Nobuaki Kokubu

Sirolimus-Eluting Stent Versus Balloon Angioplasty for Sirolimus-Eluting Stent Restenosis: Insights From the j-Cypher Registry

Background— Optimal treatment strategies for restenosis of sirolimus-eluting stents (SES) have not been adequately addressed yet. Methods and Results— During the 3-year follow-up of 12 824 patients enrolled in the j-Cypher registry, 1456 lesions in 1298 patients underwent target-lesion revascularization (TLR). Excluding 362 lesions undergoing TLR for stent thrombosis or TLR using treatment modalities other than SES or balloon angioplasty (BA), 1094 lesions with SES-associated restenosis in 990 patients treated with either SES (537 lesions) or BA (557 lesions) constituted the study population for the analysis of recurrent TLR and stent thrombosis after the first TLR. Excluding 24 patients with both SES- and BA-treated lesions, 966 patients constituted the analysis set for the mortality outcome. Cumulative incidence of recurrent TLR in the SES-treated restenosis lesions was significantly lower than that in the BA-treated restenosis lesions (23.8% versus 37.7% at 2 years after the first TLR; P<0.0001). Among 33 baseline variables evaluated, only hemodialysis was identified to be the independent risk factor for recurrent TLR by a multivariable logistic regression analysis. After adjusting for confounders, repeated SES implantation was associated with a strong treatment effect in preventing recurrent TLR over BA (odds ratio, 0.44; 95% confidence interval, 0.32 to 0.61; P<0.0001). The 2-year mortality and stent thrombosis rates between the SES- and the BA-treated groups were 10.4% versus 10.8% (P=0.4) and 0.6% versus 0.6%, respectively. Conclusions— Repeated implantation of SES for SES-associated restenosis is more effective in preventing recurrent TLR than treatment with BA, without evidence of safety concerns.

Local Production of Fatty Acid–Binding Protein 4 in Epicardial/Perivascular Fat and Macrophages Is Linked to Coronary Atherosclerosis

Objective—Fatty acid–binding protein 4 (FABP4) is expressed in adipocytes and macrophages, and elevated circulating FABP4 level is associated with obesity-mediated metabolic phenotype. We systematically investigated roles of FABP4 in the development of coronary artery atherosclerosis. Approach and Results—First, by immunohistochemical analyses, we found that FABP4 was expressed in macrophages within coronary atherosclerotic plaques and epicardial/perivascular fat in autopsy cases and macrophages within thrombi covering ruptured coronary plaques in thrombectomy samples from patients with acute myocardial infarction. Second, we confirmed that FABP4 was secreted from macrophages and adipocytes cultured in vitro. Third, we investigated the effect of exogenous FABP4 on macrophages and human coronary artery–derived smooth muscle cells and endothelial cells in vitro. Treatment of the cells with recombinant FABP4 significantly increased gene expression of inflammatory markers in a dose-dependent manner. Finally, we measured serum FABP4 level in the aortic root (Ao-FABP4) and coronary sinus (CS-FABP4) of 34 patients with suspected or known coronary artery disease. Coronary stenosis score assessed by the modified Gensini score was weakly correlated with CS-FABP4 but was not correlated with Ao-FABP4. A stronger correlation (r=0.59, P<0.01) was observed for the relationship between coronary stenosis score and coronary veno-arterial difference in FABP4 level, (CS-Ao)-FABP4, indicating local production of FABP4 during coronary circulation in the heart. Multivariate analysis indicated that (CS-Ao)-FABP4 was an independent predictor of the severity of coronary stenosis after adjustment of conventional risk factors. Conclusions—FABP4 locally produced by epicardial/perivascular fat and macrophages in vascular plaques contributes to the development of coronary atherosclerosis.

Post-load hyperglycemia as an important predictor of long-term adverse cardiac events after acute myocardial infarction: a scientific study

BackgroundDiabetes mellitus (DM) and impaired glucose tolerance (IGT) are risk factors for acute myocardial infarction (AMI). However, it is unknown whether hyperglycemic state is associated with increased major adverse cardiovascular events (MACE) after AMI. In this study, we evaluated the relationship between glucometabolic status and MACE in patients after AMI, and determined the critical level of 2 h post-load plasma glucose that may be used to predict MACE.MethodsAMI patients (n = 422) were divided into 4 groups as follows: normal glucose tolerance (NGT) group, IGT group, newly diagnosed DM (NDM) group, and previously known DM (PDM) group. MACE of the 4 groups were compared for 2 years from AMI onset.ResultsThe NDM group had a significantly higher event rate than the IGT and NGT groups and had a similar event rate curve to PDM group. The logistic models analyses revealed that 2 h post-load plasma glucose values of ≥160 mg/dL was the only independent predictor of long-term MACE after AMI (p = 0.028, OR: 1.85, 95% CI: 1.07-3.21). The 2-year cardiac event rate of patients with a 2 h post-load hyperglycemia of ≥160 mg/dL was significantly higher than that of patients with 2 h post-load glucose of <160 mg/dL (32.2% vs. 19.8%, p < 0.05) and was similar to that of PDM group (37.4%, p = 0.513).ConclusionsNDM increases the risk of MACE after AMI as does PDM. Particularly, post-AMI patients with a 2 h post-load hyperglycemia ≥160 mg/dL may need adjunctive therapy after AMI.

Diffuse in-stent restenosis of CYPHER® stent due to hypersensitivity reaction confirmed by pathohistological findings

The use of drug-eluting stents (DES) reduces the risk of repeat revascularization without increase of death and myocardial infarction compared to standard bare metal stents. However, in-stent restenosis (ISR) after DES implantation still occurs. Here, we report a rare case with a diffuse ISR after CYPHER® stent implantation because of chronic inflammation and hypersensitivity reactions, confirmed by pathohistological findings.

Inter-vendor variability of left ventricular volumes and strains determined by three-dimensional speckle tracking echocardiography.

Inter‐vendor discordance in three‐dimensional speckle‐tracking echocardiography (3DS) remains uncharacterized. We aimed to examine inter‐vendor discordance of left ventricular (LV) volumes, and functional parameters and their reproducibilities between two commercially available 3DS systems.

Delayed Visceral Bleeding from Liver Injury After Cardiopulmonary Resuscitation

BACKGROUND Visceral injury is a life-threatening complication of cardiopulmonary resuscitation (CPR); however, the clinical significance has been masked by the lethal outcome of out-of-hospital cardiac arrest (OHCA). OBJECTIVE The objective is to share our experience of successful treatment of OHCA patients with serious, CPR-related visceral complications. CASE REPORTS We report two cases of cardiac-origin OHCA with liver injury exacerbated by heparinization during mechanical circulatory support. Although both patients presented with delayed massive liver bleeding (intrahepatic or peritoneal) that compromised hemodynamic status, one patient was successfully treated by selective transcatheter arterial embolization and the other by a surgical procedure. CONCLUSION Preventive measures such as careful CPR, as well as interventional or surgical repair after the early diagnosis of visceral injury, are required to improve the outcome in some cases of OHCA.

Reduction of endoplasmic reticulum stress inhibits neointima formation after vascular injury

Endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) are predominant features of pathological processes. However, little is known about the link between ER stress and endovascular injury. We investigated the involvement of ER stress in neointima hyperplasia after vascular injury. The femoral arteries of 7-8-week-old male mice were subjected to wire-induced vascular injury. After 4 weeks, immunohistological analysis showed that ER stress markers were upregulated in the hyperplastic neointima. Neointima formation was increased by 54.8% in X-box binding protein-1 (XBP1) heterozygous mice, a model of compromised UPR. Knockdown of Xbp1 in human coronary artery smooth muscle cells (CASMC) in vitro promoted cell proliferation and migration. Furthermore, treatment with ER stress reducers, 4-phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), decreased the intima-to-media ratio after wire injury by 50.0% and 72.8%, respectively. Chronic stimulation of CASMC with PDGF-BB activated the UPR, and treatment with 4-PBA and TUDCA significantly suppressed the PDGF-BB-induced ER stress markers in CASMC and the proliferation and migration of CASMC. In conclusion, increased ER stress contributes to neointima formation after vascular injury, while UPR signaling downstream of XBP1 plays a suppressive role. Suppression of ER stress would be a novel strategy against post-angioplasty vascular restenosis.

Coronary vasospasm secondary to allergic reaction following food ingestion: a case of type I variant Kounis syndrome

Coronary vasospasm can be induced by allergic reactions with some chemical mediators, and the angina and myocardial infarction secondary to allergy-induced coronary vasospasm are referred to as “Kounis syndrome.” Only two cases of Kounis syndrome following food ingestion have been reported. However, they had pre-existing atheromatous coronary artery disease, and no provocation test to induce coronary vasospasm was done. We describe here another probable case of allergic vasospasm after food intake. To the best of our knowledge, this is the first documented report of a patient with food-induced allergic vasospasm subsequent to the provocation test with ergometrine maleate.

Off-hours presentation does not affect in-hospital mortality of Japanese patients with acute myocardial infarction: J-MINUET substudy

BACKGROUND The association between patients with acute myocardial infarction (AMI) who present during off-hours and clinical outcomes has not been fully elucidated. METHODS We investigated 3283 consecutive patients with AMI who were selected from a prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation on in-hospital mortality among Japanese patients with AMI. RESULTS Among the patients, 52% presented in off-hours. Baseline characteristics were comparable, although those who presented during off-hours were younger and had a higher incidence of ST-elevation myocardial infarction and advanced Killip Class. The time from symptom onset to presentation time was shorter in off-hour patients (120min, interquartile range 60 to 256 vs. 215min, interquartile range 90 to 610, p<0.0001). In contrast, 85% of patients underwent primary percutaneous coronary intervention (PCI) and door to balloon time was comparable between the groups (74min, interquartile range 52 to 113 vs. 75min, interquartile range 52 to 126, p=0.34). The rates of in-hospital mortality were comparable (6.2% vs 6.8%, p=0.39). Multivariate logistic regression analysis revealed that off-hours presentation was not significantly associated with in-hospital mortality [odds ratio (OR) 0.94; 95% CI, 0.68-1.30, p=0.70]. CONCLUSION The clinical impact of presenting during off-hours or regular hours on AMI patients in Japan is comparable in contemporary practice. TRIAL REGISTRATION UMIN Unique trial Number: UMIN000010037.

Usefulness of a 0.010-inch guidewire compatible balloon for crossing stent-jailed sidebranches

Abstract Failure of the balloon to pass through for a side branch in spite of wire crossing occasionally occurs due to a jailed stent during treatment of bifurcation lesions. In this report, we describe a novel 0.010-inch coronary guidewire compatible balloon (IKAZUCHI 10™ ) that is effective for crossing a side branch through the jailed stent strut, while another standard 0.014-inch guidewire compatible small balloon was unable to cross the same lesion. This novel 0.010-inch guidewire compatible balloon may be useful for a side branch that is difficult to cross through the stent strut.