Hiroshi Funayama

Peak C-Reactive Protein Level Predicts Long-Term Outcomes in Type B Acute Aortic Dissection

Acute aortic dissection (AAD) is associated with an inflammatory reaction, as evidenced by elevated inflammatory markers, including C-reactive protein (CRP). The association between the peak CRP level and long-term outcomes in type B AAD has not been systematically investigated. The purpose of this study was to investigate whether the peak CRP level during admission predicts long-term outcomes in type B AAD. We conducted a clinical follow-up study of type B AAD. We divided the study population into 4 groups according to the tertiles of peak CRP levels (T1: 0.60 to 9.37 mg/dL; T2: 9.61 to 14.87 mg/dL; T3: 14.90 to 32.60 mg/dL; and unavailable peak CRP group). Multivariate Cox regression analysis was applied to investigate whether the tertiles of peak CRP predict adverse events even after adjusting for other variables. A total of 232 type B AAD patients were included in this analysis. The median follow-up period was 50 months. CRP reached its peak on day 4.5±1.7. Mean peak CRP values in T1, T2, and T3 were 6.4±2.4, 12.0±1.5, and 19.5±4.0 mg/dL, respectively. There were 65 events (39 deaths and 26 aortic events) during the follow-up. T3 and T2 (versus T1) were strong predictors of adverse events (T3: hazard ratio: 6.02 [95% CI: 2.44 to 14.87], P=0.0001; T2: hazard ratio: 3.25 [95% CI: 1.37 to 7.71], P=0.01) after controlling for all of the confounding factors. In conclusion, peak CRP is a strong predictor for adverse long-term events in patients with type B AAD.

Impact of acute hyperglycemia during primary stent implantation in patients with ST-elevation myocardial infarction

BACKGROUND Acute hyperglycemia is associated with increased mortality rates in patients with acute coronary syndrome. OBJECTIVE This study aimed to evaluate the relationship between the glucose level and clinical variables during primary intervention in patients with ST-elevation acute myocardial infarction (STEMI). METHODS AND RESULTS Of consecutive 94 patients with STEMI treated by primary stent implantation, acute hyperglycemia (plasma glucose level on admission>198 mg/dl) was recognized in 29 patients. There were no significant differences in baseline characteristics, except for the presence of diabetes and HbA(1c) level, between patients with and without acute hyperglycemia. In patients with acute hyperglycemia, corrected TIMI frame counts were significantly higher compared with those in patients without acute hyperglycemia (46.3+/-30.3 vs. 34.0+/-17.9, p=0.02). And corrected TIMI frame count was independently associated with plasma glucose level (p=0.006). Maximum level of creatine kinase (CK) and CK-MB were significantly higher in patients with acute hyperglycemia (CK, 4840.0+/-4690.3 vs. 2410.7+/-2302.9 IU, p=0.001; CK-MB, 315.3+/-257.7 vs. 195.9+/-191.1, p=0.01). CONCLUSION The presence of acute hyperglycemia was associated with the impairment of epicardial coronary flow after primary stent implantation. This mechanism might be responsible for the increased infarct size.

Elevation of plasma placental growth factor in the patients with ischemic cardiomyopathy

BACKGROUND Placental growth factor (PlGF), which is a member of the vascular endothelial growth factor family, stimulates angiogenesis and collateral growth in ischemic tissues. In addition, PlGF has been known to be a useful biomarker of vascular inflammation. This study was undertaken to examine whether plasma PlGF levels were increased in patients with congestive heart failure (CHF). METHODS Ninety-eight patients with systolic heart failure (ejection fraction <40%) and twenty control subjects were enrolled. The patients were divided into four subgroups according to the criteria of NYHA functional class. Plasma PlGF, tumor necrosis factor (TNF)-alpha, brain natriuretic peptide (BNP), norepinephrine, high-sensitive C-reactive protein (hs-CRP) were determined. RESULTS In analysis of all the subjects, there was no significant difference in plasma PlGF levels among the subgroups of NYHA classes and the controls. In the ischemic cardiomyopathy (ICM) patients, however, plasma PlGF levels were significantly increased according to the severity of NYHA class; control: 8.9+/-0.5; NYHA I: 9.4+/-1.1, NYHA II: 9.7+/-1.9, NYHA III: 14.6+/-1.2, NYHA IV: 17.9+/-1.9 pg/ml (p=0.0006). Plasma PlGF levels correlated positively with BNP (r=0.53, p=0.0003) and hs-CRP (r=0.23, p=0.02) in the ICM patients, whereas there was not any correlation between plasma PlGF levels and other variable values in the non-ICM patients. CONCLUSIONS In the ICM patients, plasma PlGF levels are increased according to the severity of heart failure. These results may indicate that augmented release of PlGF is involved in the pathogenesis of cardiomyopathy derived from chronic myocardial ischemia.

Interaction between human monocytes and vascular smooth muscle cells induces vascular endothelial growth factor expression

The objective of this study was to investigate whether synthesis of vascular endothelial growth factor (VEGF), a major mitogen for vascular endothelial cells, was induced by a cell-to-cell interaction between monocytes and vascular smooth muscle cells (VSMCs). Human VSMCs and THP-1 cells (human monocytoid cell) were cocultured. VEGF levels in the coculture medium were determined by enzyme-linked immunosorbent assay. Northern blot analysis of VEGF mRNA was performed using a specific cDNA probe. Immunohistochemistry was performed to determine which types of cell produce VEGF. Adding THP-1 cells to VSMCs for 24 h increased VEGF levels of the culture media, 8- and 10-fold relative to those of THP-1 cells and VSMCs alone, respectively. Northern blot analysis showed that VEGF mRNA expression was induced in the cocultured cells and peaked after 12 h. Immunohistochemistry disclosed that both types of cell in the coculture produced VEGF. Separate coculture experiments revealed that both direct contact and a soluble factor(s) contributed to VEGF production. Neutralizing anti-interleukin (IL)-6 antibody inhibited VEGF production by the coculture of THP-1 cells and VSMCs. A cell-to-cell interaction between monocytes and VSMCs induced VEGF synthesis in both types of cell. An IL-6 mediated mechanism is at least partially involved in VEGF production by the cocultures. Local VEGF production induced by a monocyte-VSMC interaction may play an important role in atherosclerosis and vascular remodeling.

Plaque Characteristics of the Coronary Segment Proximal to the Culprit Lesion in Stable and Unstable Patients

Identifying vulnerable plaque is important for preventing an acute coronary event. The present study examined the relationship between the clinical presentation of coronary artery disease and the plaque characteristics of nonculprit segment assessed by virtual histology intravascular ultrasound (VH‐IVUS).

Comparison of Frequency of Complications With On-Label Versus Off-Label Use of Rotational Atherectomy

Although rotational atherectomy (RA) is used for complex lesions in percutaneous coronary intervention, there are several contraindications and precautions. The purpose of our study was to compare complications between off-label and on-label use of RA. We identified 250 consecutive patients who underwent RA. Off-label characteristics included saphenous vein graft lesions, presence of thrombus, unprotected left main stenosis, coronary artery dissection, acute myocardial infarction (MI), left ventricular dysfunction, 3-vessel disease, long lesion (≥ 25 mm), or angulated lesion (≥ 45°). Patients who had ≥ 1 off-label characteristic were assigned to the off-label group (156 patients), and patients who had no off-label characteristics were assigned to the on-label group (94 patients). Occurrence of slow flow or periprocedural MI in the off-label group was higher than that in the on-label group (slow flow 30% vs 18%, p = 0.06; MI 8.8% vs 2.1%, p = 0.04), whereas severe complications such as burr entrapment, transection of the guidewire, or perforation were rare in the 2 groups. In conclusion, compared to the on-label group, the off-label group had a higher incidence of slow flow and periprocedural MI. Severe complications such as burr entrapment, transection of the guidewire, or perforation were rare in the 2 groups.

Determinants of long-term mortality in patients with type B acute aortic dissection.

BACKGROUND Type B acute aortic dissection (AAD) carries a high short- and midterm mortality rate; however, knowledge related to long-term outcome is largely incomplete. The objective of this study was to identify long-term predictors including antihypertensive medications in type B AAD. METHODS We conducted a clinical follow-up study on 202 type B AAD patients. Univariate and multivariate Cox regression analyses were performed to identify predictors of mortality. RESULTS There were 44 postdischarge deaths in 202 consecutive type B AAD patients with a median follow-up of 55 months. In univariate Cox regression analysis, age (10 year incremental: hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.35-2.46, P < 0.0001), previous myocardial infarction or angina pectoris (HR 3.93, 95% CI 1.72-8.99, P = 0.001), and impaired renal function (HR 4.90, 95% CI 2.48-9.65, P < 0.0001) were predictors of death. Calcium channel blockers (CCBs), beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors as antihypertensive medications at discharge were predictors of increased survival. In multivariate Cox regression analysis, CCBs were a significant predictor of increased survival (vs. no antihypertensive medication at discharge: HR 0.38, 95% CI 0.15-0.97, P = 0.04). Impaired renal function was a significant predictor of death (HR 3.41, 95% CI 1.58-7.33, P = 0.002). No antihypertensive medication at discharge group was significantly associated with increased mortality (vs. 1 class of antihypertensive medication: HR 9.51, 95% CI 1.85-48.79, P = 0.007). CONCLUSIONS Impaired renal function was a predictor for adverse outcome in patients with type B AAD. The use of CCBs as antihypertensive medication at discharge was associated with increased survival.

Incidence and Determinants of Complications in Rotational Atherectomy: Insights From the National Clinical Data (J-PCI Registry)

Background—The usage of rotational atherectomy (RA) is growing in the current percutaneous coronary intervention (PCI) because of the expansion of PCI indication to more complex lesions. However, the complications after RA have been linked to procedure-related morbidity and mortality. The purpose of this study was to investigate the incidence and determinants of complications in RA using a large nationwide registration system in Japan (J-PCI). Methods and Results—The primary composite outcome of this study was defined as the occurrence of in-hospital death, cardiac tamponade, and emergent surgery after RA. A total of 13 335 RA cases (3.2% of registered PCI cases) were analyzed. The composite outcome was observed in 175 cases (1.31%) and included 80 in-hospital deaths (0.60%), 86 tamponades (0.64%), and 24 emergent surgeries (0.18%). The clinical variables associated with occurrence of the composite outcome were age (odds ratio [OR] 1.03 per unit increment, 95% confidence interval [CI] 1.02–1.05), impaired kidney function (OR 1.59, 95% CI 1.15–2.19), previous myocardial infarction (OR 1.69, 95% CI 1.21–2.35), emergent PCI (OR 4.02, 95% CI 1.66–8.27), and triple-vessel disease (versus single-vessel disease: OR 2.17, 95% CI 1.43–3.28). Notably, institutional volume of RA cases was inversely associated with the composite outcomes (high- versus low-volume institution: OR 0.56, 95% CI 0.36–0.89). Conclusions—The reported incidence of important procedure-related complication rate was 1.3%, with each component ranging between 0.2% and 0.6% in J-PCI. Its determinants were both patient related (age, impaired kidney function, and previous myocardial infarction) and procedure related (emergent procedures, number of diseased vessels, and institutional volume of RA).

Myeloperoxidase may contribute to the no-reflow phenomenon in patients with acute myocardial infarction

BACKGROUND The no-reflow phenomenon is a deteriorating factor for prognosis of acute myocardial infarction (AMI). Leukocyte enzymes may be involved in developing the no-reflow phenomenon. The aim of this study was to clarify the association of myeloperoxidase, a leukocyte enzyme, with the no-reflow phenomenon in patients with AMI after percutaneous coronary inetervention (PCI). METHODS We enrolled 50 patients with AMI whose infarct-related coronary arteries were rescued by thrombectomy devices. Blood samples were collected from peripheral vein (PV), ostium and culprit lesion of infarct-related coronary artery. Myeloperoxidase, elastase and interleukin (IL)-8 were measured by ELISA. Antegrade blood flow in the infarct-related coronary artery and myocardial perfusion were evaluated according to the corrected TIMI frame counts (cTFC) and the myocardial blush grade (MBG). RESULTS Plasma myeloperoxidase and IL-8 levels at the ostium and the culprit lesion of infarct-related coronary artery were significantly greater than those in PV. No-reflow was found in 10 patients (20%). Plasma levels of myeloperoxidase at the culprit lesion of infarct-related coronary artery were significantly greater in the patients with no-reflow than those without no-reflow. Plasma myeloperoxidase levels at the culprit lesion of infarct-related coronary artery positively correlated with the cTFC. Also, plasma myeloperoxidase levels were significantly higher in the patients with MBG 0-1 than those with MBG 2-3. CONCLUSIONS The present findings indicate that local myeloperoxidase levels in the culprit coronary artery may contribute to the no-reflow phenomenon in the patients with AMI.

Association between deteriorated renal function and long-term clinical outcomes after percutaneous coronary intervention.

Acute renal insufficiency after percutaneous coronary artery intervention (PCI) is a strong predictor of adverse events. However, the effect of chronic renal impairment on the long-term outcomes after PCI has not been well established. The aim of this study was to evaluate the incidence of deteriorated renal function during the chronic phase after PCI and its impact on clinical outcomes. We enrolled 282 consecutive patients who underwent PCI and had serum creatinine measured during the chronic phase (at least 3 months after PCI). We divided the study population into two groups: an advanced group that had an increase in stage of chronic kidney disease during the chronic phase, and a preserved group that included the remainder of the study population. There were 43 patients in the advanced group. We evaluated the incidence of major adverse cardiac events (MACE) that included all-cause death, nonfatal myocardial infarction, and rehospitalization with heart failure or angina pectoris. The rate of rehospitalization for heart failure and angina pectoris was significantly higher in the advanced group than in the preserved group (19.0% vs 6.8%, P < 0.01). In multivariate Cox regression analysis, the advanced group was associated with MACE (hazard ratio 3.50, 95% confidence interval 1.49–8.22, P < 0.01). Deterioration of renal function during long-term follow-up after percutaneous coronary intervention was associated with adverse cardiac events.