Tomoaki Kanaya

Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism.

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 CHADS2 score of 0 or 1. When those patients were reevaluated using CHA2DS2-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<0.001). 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.

Evaluation of Serial Changes in Tissue Characteristics During Statin-Induced Plaque Regression Using Virtual Histology-Intravascular Ultrasound Studies

Treatment of all coronary arteries is important to improve the prognosis of acute coronary syndrome after early reperfusion of the culprit lesion. Early statin treatment has been reported to cause regression of plaques away from the site of the culprit lesion in patients with acute coronary syndrome. However, the precise mechanism of coronary plaque regression is not well understood. We studied the effects of statins on the regression of coronary plaques away from the culprit lesions in 120 patients with acute coronary syndrome. We used virtual histology-intravascular ultrasound studies to evaluate nonpercutaneous coronary intervention lesions at admission and short-term (2 to 3 weeks) and medium-term (8 to 10 months) follow-up. According to the medium-term evaluation findings, the subjects were divided into 2 groups: a plaque regression group (n = 94) and a plaque progression group (n = 26). In the regression group, the fibrofatty component had decreased at the short-term (-20.0% vs baseline) and had decreased further at the medium-term (-26.7%) evaluations. The fibrous component had also decreased at the short-term (-5.1%) and medium-term (-8.5%) evaluations. In contrast, the necrotic core component showed a tendency to increase in the short term (+12.5%) but then decreased at the medium-term evaluation (-6.3%). In the progression group, the fibrofatty and fibrous components had increased at the short-term (+37.5%, +11.3%) and medium-term (+50.5%, +13.2%) evaluations; however, the necrotic core had decreased at the short-term (-19.0%) and medium-term (-23.8%) evaluations. In conclusion, regarding the course of coronary plaque regression by statin therapy, the plaques began to reduce the volume of fibrofatty and fibrous components in the early phase, associated with a transiently increased necrotic core component. Furthermore, even in the case of plaque progression, statins caused a reduction in the necrotic core.

Late-phase inflammatory response as a feature of in-stent restenosis after drug-eluting stent implantation.

ObjectivesThe aim of this study was to compare pathological features among in-stent restenosis lesions after drug-eluting stent (DES) placement, those after bare metal stent (BMS) placement, and de-novo atherosclerotic lesions. BackgroundRestenosis after stenting is an over-reaction of the wound-healing response after vascular injury, which is characterized by a sequence of inflammation, granulation, extracellular matrix remodeling, and smooth muscle cell proliferation and migration. Recent advances in DES technology could considerably succeed in inhibiting this sequence of events. Thus, we hypothesized that the mechanism of in-stent restenosis after DES stenting might be different from that after BMS stenting as well as atherosclerosis. MethodsTissues obtained by directional atherectomy (DES: seven specimens, BMS: 17 specimens, and de-novo: 15 specimens) were immunostained for T lymphocytes (CD45), macrophages (CD68), smooth muscle cells (&agr;-smooth muscle actin), endothelial cells (von Willebrand factor), and activated platelets (P-selectin). ResultsThe accumulation of T lymphocytes tended to increase and that of macrophages increased significantly in the DES lesions compared with BMS lesions. No significant differences were observed for the other parameters evaluated. ConclusionPathological features of restenotic tissues after DES implantation showed a stronger inflammatory response compared with those after BMS implantation. Thus, the mechanism of restenosis after DES implantation may be different from that observed after BMS implantation.

Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure

Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear.

Pathological features of in-stent restenosis after sirolimus-eluting stent versus bare metal stent placement

A 70-year-old man developed diffuse restenosis in the right coronary artery, in which a bare metal stent (BMS) and two sirolimus-eluting stents (SES) were deployed sequentially. He underwent directional coronary atherectomy (DCA) for in-stent restenosis (ISR) lesions 13 months after both BMS and SES stenting. Further 4 months later, that is, 17 months after stent implantation, however, ISR recurred just at the SES site alone. Then we performed second DCA for the ISR lesion at SES site. The tissue materials obtained from debulking were compared histologically. In the first DCA specimen, accumulation of inflammatory cells such as T lymphocytes and macrophages was observed densely in ISR lesions at SES site but not in those at BMS site, and endothelial coverage was absent in ISR lesions at SES site but present in those at BMS site. In the second DCA specimen, ISR lesions at SES site showed less inflammatory cells, compared with first DCA specimen. ISR lesions after drug-eluting stenting showed persistent signs of delayed or incomplete wound healing and relapsed inflammation, compared with BMS. Thus, the mechanism of restenosis after drug-eluting stenting may be different from that after BMS placement.

Early development of acute kidney injury is an independent predictor of in-hospital mortality in patients with acute myocardial infarction

BACKGROUND Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI), and is associated with adverse outcomes. However, it remains unclear how timing of AKI affects it. This study assessed impact of timing of AKI on prognosis after AMI. METHODS This study consisted of 760 patients with AMI who were admitted within 48h after symptom onset. AKI was diagnosed as increase in creatinine ≥0.3mg/dl or ≥50% within any 48h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48h after admission) and late-AKI (>48h). Early-AKI was classified into transient early-AKI, defined as creatinine returning to the level below the criteria of AKI, and persistent early-AKI. RESULTS Early-AKI occurred in 64 patients (9%) and late-AKI in 32 patients (4%). Patients with early-AKI had significantly higher mortality (35%) than those with late-AKI (7%, p<0.001) and no-AKI (3%, p<0.001). Multivariate analysis showed early-AKI was an independent predictor of in-hospital mortality (OR: 3.38, 95% CI: 1.30-8.76, p=0.013), but late-AKI was not. Among patients with early-AKI, mortality was significantly higher even if AKI was transient (23%, p<0.001). Patients with persistent early-AKI had the highest mortality (66%, p<0.001). CONCLUSIONS Early-AKI was associated with worse outcome. Even if renal function once returned to baseline level, patients with early-AKI tended to be at high risk of mortality.

Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial InfarctionHighlights

Objective— Coronary artery ectasia (CAE) is an infrequently observed vascular phenotype characterized by abnormal vessel dilatation and disturbed coronary flow, which potentially promote thrombogenicity and inflammatory reactions. However, whether or not CAE influences cardiovascular outcomes remains unknown. Approach and Results— We investigated major adverse cardiac events (MACE; defined as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with acute MI. The occurrence of MACE was compared in patients with and without CAE. CAE was identified in 3.0% of study subjects. During the 49-month observation period, CAE was associated with 3.25-, 2.71-, and 4.92-fold greater likelihoods of experiencing MACE (95% confidence interval [CI], 1.88–5.66; P<0.001), cardiac death (95% CI, 1.37–5.37; P=0.004), and nonfatal MI (95% CI, 2.20–11.0; P<0.001), respectively. These cardiac risks of CAE were consistently observed in a multivariate Cox proportional hazards model (MACE: hazard ratio, 4.94; 95% CI, 2.36–10.4; P<0.001) and in a propensity score–matched cohort (MACE: hazard ratio, 8.98; 95% CI, 1.14–71.0; P=0.03). Despite having a higher risk of CAE-related cardiac events, patients with CAE receiving anticoagulation therapy who achieved an optimal percent time in target therapeutic range, defined as ≥60%, did not experience the occurrence of MACE (P=0.03 versus patients with percent time in target therapeutic range <60% or without anticoagulation therapy). Conclusions— The presence of CAE predicted future cardiac events in patients with acute MI. Our findings suggest that acute MI patients with CAE are a high-risk subset who might benefit from a pharmacological approach to controlling the coagulation cascade.

Validation of the Coronary Artery Bypass Graft SYNTAX Score (Synergy Between Percutaneous Coronary Intervention With Taxus) as a Prognostic Marker for Patients With Previous Coronary Artery Bypass Graft Surgery After Percutaneous Coronary Intervention

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<0.001; cardiac death: low, 6.2%; high, 16.7%; 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.

Yummy Food Is Made From Fat and Sugar

events.4,5 Obesity is accompanied by other risk factors, such as diabetes, hypertension, and dyslipidemia, in which adipocytokines secreted from adipose tissues increase insulin sensitivity,6 resulting in increased plaque burden and plaque vulnerability. This “large clinical trial” demonstrates that a Western diet in childhood is associated with increased risk of cardiovascular diseases in the Japanese population. A high-fat diet is associated with endoplasmic reticulum stress in the hypothalamus, which activates the reward system in the brain.7 The reward system consists of a group of neural structures, responsible for motivational salience, in which dopaminergic neurons project from the mesencephalic ventral tegmental area (VTA) to the cerebral cortex. In animal and human brains, the satisfaction of wants or desires stimulates the reward system, which recognizes these stimuli as a positive emotion or delectation. It is an essential system for the survival of individuals and their offspring because it is associated with instinctive behaviors, such as eating, sexual intercourse, and breastfeeding. Eating acts as a reward stimulus and activates dopaminergic neurons in the VTA.8 Recently, the similarity between food addiction and drug dependency has garnered a lot of attention.9 Drug dependency raises the reward system threshold with each dose. Obesity, similar to cocaine dependency, decreases the activity of dopaminergic receptors in the dorsal striatum of the basal ganglia, leading to a decrease in reward stimuli. Mice fed a high-fat diet develop O ver the past several decades, postmortem studies have provided novel insights on coronary atherosclerosis, and investigators have established the relationship between cardiovascular risk factors and the extension of atherosclerosis. They have concluded that the fundamental cause of coronary events is plaque vulnerability and the subsequent rupture or erosion of plaques. Following acknowledgment of their pleiotropic effects, statins have been widely used for healing vulnerable coronary plaques as well as lowering lipid levels. Nevertheless, residual risks remain, even after treatment with strong statins, and thus we should focus on the next target for further risk reduction. Recent innovations in intravascular imaging modalities have greatly contributed to the precise pathophysiological diagnosis of coronary artery disease, as well as to decision making on coronary intervention procedures. For assessing coronary plaque morphology, optical coherence tomography (OCT) provides superior spatial resolution.1 With a resolution 10-fold higher than that of intravascular ultrasound imaging, OCT technology provides precise information about thrombi, spotty calcifications, and fibrous caps,2 and therefore, its images provide an “in vivo histology.” In this issue of the Journal, De Rosa et al3 assess the relationship between coronary plaque characteristics and cardiovascular risk factors using their own OCT observations. In their results, diabetes, prediabetes, and obesity were the only independent predictors of thin-cap fibroatheroma, and diabetes and prediabetes were the only independent predictors of plaque erosion. Although patients enrolled in their study were not aggressively treated with statins, their lipid profiles had favorable values. This may be the reason why comorbidity with dyslipidemia did not contribute to OCT-observed plaque vulnerability in the multivariate analysis of their study. Therefore, this study indicates that we need to focus on glucose metabolism and obesity, independently of lipid profiles. The novelty of this study was its use of OCT images for the in vivo histological analysis of plaque morphology. After the 1940’s Pacific war, the Japanese lifestyle underwent a “sea change” under the American occupation. School lunches were introduced to prevent childhood hunger, and the food preferences of the Japanese population were changed. Since the opening of the first McDonald’s fast food restaurant in Tokyo in the 1970 s, the prevalence of fast food has facilitated a high-fat and/or high-sugar diet among Japanese children. This has led to increased morbidity from diabetes, obesity, and related cardiovascular Article p 1165

Characterization of coronary atherosclerosis by intravascular imaging modalities

Coronary artery disease (CAD) is highly prevalent in Western countries and is associated with morbidity, mortality, and a significant economic burden. Despite the development of anti-atherosclerotic medical therapies, many patients still continue to suffer from coronary events. This residual risk indicates the need for better risk stratification and additional therapies to achieve more reductions in cardiovascular risk. Recent advances in imaging modalities have contributed to visualizing atherosclerotic plaques and defining lesion characteristics in vivo. This innovation has been applied to refining revascularization procedure, assessment of anti-atherosclerotic drug efficacy and the detection of high-risk plaques. As such, intravascular imaging plays an important role in further improvement of cardiovascular outcomes in patients with CAD. The current article reviews available intravascular imaging modalities with regard to its method, advantage and disadvantage.