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Background— Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized. Methods and Results— We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95–1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS 2 score of 0 or 1. When those patients were reevaluated using CHA 2 DS 2 -VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score–matched cohorts (n=45 each), Kaplan–Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13–76.5; P Conclusions— Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.

Background Coronary high-intensity plaques detected by noncontrast T1-weighted imaging may represent plaque instability. High-intensity plaques can be quantitatively assessed by a plaque-to-myocardium signal-intensity ratio (PMR). Objectives This pilot, hypothesis-generating study sought to investigate whether intensive statin therapy would lower PMR. Methods Prospective serial noncontrast T1-weighted magnetic resonance imaging and computed tomography angiography were performed in 48 patients with coronary artery disease at baseline and after 12 months of intensive pitavastatin treatment with a target low-density lipoprotein cholesterol level Results In the statin group, 12 months of statin therapy significantly improved low-density lipoprotein cholesterol levels (125 to 70 mg/dl; p Conclusions Statin treatment significantly reduced the PMR of high-intensity plaques. Noncontrast T1-weighted magnetic resonance imaging could become a useful technique for repeated quantitative assessment of plaque composition. (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique [AQUAMARINE]; UMIN000003567 )

An 85-year-old man was hospitalized because of ST-segment–elevation myocardial infarction 145 months after the implantation of sirolimus-eluting Cypher stent. Emergent coronary angiography identified in-stent restenosis at the body of sirolimus-eluting Cypher stent in the proximal right coronary artery (Figure [A]). Optical coherence tomography visualized rupture of lipidic neointima potentially containing cholesterol crystals (Figure [B]). Near-infrared spectroscopy (NIRS) combined with intravascular ultrasound showed extensive yellow signals indicating lipid accumulation, potentially both within and outside the stent, with a high, maximum 4-mm lipid core burden index with 880 (Figure [C] and [D]). After an implantation of cobalt–chromium everolimus-eluting stent, no-reflow phenomenon with thrombolysis in …

Background and Purpose— The incidence of heart failure increases the subsequent risk of ischemic stroke, and its risk could be higher in the short-term period after an acute heart failure (AHF) event. However, its determinants remain to be clarified. Plasma D-dimer level reflects fibrin turnover and exhibits unique properties as a biomarker of thrombosis. The aim of this study is to investigate whether D-dimer level is a determinant of short-term incidence of ischemic stroke in patients with AHF. Methods— We examined 721 consecutive hospitalized AHF patients with plasma D-dimer level on admission from our prospective registry between January 2013 and May 2016. The study end points were incidence of ischemic stroke during hospitalization and at 30 days after admission. Results— Of the total participants (mean age, 76 years; male, 60%; atrial fibrillation, 54%; mean left ventricular ejection fraction, 38%), in-hospital ischemic stroke occurred in 18 patients (2.5%) during a median hospitalization period of 21 days, and 30-day ischemic stroke occurred in 16 patients (2.2%). Higher D-dimer level on admission was an independent determinant of subsequent risk of in-hospital ischemic stroke even after adjustment by CHA 2 DS 2 -VASc score (odds ratio, 2.29; 95% confidence interval, 1.46–3.60; P P P =0.002) and those without antithrombotic therapy (odds ratio, 2.79; 95% confidence interval, 1.53–5.57; P Conclusions— Elevated plasma D-dimer level on admission was significantly associated with increased incidence of ischemic stroke shortly after admission for AHF, suggesting a predictive role of D-dimer for short-term ischemic stroke events in patients with AHF. Clinical Trial Registration— URL: https://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000017024.

Although current guidelines have highlighted the importance of evidence-based optimal medical therapy (OMT) in patients with previous coronary artery bypass grafting (CABG), the effect of OMT on post-CABG patients requiring secondary coronary revascularization on prognosis remains unknown. We sought to examine the impact of OMT on post-CABG patients who underwent percutaneous coronary intervention (PCI) as secondary revascularization. A total of 632 consecutive post-CABG patients who underwent PCI between 2001 and 2013 at our hospital (84% men, median age 71 years) were divided into 2 groups: patients who were discharged with OMT and patients who were discharged without OMT (non-OMT). OMT was defined as the combination of an antiplatelet agent, statin, β blocker, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Despite having a higher prevalence of clinical comorbidities, patients with OMT (n = 163) had a lower prevalence of all-cause death than those without OMT (n = 469) during a median follow-up of 95 months (OMT group 21.5%, non-OMT group 34.1%, p = 0.002). Both groups had similar procedural success rates. In a propensity-matched cohort (n = 146 each), OMT was associated with lower rates of all-cause death and cardiac death than non-OMT 8 years after PCI. In multivariable analysis, OMT was an independent predictor of all-cause death (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.34 to 0.72, p 0.001). In conclusion, OMT plays a protective role and reduces all-cause death in post-CABG patients requiring subsequent PCI. Outside of the domain of coronary revascularization, OMT could be considered an essential treatment in this patient population.

Despite current therapies, acute heart failure (AHF) remains a major public health burden with high rates of in-hospital and post-discharge morbidity and mortality. Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide that promotes vasodilation with increased salt and water excretion, which leads to reduction of cardiac filling pressures. A previous open-label randomized controlled study showed that carperitide improved long-term cardiovascular mortality and heart failure (HF) hospitalization for patients with AHF, when adding to standard therapy. However, the study was underpowered to detect a difference in mortality because of the small sample size. Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF) is a multicenter, randomized, open-label, controlled study designed to evaluate the efficacy of intravenous carperitide in hospitalized patients with AHF. Patients hospitalized for AHF will be randomly assigned to receive either intravenous carperitide (0.02 μg/kg/min) in addition to standard treatment or matching standard treatment for 72 h. The primary end point is death or rehospitalization for HF within 2 years. A total of 260 patients will be enrolled between 2013 and 2018. The design of LASCAR-AHF will provide data of whether carperitide reduces the risk of mortality and rehospitalization for HF in selected patients with AHF.

Iron deficiency (ID) is commonly observed in chronic heart failure (HF) patients and is associated with worse clinical outcomes. While ID is frequent finding in hospitalized heart failure (HHF), its impact on long-term outcome in HHF patients remains unclear.We evaluated iron status at discharge in 578 HHF patients. Absolute ID was defined as serum ferritin100 μg/L, and functional ID (FID) was defined as serum ferritin of 100-299 μg/L with transferrin saturation20%. The primary outcome of interest was the composite of all-cause mortality and HF admission at one year.Among the study population, 185 had absolute ID, 88 had FID and 305 had no evidence of ID. At one-year post-discharge, 64 patients had died and 112 had been readmitted with HF. Patients with absolute ID had more adverse events than those with FID or no ID (p = 0.021). In multivariate Cox regression analyses, absolute ID was significantly associated with increased risk of adverse events at one year (HR 1.50, 95% CI 1.02-2.21, p = 0.040) compared with the remaining patients. Sensitivity analysis revealed that its prognostic effect did not differ across anemic status, or between HF with reduced and preserved ejection fraction (p for interaction = 0.17, 0.68, respectively).Absolute ID, but not FID, at discharge was associated with increased risk of one-year mortality or HF admission in patients with HHF. Further studies are required to evaluate the role of repleting iron stores and its impact on clinical outcomes in patients with HHF.

Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p 0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41; HR 1.76, 95% CI 1.10 to 2.82; HR 1.46, 95% CI 1.12 to 1.91, respectively; p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.

We retrospectively evaluated graft patency in patients who underwent no-touch aortic arterial off-pump coronary artery bypass grafting to determine the optimal selection of target vessels for improved graft patency of composite and sequential radial artery I-grafts.The radial artery was anastomosed to the end of an in situ internal thoracic artery and was sequentially anastomosed to non-left anterior descending arteries. This composite graft was defined as an "I-graft." We evaluated 145 I-grafts with 2, 3, or 4 sequential anastomoses (437 graft segments). A graft segment with the final distal anastomosis of every I-graft was defined as the last graft segment (LGS). When a sequential anastomosis was initiated from the left coronary branch, the I-graft assumed a clockwise course (69.0%). When a sequential anastomosis was initiated from the right coronary branch, the I-graft assumed a counterclockwise course (31.0%).On multivariable analysis, right coronary branch (P 0.001), moderately stenotic (50-75%) target vessel (P = 0.004), and LGS with moderately stenotic target vessel (P = 0.005) were predictors of mid-term graft occlusion. In situations where the LGS was anastomosed to a severely stenotic target vessel (75%) with a clockwise course, when the number of moderately stenotic target vessels among sequential graft segments was 0, 1, or ≥2, the mid-term graft patency rates of I-grafts were 94.0%, 86.0%, and 81.4%, respectively.The selection of target vessels for severely stenotic lesions among sequential graft segments and the clockwise course enhance the mid-term graft patency of sequential radial I-grafts.

Atherosclerotic cardiovascular disease (ASCVD) has become a major health burden and is expected to further increase in the future. Better predictive approaches for ASCVD and more efficacious therapies are required to further improve cardiovascular outcomes. Intravascular imaging has contributed to the elucidation of atherosclerotic mechanisms and evaluation of novel therapies. Near-infrared spectroscopy has enabled the visualization of the lipid extent of atherosclerotic plaques in vivo. Given that lipid accumulation is considered to promote the formation and progression of atherosclerosis, this technology may harbor the potential to identify subjects with high cardiovascular risks and thus adopt more optimized therapeutic approaches. Areas covered: This review will outline the characteristics of NIRS, its validation data and in vivo findings of NIRS imaging in patients with coronary artery disease. The comparisons of NIRS with other imaging modalities will reveal the distinct capability of NIRS imaging to monitor high-risk atheroma harboring lipidic composition. Furthermore, the predictive ability of NIRS-derived measures in the occurrence of ASCVD will be summarized. Expert commentary: Ex vivo and in vivo findings suggest NIRS imaging as a potential tool for cardiovascular risk assessment and monitoring the benefit of pharmacological approaches.

Aims Coronary high-intensity plaques (HIPs) with a high plaque-to-myocardial signal intensity ratio (PMR) on non-contrast T1-weighted imaging in patients with stable coronary artery disease (CAD) are associated with future coronary events. To characterize the morphological substrate of HIP, we performed a correlative optical coherence tomography (OCT) study. Methods and results We examined 137 lesions in 105 patients with stable angina pectoris or silent myocardial ischaemia scheduled for percutaneous coronary intervention (PCI) using a 3 T magnetic resonance scanner. Pre-interventional OCT was performed for PCI target lesions. HIP was defined as PMR ≥ 1.4. Of the 137 lesions, 34% were HIP and 66% were non-HIP. The prevalence of lipid-rich plaque (96% vs. 70%, P

Lower urinary sodium concentration (UNa) may reflect impaired renal perfusion, higher neurohormonal activity and diuretic resistance. However, the prognostic impact of UNa in patients with acute heart failure (AHF) has not been fully elucidated.We investigate the association between UNa and clinical outcomes in 669 patients admitted with AHF in our prospective registry. Patients were stratified into tertiles based on UNa in a spot urine sample on admission.Patients with lower UNa were more likely to have a history of prior heart failure admission, β-blockers and diuretics use, and had lower blood pressure and serum sodium level, and higher blood urea nitrogen, estimated glomerular filtration rate, blood glucose and troponin T levels on admission than those with higher UNa. Plasma renin activity, aldosterone, cortisol and dopamine levels were also significantly higher in patients with lower UNa (all p0.001). Furthermore, patients with lower UNa had significantly less weight loss, lower net fluid loss/furosemide equivalent dose and higher incidence of worsening renal function during hospitalization than those with higher UNa (all p0.01). During a median follow-up period of 560days, lower UNa was significantly associated with the composite of all-cause death and worsening heart failure (p0.001). In multivariable Cox-proportional hazards model, UNa remained an independent determinant of long-term adverse events (HR, 1.24, 95% CI, 1.06-1.45, p=0.006).Lower UNa was associated with worse long-term clinical outcomes along with increased neurohormonal activities, impaired response to diuretics and higher incidence of worsening renal function in patients with AHF.

This study was undertaken to assess the impact of acute hyperglycemia (acute-HG) and chronic hyperglycemia (chronic-HG) on short-term outcomes in patients with acute myocardial infarction (AMI). This study consisted of 696 patients with AMI. Acute-HG was defined as admission plasma glucose ≥200 mg/dl and chronic-HG as hemoglobin A1c ≥6.5%. Acute-HG was associated with higher peak serum creatine kinase (4,094 ± 4,594 vs 2,526 ± 2,227 IU/L, p0.001) and in-hospital mortality (9.8% vs 1.6%, p0.001). On the contrary, there was no significant difference in peak creatine kinase (2,803 ± 2,661 vs 2,940 ± 3,181 IU/L, p = 0.59) and mortality (3.3 vs 3.7%, p = 0.79) between patients with chronic-HG and those without. Multivariate analysis showed that admission plasma glucose was an independent predictor of in-hospital mortality (odds ratio 1.15, 95% confidence interval 1.05 to 1.27, p0.001), but hemoglobin A1c was not. When only patients with acute-HG were analyzed, chronic-HG was associated with a significantly smaller infarct size (3,221 ± 3,001 vs 5,904 ± 6,473 IU/L, p0.001) and lower in-hospital mortality (5.5 vs 18.9%, p = 0.01). In conclusion, these results suggested that acute-HG, but not chronic-HG, was associated with adverse short-term outcomes after AMI. Paradoxically, in patients with acute-HG, chronic-HG might abate the adverse effects of acute-HG.

An 85-year-old man with chronic kidney disease (estimated glomerular filtration rate 28.9 ml/min/1.73 m2) underwent percutaneous coronary intervention with optical coherence tomographic (OCT) guidance (ILUMIEN OPTIS, Abbott Laboratories, Abbott Park, Illinois) using low–molecular-weight dextran

Although percutaneous coronary intervention (PCI) routinely achieves good angiographic success, 5% to 30% of patients experience periprocedural myocardial injury (pMI), which is associated with long-term adverse outcomes and immediate adverse events [(1)][1]. Because coronary high-intensity

Acute kidney injury (AKI) and acute hyperglycemia are associated with unfavorable outcomes. The impact of acute hyperglycemia on the development of AKI after acute myocardial infarction (AMI), however, remains unclear. This study was undertaken to assess the relationship between admission glucose and incidence of AKI after AMI.This study consisted of 760 patients with AMI admitted to the National Cerebral and Cardiovascular Center within 48h after symptom onset. Blood sample was obtained on admission and repeated sampling was done at least every 1 or 2 days during the first week. AKI was diagnosed as increase in serum creatinine ≥0.3mg/dl or ≥50% within any 48h. Ninety-six patients (13%) had AKI during hospitalization for AMI, and these patients had higher in-hospital mortality than those without AKI (25% vs. 3%, P0.001). Patients with AKI had higher plasma glucose (PG) on admission than those without (222±105mg/dl vs. 166±69mg/dl, P0.001). The incidence of AKI increased as admission PG rose: 7% with PG120mg/dl; 9% with PG 120-160mg/dl; 11% with PG 160-200mg/dl; and 28% with PG200mg/dl (P0.01). On multivariate analysis admission PG was an independent predictor of AKI (odds ratio, 1.10; 95% confidence interval: 1.03-1.18, P=0.02).Admission hyperglycemia might have contributed to the development of AKI in patients with AMI.

Identification of specific signaling pathways for cardiac hypertrophy in living animals is challenging because no methods have been established to directly observe sequential molecular signaling events at the transcriptional level during pathogenesis. Here, our aim was to develop a useful method for monitoring the specific signaling pathways involved in the development of cardiac hypertrophy in vivo. Expression profiling of the left ventricle by microarray was performed in 2 different mouse models of cardiac hypertrophy: mechanical pressure overload by transverse aortic constriction (TAC) and neurohumoral activation by angiotensin II (Ang II) infusion. To annotate the information on transcription factor-binding sites, we collected promoter sequences and identified significantly frequent transcription factor-binding sites in the promoter regions of coregulated genes from both models (P < 0.05, binomial probability). Finally, we injected a firefly luciferase vector plasmid containing each transcription factor-binding site into the left ventricle in both models. In the TAC and Ang II models, we selected 379 and 12 upregulated genes, respectively. Twenty binding sites for transcription factors, including activator protein 4, were identified in the TAC model, and 4 sites for transcription factors, including ecotropic viral integration 1, were identified in the Ang II model. GATA-binding sites were noted in both models of cardiac hypertrophy. Using the firefly luciferase reporter, we demonstrated the enhancement of transcriptional activity during the progression of cardiac hypertrophy using in vivo imaging in live mice. These results suggested that our approach was useful for the identification of unique transcription factors that characterize different models of cardiac hypertrophy in vivo.

Background The histological diagnosis of cardiac sarcoidosis ( CS ) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells ( DC ) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. Methods and Results The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD 209 + DC and CD 68 + macrophages were more frequently observed ( P CD 163 + M2 macrophages were less frequently observed ( P CD 163 + M2/ CD 68 + macrophage ratio and increased number of CD 209 + DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7–100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas. Conclusions Increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS .

Background Circulating polyunsaturated fatty acid (PUFA) levels are associated with clinical outcomes in cardiovascular diseases including coronary artery disease and chronic heart failure (HF). However, their clinical implications in acute decompensated HF (ADHF) remain unclear. The aim of this study was to investigate the clinical roles of circulating PUFAs in patients with ADHF. Methods Circulating levels of PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) and dihomo-gamma linoleic acid (DGLA), were measured on admission in 685 consecutive ADHF patients. Adverse events were defined as all-cause death and worsening HF. Results During a median follow-up period of 560 days, 262 (38.2%) patients had adverse events. Although patients with adverse events had lower n-6 PUFA (AA + DGLA) level than those without, n-3 PUFA (EPA + DHA) level was comparable between the groups. Kaplan-Meier analyses showed that lower n-6 PUFA level on admission was significantly associated with the composite of all-cause death and worsening HF, all-cause death, cardiovascular death and worsening HF (p < 0.001, p = 0.005, p = 0.021, p = 0.019, respectively). In a multivariate Cox model, lower n-6 PUFA level was independently associated with increased risk of adverse events (HR 0.996, 95% CI: 0.993–0.999, p = 0.027). Conclusions Lower n-6 but not n-3 PUFA level on admission was significantly related to worse clinical outcomes in ADHF patients. Measurement of circulating n-6 PUFA levels on admission might provide information for identifying high risk ADHF patients.

The echo Doppler end-diastolic pulmonary regurgitation (EDPR) gradient correlates well with catheter-derived pulmonary artery diastolic pressure. An elevated EDPR gradient is associated with worse clinical outcomes in patients with stable coronary artery disease. However, the prognostic significance of EDPR gradient in patients with heart failure (HF) is unclear. The aim of the present study was to investigate the prognostic impact of EDPR gradient in HF. We retrospectively examined 751 consecutive hospitalized patients with acute HF. Those with acute coronary syndrome or in-hospital death and those without accessible EDPR gradient data at discharge were excluded. Finally, 265 patients were examined and divided into 2 groups according to EDPR gradient (cutoff 9 mm Hg). Adverse events were defined as worsening HF and death. Patients with elevated EDPR gradient had higher B-type natriuretic peptide, lower age, and lower left ventricular ejection fraction at discharge than those with nonelevated EDPR gradient. During a median follow-up of 429 days, elevated EDPR gradient was independently associated with adverse events (hazard ratio 2.34, 95% CI 1.44 to 3.78, p0.001) after adjustment for confounders. In conclusion, echo Doppler EDPR gradient might be a noninvasive predictor of clinical outcomes in hospitalized patients with HF.

Background— The efficacy and prognosis of percutaneous coronary intervention (PCI) as secondary revascularization in patients with previous coronary artery bypass graft surgery remain uncertain. Methods and Results— We retrospectively evaluated 434 consecutive patients with previous coronary artery bypass graft surgery hospitalized for PCI between 2004 and 2011 (men 84%, age 71 (interquartile range, 66–76) years) and calculated the coronary artery bypass graft Synergy Between Percutaneous Coronary Intervention With Taxus score (CSS) before (baseline CSS) and after PCI (post-PCI CSS). Patients were divided into 2 groups based on median post-PCI CSS: low-score (≤23; n=217) and high-score groups (>23; n=217). Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, myocardial infarction, and unplanned repeat revascularization for myocardial ischemia. The median baseline and post-PCI CSS were 30 (interquartile range, 21–40) and 23 (interquartile range, 14.5–33.5), respectively. During a median follow-up of 69 months, the prevalence of MACE and cardiac death differed significantly between the 2 post-PCI CSS groups (MACE: low, 13.8%; high, 28.6%; P P =0.002). In multivariable analysis, the high post-PCI CSS divided by the median was associated with substantially greater cumulative MACE (hazard ratio, 2.09; 95% confidence interval, 1.31–3.34; P =0.002) and cardiac death (hazard ratio, 2.02; 95% confidence interval, 1.03–3.98; P =0.042) compared with the low post-PCI CSS. Net reclassification improvement analysis revealed that post-PCI CSS resulted in significantly improved prediction of MACE and cardiac death compared with baseline CSS. Conclusions— In this external validation study, the CSS was a potential prognostic factor after subsequent PCI, even for previous coronary artery bypass graft surgery patients.

BACKGROUND Prehospital ECG improves survival following ST-segment elevation myocardial infarction (STEMI). Although a new International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations placed new emphasis on the role of prehospital ECG, this technology is not widely used in Japan. We developed a mobile telemedicine system (MTS) that continuously transmits real-time 12-lead ECG from ambulances in a prehospital setting. This study was designed to compare reperfusion delay between STEMI patients with different prehospital transfer pathways. METHODS AND RESULTS Between 2008 and 2012, 393 consecutive STEMI patients were transferred by ambulance to hospital (PCI-capable center); 301 patients who underwent primary percutaneous coronary intervention (PCI) were enrolled prospectively. We compared time to reperfusion between patients transferred to PCI-capable hospital using the MTS (MTS group, n=37), patients directly transferred from the field to PCI-capable hospital without the MTS (field transfer group, n=125) and patients referred from a PCI-incapable hospital (interhospital transfer group, n=139). Times to reperfusion in the MTS group were significantly shorter than in the other groups, yielding substantial benefits in patients who arrived at a PCI-capable hospital within 6 h after symptom onset. On multivariate analysis, MTS use was an independent predictor of

Aims The prognostic impact of chronic total coronary occlusion (CTO) on implantable cardioverterdefibrillator (ICD) recipients remains unclear. Methods and Results Eighty-four consecutive patients with ischemic heart disease who received ICD therapy for primary or secondary prevention were analyzed. We investigated all-cause mortality and major adverse cardiac events (MACEs) including cardiac death, appropriate device therapy, hospitalization for heart failure, and ventricular assist device implantation. Of the study patients (mean age 70 ± 8 years; 86% men), 34 (40%) had CTO. There were no significant differences in age, left ventricular ejection fraction (LVEF), NYHA functional class III or IV status, and proportion who underwent secondary prevention between patients with CTO (CTO group) and without CTO (non-CTO group). During a median follow-up of 3.8 years (interquartile range 2.7 to 5.4 years), the CTO group tended to have a higher MACE rate (log-rank P=0.054) than the non-CTO group. Within the CTO group, there was no difference in the MACE rate between patients with and without viable myocardium. In patients with ICD for secondary prevention (n=47), 16 patients (34%) with CTO had a higher MACE rate than patients without CTO (logrank P

Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p

Background There are limited studies regarding the prognostic value of coagulation abnormalities in heart failure patients. The clinical significance of prothrombin time international normalized ratio (INR), a widely accepted marker assessing coagulation abnormalities, in acute decompensated heart failure (ADHF) remains unclear. Methods and results Among 561 consecutive patients admitted for ADHF, INR was assessed in 294 patients without prior anticoagulation therapy, acute coronary syndrome, liver disease, or overt disseminated intravascular coagulation. Increased INR on admission was positively associated with increased levels of thrombin-antithrombin complex, C-reactive protein, total bilirubin, γ-glutamyl transpeptidase, inferior vena cava diameter, tricuspid regurgitation severity, markers of neurohormonal activation, and also negatively associated with decreased albumin, cholinesterase, and total cholesterol. In contrast, there was no significant association with left ventricular ejection fraction, serum sodium or blood urea nitrogen. Multivariate analysis showed that increased INR was independently associated with increased all-cause mortality (hazard ratio 1.89 per 0.1 increase, 95% confidence interval 1.14-3.13, P=0.013) during the median follow up of 284 days. Increased INR also had a higher prognostic value compared to risk score models including the Model for End-Stage Liver Disease (MELD) score or the MELD excluding INR (MELD-XI) score. Conclusions Increased INR is an independent predictor of all-cause mortality in ADHF patients without anticoagulation, reflecting coagulation abnormalities and hepatic insufficiency, possibly through systemic inflammation, neurohormonal activation and venous congestion.

Erythropoietin (EPO) is a principal regulator that promotes proliferation and terminal differentiation of erythroid progenitor cells. EPO receptors are expressed not only in hematopoietic lineage cells but also in the cardiovascular system. We performed animal experiments using transgene-rescued EPO receptor null mutant mice (EpoR-/- rescued) that express the EPO receptor exclusively in the hematopoietic cells. The results of these experiments suggest that endogenous EPO/EPO receptor system in the heart exerts cardioprotective effects against myocardial injury induced by ischemia followed by reperfusion and pressure-overload induced left ventricular dysfunction. Many animal experiments have shown that the administration of recombinant human EPO also elicits cardioprotective effects against myocardial injury induced by ischemia and reperfusion. In contrast to the promising results of these animal experiments, recent clinical trials failed to demonstrate the reduction in infarct size or improvement of cardiac function by the administration of recombinant human EPO in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. It should be tested in future clinical studies whether a relatively low dose of recombinant human EPO or its derivatives that have no erythropoietic action reduces infarct size and ameliorates cardiac dysfunction in patients with acute myocardial infarction. In this article, we review implications of anemia associated with chronic heart failure, roles of the endogenous EPO/EPO receptor system, and the effects of the administration of erythropoiesis-stimulating agents in pathologic conditions of the heart by focusing on the EPO receptor as a potential candidate of novel therapeutic targets in cardiovascular diseases.

Chronic left ventricular (LV) pressure overload induced by hypertension is one of the most common causes of heart failure. Earlier reports have shown the cardioprotective effects of erythropoietin (EPO). In the present study, we tested the hypothesis that recombinant human EPO exerts a protective effect against pressure-overload induced LV remodeling. Mice subjected to transverse aortic constriction (TAC) (n = 70) were randomly assigned to the treatment with phosphate buffer solution (PBS) (TAC-PBS) or EPO (2,000 U/kg twice a week) (TAC-EPO). At 8 weeks after TAC, LV weight was comparably increased in both TAC groups compared with sham-operated mice (Sham) (both P < 0.001). The treatment with EPO improved the survival of TAC mice as compared with treatment with PBS (80 vs. 47%, P < 0.01), which was associated with reductions in the extent of myocardial fibrosis and the number of TUNEL positive cardiomyocytes (both P < 0.05). Echocardiography revealed that TAC increased LV chamber diameter and decreased LV fractional shortening compared with Sham (P < 0.05), which was ameliorated by the treatment with EPO (P < 0.05). In TAC-EPO as compared to TAC-PBS, phosphorylation of STAT3, Akt and eNOS was all increased, while phosphorylation of p38 was decreased (all P < 0.05). Importantly, the expression level of VEGF and the capillary density in LV myocardium were similar among the 3 groups. These results suggest that recombinant human EPO ameliorates the cardiac remodeling and the premature death associated with chronic LV pressure overload through the mechanisms independent of angiogenesis.

FSTL1 is an extracellular glycoprotein whose functional significance in physiological and pathological processes is incompletely understood. Recently, we have shown that FSTL1 acts as a muscle-derived secreted factor that is up-regulated by Akt activation and ischemic stress and that FSTL1 exerts favorable actions on the heart and vasculature. Here, we sought to identify the receptor that mediates the cellular actions of FSTL1. We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. DIP2A was present on the cell surface of endothelial cells, and knockdown of DIP2A by small interfering RNA reduced the binding of FSTL1 to cells. In cultured endothelial cells, knockdown of DIP2A by small interfering RNA diminished FSTL1-stimulated survival, migration, and differentiation into network structures and inhibited FSTL1-induced Akt phosphorylation. In cultured cardiac myocytes, ablation of DIP2A reduced the protective actions of FSTL1 on hypoxia/reoxygenation-induced apoptosis and suppressed FSTL1-induced Akt phosphorylation. These data indicate that DIP2A functions as a novel receptor that mediates the cardiovascular protective effects of FSTL1.

We thank Dr Nadir for his interest in our work.1 Among 52 patients with coronary artery embolism (CE), 38 had atrial fibrillation (AF) and the remaining 14 had no evidence of AF on admission and during hospitalization. During follow-up, 2 of 14 patients (14.2%) developed AF; they had idiopathic dilated cardiomyopathy and postprosthetic aortic valve replacement, respectively. The time from discharge to the diagnosis of AF was 17 months and 18 months, respectively. One reason for this low rate of AF detection during follow-up may be ECG monitoring for at least 10 days (median, 18 days) during hospitalization at our institution. As Dr Nadir noted, a previous study reported a median of 41 days of ECG monitoring to detect AF in cryptogenic stroke patients with insertable cardiac monitors.2 …

Follistatin‐like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type‐specific regulation of Fstl1 and its function in a murine model of MI. Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4‐expressing fibroblast lineage cells (Fstl1‐cfKO mice) led to a reduction in injury‐induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1‐cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1.

Background: Where prothrombin time is widely used to monitor anticoagulation in cardiology patients, it is also a classical marker of liver damage. However, the clinical significance of prothrombin time in heart failure patients without anticoagulants is unknown. Therefore, we investigated the prevalence, relationship with clinical characteristics, and prognostic value of prothrombin time in acute decompensated heart failure (ADHF). Method: We prospectively studied 651 consecutive patients admitted for ADHF. Prothrombin time internationalized normalized ratio (PT-INR) was measured on admission in all patients. By excluding patients with oral anticoagulants, acute coronary syndrome and liver diseases, 308 patients were assessed. We assessed the relationship between PT-INR and blood tests, echocardiogram, and hemodynamic parameters from right heart catheterization. Cox regression hazard analysis was performed to assess prognostic value of PT-INR on all-cause mortality and cardiovascular mortality. Results: Of the 308 patients (75±13 years, 192 male), the mean PT-INR value was 1.10. Patients with prolonged PT-INR(>1.10, n=104) had significantly higher total bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase (all p Conclusion: Prolonged PT-INR in ADHF patients without anticoagulants was associated with clinical markers of hepatic congestion and elevated right sided pressure. It was also an independent predictor of all-cause and cardiovascular mortality.

Proximal stenosis adjacent to the orifice of one or both coronary arteries may occur after the arterial switch operation (ASO) for d-transposition of the great arteries (d-TGA). Coronary artery stenosis (CAS) often progresses within the first 6 months postoperatively and may result in myocardial ischemia and infarction. Although percutaneous transluminal coronary balloon angioplasty (PCBA) for CAS within 15 months after ASO for d-TGA has been reported, there is no report of PCBA for CAS in the late period after ASO. We present the results of PCBA for CAS of the left coronary artery performed more than 10 years after ASO in an 11-year-old boy and a 14-year-old boy without complication. The stenosis degree improved in both patients from 81 to 45 and 80 to 54 %, respectively. Restenosis did not occur, and the stenosis degree improved to about 25 % late after PCBA. Although the initial effect of PCBA may not be dramatic, it can improve late after PCBA. It was considered that the optimal balloon-reference vessel ratio was about 1.0, to obtain the minimal effective lumen diameter. PCBA for CAS even if performed many years after ASO is feasible without complication. PCBA can also provide delayed improvement late after the procedure.

BACKGROUND Basal thinning of the interventricular septum (IVS) is an important diagnostic feature of cardiac sarcoidosis (CS), but its long-term prognostic significance remains unclear. METHODS AND RESULTS We examined 74 consecutive patients who were diagnosed with CS. Basal IVS thickness at a point located 10 mm from the aortic annulus was measured. IVS thickness at the left ventricular minor axis level (IVS) was also measured according to the recommended procedure of the American Society of Echocardiography. Patients were divided into 2 groups based on the presence or absence of basal IVS thinning, which was defined as basal IVS ≤4 mm and/or basal IVS/IVS ratio ≤0.6. Basal IVS thinning was observed in 21 patients and was associated with greater long-term adverse events during follow-up (5.1±2.5 years), although the baseline characteristics were comparable between groups (overall, P

We report the results of percutaneous transluminal coronary rotational atherectomy (PTCRA) for localized stenosis caused by Kawasaki disease (KD). Thirteen male and a female, aged 5 to 29 years (median 13 years), underwent PTCRA and the interval from the PTARA to the latest angiogram ranged from 3 months to 16 years (median 6 years). The target vessels were the left anterior descending artery (3 patients), the left circumflex (2), left main trunk (2) and the right coronary artery (7). The immediate results of PTCRA were successful in all patients, and the mean stenosis degree improved from 86 ± 11% to 36 ± 13%. Five cardiac events occurred within one year (acute myocardial infarction 2, transient complete atrioventricular block 1 and re-PTCRA 2). The survival rate and cardiac event free rate at 15 years after PTCRA were 93% and 71%, respectively. For the graft patency, 4 pts who underwent PTCRA within 10 yeas old, had asymptomatic occlusion within 1 year. The patency rate at 15 years after PTCRA was 69%, in 10 pts who underwent it more than 10 years old. Cardiac events and restenosis occurred within a year after PTCRA. The results in patients less than 10 years old was poor. If a graft is patent in one year after procedure, long-term patency may be expected in patients more than 10 years old.

BACKGROUND Cardiac involvement is the worst prognostic determinant in patients with sarcoidosis, but the long-term prognostic significance of corticosteroid therapy for cardiac sarcoidosis (CS) remains unclear. METHODS AND RESULTS We examined 83 consecutive patients diagnosed with CS. Patients were divided into 2 groups based on the presence or absence of corticosteroid therapy at diagnosis. Patients with corticosteroid therapy had lower age and higher rate of positive findings in the myocardium on gallium scintigraphy (Ga) at diagnosis than those without. LVEF, biomarkers, and use of cardiovascular medication were similar between the 2 groups. During the follow-up (7.6±4.4 years), corticosteroid therapy was associated with fewer long-term adverse events (overall, P=0.005; cardiac death, P=0.92; symptomatic arrhythmias, P=0.89; heart failure admission, P