 1000 person-years) (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; log-rank test, P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01-0.79; P = .0037). A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57-1.14; log-rank test, P = .67). The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups.In this study of patients with type 2 diabetes, low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events.clinicaltrials.gov Identifier: NCT00110448.

A 76-year-old woman was admitted with a one-month history of low grade fever and dizziness. She had a palpable right supraclavicular lymph node. Abdominal ultrasonography showed swollen lymph nodes around the abdominal aorta. A specimen from the right supraclavicular lymph node showed malignant lymphoma (diffuse large B cell type). We started chemotherapy according to the low-dose THP-COP protocol (pirarubicin, cyclophosphamide, vincristine and prednisolone) on the 31st hospital day. Since no adverse effects were detected after two low-dose cycles, the patient received a third course with standard doses on the 87th hospital day. The total dose of pirarubicin was 72 mg/m2. Two days after the third course started, she suffered from dyspnea caused by congestive heart failure. A chest X-ray showed advanced cardiomegaly, severe congestion and bilateral pleural effusion. These conditions improved with transvenous administration of diuretics, a vasodilator and phosphodiesterase inhibitor. In this case, congestive heart failure developed even though the total dose of pirarubicin was lower than in previous reports of this complication. When the THP-COP protocol is indicated in elderly patients, cardiotoxicity should be monitored even if the total dose of pirarubicin is very low.

QT dispersion has been recognized as an undesirable marker because of its association with arrhythmogenicity in patients with myocardial infarction, but the relation between QT interval dispersion and wall motion abnormalities has not been clarified. After the introduction of reperfusion therapy, it was recognized that T waves were inverted twice in the course of myocardial infarction. An investigation was made of the clinical significance of QT dispersion in relation to the presence of inverted T waves and left ventricular wall motion abnormalities in 34 patients (mean age, 59 years) with acute anterior myocardial infarction who underwent successful reperfusion therapy. The amplitude of the deepest inverted T waves occurring within the first 3 days (T1) and after 3 days (T2) of myocardial infarction were measured in electrocardiographic (ECG) lead V3. On the ECGs on which T1 and T2 were recorded, QT dispersion was calculated (QTd1, QTd2), and T1 and T2 were correlated with QTd1 (r = .65) and QTd2 (r = .47), respectively. The difference between the extent of asynergy in the acute phase and the chronic phase, which was evaluated by the centerline method, was correlated with T1 (r = .63) and QTd1 (r = .67). Patients with a QTd1 of 0.1 second or longer showed a greater change in the extent of asynergy (23.4 +/- 13.1% vs 4.9 +/- 9.8%, P < .01) and less asynergy in the chronic phase (19.9 +/- 15.6% vs 46.5 +/- 14.0%, P < .01) than patients with a QTd1 of less than 0.1 second. Thus, QT dispersion in the acute phase of anterior myocardial infarction indicates recovery of left ventricular wall motion. Prolongation of the local action potential duration of the myocardium that recovers from severe ischemia may be a contributor to the increased QT dispersion that results in inversion of T waves in the acute phase of myocardial infarction.

Objective: To investigate plasma concentrations of adrenomedullin in patients with septic shock and the potential association of these concentrations with relaxation of vascular tone. Design: Prospective, case series. Setting: Department of Emergency and Critical Care Medicine, Nara Medical University. Patients: Twelve patients who fulfilled the clinical criteria for severe sepsis or septic shock (as defined by the Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee) and 13 healthy volunteers. Interventions: Arterial blood samples were obtained via a 20-gauge cannula inserted into each patient's radial artery. Measurements and Main Results: After extraction and purification, plasma adrenomedullin was measured by radioimmunoassay. Systemic vascular resistance index, pulmonary vascular resistance, cardiac index, and stroke volume index were determined with a thermodilution catheter. The mean plasma concentration of adrenomedullin was markedly higher in patients than in controls (226.1 ± 66.4 [SEM] vs. 5.05 ± 0.21 fmol/mL, p

Purpose: Optimal coherence tomography (OCT) is an intravascular imaging modality to assess plaque characteristics. The aim of this study is to evaluate surface and inside of vulnerable plaques in carotid stenotic lesions which are detected as high-intensity area in T1-weighted-image by MRI (Black blood method), using OCT compared with VH-IVUS before carotid artery stenting (CAS). Methods: We performed CAS in consecutive 15 patients (mean age of 76±5 years) with carotid artery stenotic lesions in which MRI (T1-weighted image by Black blood method) detected the plaque as high intensity area. It has been reported that plaques which is detected as high-intensity area in T1-weighted image of black blood-MRI are considered most vulnerable plaques. Vulnerable plaque detected by MRI were evaluated by OCT and VH-IVUS before performing CAS. Before stenting, we assessed plaque at the stenotic lesions by frequency-domain OCT (Ilumien OCT imaging system) and by VH-IVUS (Eagle Eye) which classified plaque into four color components: fibrous, fibro-fatty, calcium and necrotic core. During OCT-image acquisition carotid blood flow was replaced by dextran or contrast medium injection from the guiding catheter at 5-6 mL/sec with an injector pump. In analyzing OCT images, lipid rich plaque was defined as signal intensity-poor lesion covered by signal-rich bands that correspond to fibrous cap. Thin-cap fibroatheroma (TCFA) was defined as

Context Previous trials have investigated the effects of low-dose aspirin on primary prevention of cardiovascular events, but not in patients with type 2 diabetes. Objective To examine the efficacy of low-dose aspirin for the primary prevention of atherosclerotic events in patients with type 2 diabetes. Design, Setting, and Participants Multicenter, prospective, randomized, open-label, blinded, end-point trial conducted from December 2002 through April 2008 at 163 institutions throughout Japan, which enrolled 2539 patients with type 2 diabetes without a history of atherosclerotic disease and had a median follow-up of 4.37 years. Interventions Patients were assigned to the low-dose aspirin group (81 or 100 mg per day) or the nonaspirin group. Main Outcome Measures Primary end points were atherosclerotic events, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease. Secondary end points included each primary end point and combinations of primary end points as well as death from any cause. Results A total of 154 atherosclerotic events occurred: 68 in the aspirin group (13.6 per 1000 person-years) and 86 in the nonaspirin group (17.0 per 1000 person-years) (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; log-rank test, P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01-0.79; P = .0037). A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57-1.14; log-rank test, P = .67). The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups. Conclusion In this study of patients with type 2 diabetes, low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events. Trial Registration clinicaltrials.gov Identifier: NCT00110448Published online November 9, 2008 (doi: 10.1001/jama.2008.623).