CXC-chemokine receptor 4 antagonist AMD3100 promotes cardiac functional recovery after ischemia/reperfusion injury via endothelial nitric oxide synthase-dependent mechanism.

BACKGROUND: CXC-chemokine receptor 4 (CXCR4) regulates the retention of stem/progenitor cells in the bone marrow (BM), and the CXCR4 antagonist AMD3100 improves recovery from coronary ligation injury by mobilizing stem/progenitor cells from the BM to the peripheral blood. Thus, we investigated whether AMD3100 also improves recovery from ischemia/reperfusion injury, which more closely mimics myocardial infarction in patients, because blood flow is only temporarily obstructed. METHODS AND RESULTS: Mice were treated with single subcutaneous injections of AMD3100 (5 mg/kg) or saline after ischemia/reperfusion injury. Three days later, histological measurements of the ratio of infarct area to area at risk were smaller in AMD3100-treated mice than in mice administered saline, and echocardiographic measurements of left ventricular function were greater in the AMD3100-treated mice at week 4. CXCR4(+) cells were mobilized for just 1 day in both groups, but the mobilization of sca1(+)/flk1(+) cells endured for 7 days in AMD3100-treated mice compared with just 1 day in the saline-treated mice. AMD3100 upregulated BM levels of endothelial nitric oxide synthase (eNOS) and 2 targets of eNOS signaling, matrix metalloproteinase-9 and soluble Kit ligand. Furthermore, the loss of BM eNOS expression abolished the benefit of AMD3100 on sca1(+)/flk1(+) cell mobilization without altering the mobilization of CXCR4(+) cells, and the cardioprotective effects of AMD3100 were retained in eNOS-knockout mice that had been transplanted with BM from wild-type mice but not in wild-type mice with eNOS-knockout BM. CONCLUSIONS: AMD3100 prolongs BM progenitor mobilization and improves recovery from ischemia/reperfusion injury, and these benefits appear to occur through a previously unidentified link between AMD3100 and BM eNOS expression.

Impact of myocardial reperfusion status on QT dispersion after successful recanalization of the infarct-related artery in acute myocardial infarction.

OBJECTIVE: To determine whether adequate myocardial perfusion status after transluminal recanalization is associated with prompt improvement of QT dispersion (QTd). BACKGROUND: Transluminal recanalization of the infarct-related coronary artery in acute myocardial infarction aims to promptly restore myocardial perfusion, to maximize electrical and mechanical recovery. QTd represents the heterogeneity of ventricular repolarization, which may affect electrical stability. METHODS: Forty patients who underwent primary percutaneous coronary intervention for their first anterior acute ST-elevation myocardial infarction were prospectively enrolled. Myocardial reperfusion status was assessed by myocardial blush grade (MBG) on the final angiogram after successful recanalization (Thrombolysis In Myocardial Infarction Grade 3 flow). RESULTS: Preprocedural QTd was similar in patients with final MBG 0-1, 2, and 3 (76 ± 24, 67 ± 13, and 69 ± 13 milliseconds, respectively; P = 0.661). After recanalization, QTd decreased in patients with MBG 3 (39 ± 16 milliseconds, P < 0.001) but not in patients with MBG 0-1 (74 ± 20 milliseconds) or MBG 2 (82 ± 16 milliseconds). Multivariate analysis showed that postprocedural MBG was an independent predictor of QTd after recanalization (standardized regression coefficient = -0.628, P < 0.001). CONCLUSIONS: Adequate tissue perfusion may be crucial for electrical stability of the myocardium after reperfusion.

CXCR4 blockade augments bone marrow progenitor cell recruitment to the neovasculature and reduces mortality after myocardial infarction.

We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered after the onset of myocardial infarction increased circulating EPC counts and myocardial vascularity, reduced fibrosis, and improved cardiac function and survival. In mice transplanted with traceable BM cells, AMD increased BM-derived cell incorporation in the ischemic border zone. In contrast, continuous infusion of AMD, although increasing EPCs in the circulation, worsened outcome by blocking EPC incorporation. In addition to its effects as a CXCR4 antagonist, AMD also up-regulated VEGF and matrix metalloproteinase 9 (MMP-9) expression, and the benefits of AMD were not observed in the absence of MMP-9 expression in the BM. These findings suggest that AMD3100 preserves cardiac function after myocardial infarction by enhancing BM-EPC-mediated neovascularization, and that these benefits require MMP-9 expression in the BM, but not in the ischemic region. Our results indicate that AMD3100 could be a potentially useful therapy for the treatment of myocardial infarction.

Percutaneous transluminal coronary angioplasty for postoperative left coronary artery stenosis following surgical reconstruction of congenital atresia of the left main coronary artery.

Congenital atresia of the left main coronary ostium is a rare coronary artery anomaly. A 3-year-old boy who was asymptomatic had a heart murmur because of mitral regurgitation. He underwent reconstruction of the left main coronary artery, but stenosis occurred in the early postoperative period. Although the patient underwent repair of the coronary artery stenosis, the distal portion of the left coronary artery re-stenosed. Percutaneous transluminal coronary angioplasty for the stenosis was performed successfully and there has not been any sign of re-stenosis for 30 months to date.

Contrast-Induced Nephropathy and Oxygen Pretreatment in Patients With Impaired Renal Function.

INTRODUCTION: Contrast-induced nephropathy is a complication following coronary angiography and percutaneous coronary intervention. Because contrast-induced nephropathy is a predictor of long-term mortality in patients with ischemic heart disease undergoing percutaneous coronary intervention, preventive strategies are required. We assessed the effects of periprocedural oxygenation on contrast-induced nephropathy among patients with pre-existing renal dysfunction. METHODS: A total of 200 consecutive patients with impaired renal function (estimated glomerular filtration < 60 ml/min per 1.73 m2) undergoing elective cardiovascular angiography were randomly assigned to an oxygenation treatment (n = 100) or control group (n = 100). In oxygenation treatment, pure oxygen (2 L/min) was administered for 10 minutes before exposure to contrast medium. The primary endpoint was the incidence of contrast-induced nephropathy, defined as a ≥ 25% increase in serum creatinine levels from baseline within 48 hours of exposure. RESULTS: In the oxygenation treatment group, partial pressure of arterial oxygen was higher (135 ± 25 mm Hg vs. 84 ± 10 mm Hg, P < 0.001); contrast-induced nephropathy incidence was lower (1% vs. 8%, odds ratio [OR] = 0.12, 95% confidence interval [CI] = 0.01-0.95, P = 0.02); and partial pressure of arterial carbon dioxide and bicarbonate base lactate levels were similar compared with those in the control group. Upon univariate analysis, excess and absence of oxygenation treatment (OR = 9.18, CI = 1.13-74.86, P = 0.03) and anemia (OR = 4.30, CI = 1.04-17.78, P = 0.04) were shown to be associated with contrast-induced nephropathy incidence. CONCLUSION: Oxygenation, a simple, nonpharmacological strategy, may be beneficial when using contrast media in patients with impaired renal function from noninvasive angiography to emergency catheterization.

Impact of obstructive sleep apnea on clinical and angiographic outcomes following percutaneous coronary intervention in patients with acute coronary syndrome.

There has been growing evidence associating obstructive sleep apnea (OSA) with cardiovascular pathogenesis. We hypothesized that OSA may affect outcomes after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We performed a sleep study in 89 consecutive patients with ACS who were successfully treated with PCI. Patients with an apnea hypopnea index > or =10/hour were considered to have OSA. Co-morbidity of OSA with ACS was found in 51 patients (57%). There were no differences in baseline demographics between patients with and without OSA, except for significantly higher high-sensitivity C-reactive protein levels (0.59 +/- 0.75 vs 0.29 +/- 0.20 mg/dl, p = 0.019) in patients with OSA. Patients were followed for a mean period of 227 days. The incidence of major adverse cardiac events (cardiac death, reinfarction, and target vessel revascularization) was significantly higher in patients with OSA (23.5% vs 5.3%, p = 0.022). By multivariate analysis, the presence of OSA was an independent predictor for major adverse cardiac events (hazard ratio 11.61, 95% confidence interval 2.17 to 62.24, p = 0.004). In addition, quantitative coronary angiography at 6-month follow-up depicted significantly greater late loss (1.28 +/- 0.84 vs 0.69 +/- 0.81 mm, p = 0.003) and a higher binary restenosis rate (36.5% vs 15.4%, p = 0.026) in patients with OSA compared with those without OSA. In conclusion, the present study showed a high prevalence of OSA among patients with ACS. Moreover, OSA appeared to be an independent predictor for clinical and angiographic outcomes after PCI.

Coronary pressure measurement after stenting predicts adverse events at follow-up: a multicenter registry.

BACKGROUND: Coronary stenting is associated with a restenosis rate of 15% to 20% at 6-month follow-up, despite optimum angiographic stent implantation. In this multicenter registry, we investigated the relation between optimum physiological stent implantation as assessed by poststent fractional flow reserve (FFR) and outcome at 6 months. METHODS AND RESULTS: In 750 patients, coronary pressure measurement at maximum hyperemia was performed after angiographically apparently satisfactory stent implantation. Poststenting FFR was calculated and related to major adverse events (including need for repeat target vessel revascularization) at 6 months. In 76 patients (10.2%), at least 1 adverse event occurred. Five patients died, 19 experienced myocardial infarction, and 52 underwent at least 1 repeat target vessel revascularization. By multivariate analysis, FFR immediately after stenting was the most significant independent variable related to all types of events. In 36% of the patients, FFR normalized (>0.95), and event rate was 4.9% in that group. In 32% of the patients, poststent FFR was between 0.90 and 0.95, and event rate was 6.2%. In 32% of patients, poststent FFR was <0.90, and event rate was 20.3%. In 6% of the patients, FFR was <0.80, and event rate was 29.5% (P<0.001). CONCLUSIONS: FFR after stenting is a strong independent predictor of outcome at 6 months.

A large-scale prospective cohort study on the current status of therapeutic modalities for acute myocardial infarction in Japan: rationale and initial results of the HIJAMI Registry.

BACKGROUND: In Western countries, several multicenter collaborative studies on acute myocardial infarction (AMI) have provided much information about this disease. In Japan, on the other hand, there have been few cohort studies in which a sufficient number of Japanese patients with AMI were registered during a short period. This fact explains the absence of a database from which strategies for treating Japanese patients with AMI could be established. The purpose of this study was to build a comprehensive database on Japanese patients with AMI to elucidate their characteristics. METHODS: Between January 1999 and June 2001, we consecutively registered all patients with AMI who were admitted to 17 participating medical institutions, including The Heart Institute of Japan, Cardiology (HIJC), Tokyo Women's Medical University. A standardized case report form was used to register all the patients. RESULTS: A total of 3,021 consecutive patients was registered (2,136 men, 70.7%; 885 women, 29.3%) with a median age of 69 years [59, 77]. Among the patients, there were 851 elderly individuals (28.2%) > or = 76 years and 1102 patients with diabetes (36.5%). On index electrocardiogram, ST-elevation myocardial infarction was observed in 2,392 patients (79.2%). Within 24 hours after the onset of AMI, coronary angiography was conducted for 2,177 patients (72.1%). Primary percutaneous coronary intervention and coronary thrombolysis were conducted for 1,755 (58.1%) and 491 patients (16.3%), respectively, and percutaneous coronary intervention or coronary artery bypass grafting was additionally carried out in 303 patients. By the time of discharge, coronary angiography and coronary artery bypass grafting were performed in 2,659 (88.0%) and 137 patients (4.5%), respectively. During initial hospitalization, 285 patients died and the overall inhospital mortality rate was 9.4%. During hospitalization, cardiogenic shock and cardiac rupture were observed in 6.1% and 2.8% of the patients, respectively. The inhospital mortality rate is still high in patients with AMI with such mechanical complications and in elderly patients. CONCLUSION: In our prospective cohort, we showed that Japanese patients with AMI could be characterized as (1) having a disease severity comparable with values observed in Western populations and (2) receiving early reperfusion therapy by PCI, which was used widely and safely, but nevertheless (3) exhibiting a high inhospital mortality rate. Our data indicate that further improvements in therapy for AMI in elderly patients and for AMI with mechanical complications are essential in Japan.

Angiographic findings and surgical treatments of coronary artery involvement in Takayasu arteritis.

BACKGROUND: Takayasu arteritis is associated with a low incidence of coronary artery involvement, such as stenosis, obstruction, aneurysm, and coronary steal syndrome, but coronary ischemia can be fatal. METHODS: Between 1972 and April 2001, 81 of 130 patients given a diagnosis of Takayasu arteritis underwent selective coronary angiography, and among them, 31 patients (4 male and 27 female patients; mean age, 41.1 +/- 13.2 years) had abnormal coronary angiographic findings and were recruited for this study. RESULTS: Abnormal coronary findings consisted of 24 coronary artery stenoses of greater than 75%, 3 coronary artery-bronchial artery anastomoses, 3 aneurysmal coronary ectasias, and 1 combined coronary ectasia and anastomosis. Among 24 patients with coronary stenosis, the ostium was most frequently involved (87.5%). Twenty-three of 24 patients with coronary artery stenoses were treated surgically. The mean follow-up duration was 9.65 +/- 6.9 years, with a 100% follow-up rate. Four fistulas and 4 aneurysms in 7 patients were not treated surgically. Coronary steal phenomenon was always associated with occluded pulmonary arteries and pulmonary hypertension. Aneurysmal coronary ectasia was related to severe aortic hypertension with or without aortic regurgitation and atypical coarctation. There were 2 (8.7%) in-hospital deaths and 3 (13%) late deaths. The actuarial survival rate, including in-hospital deaths, was 86.5% +/- 7.3% at 5 years and 81.4% +/- 8.4% at 10 years. CONCLUSION: The incidence of coronary abnormalities is relatively low in patients with Takayasu arteritis; however, surgical treatment is recommended for patients with coronary ostial stenoses because coronary ischemia can be one of the major causes of death.

Clinical characteristics and early outcomes of very elderly patients in the reperfusion era.

BACKGROUND: Not much data is available regarding "real-world" clinical experience of very elderly patients with acute myocardial infarction (AMI) in the reperfusion era. METHODS: We reviewed 483 patients (26%) between the ages of 75 and 85 from the 1855 patients with AMI. We analyzed 264 patients treated with reperfusion therapy (55%) and 219 patients treated with conservative therapy (45%) on their clinical characteristics and early outcomes. RESULTS: Patients treated with reperfusion therapy were slightly younger (79.0 vs. 80.0 years, P=0.01), presented earlier (205 vs. 400 minutes, P<0.01) and had higher peak creatine kinase values (2634 vs. 1407 IU/l, P<0.01) than those treated with conservative therapy. Other clinical profiles including sex, prior myocardial infarction, hypertension, diabetes, and infarct location were similar to each other. There was a 92% success for reperfusion therapy. The incidence of recurrent ischemia, cardiac rupture, and cerebral hemorrhage was not significantly different between the two groups. In-hospital mortality in this study was 20.5%. In-hospital mortality was not significantly different between the two groups (19% vs. 23%, P=0.25). The multivariate analysis showed that age, infarct location, and Killip class were correlated to in-hospital mortality. The leading cause of in-hospital death was pump failure. CONCLUSIONS: Older age and late presentation were correlated to conservative therapy in very elderly patients with AMI. Early outcomes were similar between the two treatment groups. In-hospital mortality seemed to be associated with impaired myocardial reserve.

Telmisartan induces proliferation of human endothelial progenitor cells via PPARgamma-dependent PI3K/Akt pathway.

OBJECTIVE: Although recent clinical trials have suggested that angiotensin II type 1 receptor blockers (ARBs) reduced cardiovascular events, the precise mechanisms involved are still unknown. Telmisartan, an ARB, has recently been identified as a ligand of peroxisome proliferator-activated receptor-gamma (PPARgamma). On the other hand, since endothelial progenitor cells (EPCs) are thought to play a critical role in ischemic diseases, we investigated effects of telmisartan on proliferation of EPCs. METHODS AND RESULTS: Human peripheral blood mononuclear cells were isolated from healthy volunteers, and cultured on fibronectin-coated dishes in the presence or absence of telmisartan. Four days after starting culture, adherent cells were collected, and equal numbers of cells were reseeded into methylcellulose medium with or without telmisartan. In the presence of telmisartan, numbers of colonies increased in a dose-dependent manner. DiI-AcLDL uptake and lectin and CD31, CD34 staining revealed that these colonies were EPCs. Increase in colony number by treatment with telmisartan was absolutely inhibited when cultured with a specific inhibitor of PPARgamma. In addition, we observed that specific inhibitors of phosphoinositide-3 kinase (PI3K) abolished telmisartan-stimulated increase of monocytic EPC-like cells and telmisartan induced phosphorylation of Akt. Furthermore, mRNA expression of p21 was downregulated in a dose dependent manner, suggesting that growth inductive effects of telmisartan might be regulated by the PI3K/Akt and p21 signaling pathway. CONCLUSIONS: These findings suggest that telmisartan might contribute to endothelial integrity and vasculogenesis in ischemic regions by increasing numbers of EPCs.

Association of glomerular filtration rate with unsuccessful primary percutaneous coronary intervention and subsequent mortality in patients with acute myocardial infarction: from the HIJAMI registry.

BACKGROUND: Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by renal insufficiency have not been well described. The aims of this study were to evaluate the association of estimated glomerular filtration rate (GFR) and risk of unsuccessful PCI for AMI, and to evaluate the prognostic importance of PCI success in patients with renal insufficiency. METHODS AND RESULTS: From the Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry, 1,706 patients undergoing primary PCI were analyzed. The adjusted odds ratios for unsuccessful PCI of GFR 30-60 and <30 ml . min(-1) . 1.73 m(-2) were 1.97 (95% confidence interval (CI): 1.22-3.18) and 2.56 (95%CI: 1.13-5.78), respectively. During the mean follow-up period of 29 months, the adjusted hazard ratios for death of successful compared with unsuccessful PCI were 1.0 (reference) compared with 2.04 (95%CI: 0.87-4.81) in the highest GFR group, 1.51 (95%CI: 1.11-2.06) compared with 2.07 (95%CI: 1.19-3.62) in the intermediate GFR group, and 2.69 (95%CI: 1.72-4.22) compared with 10.07 (95%CI: 4.91-20.5) in the lowest GFR group. CONCLUSIONS: Decreased GFR was associated with the risk of unsuccessful primary PCI. Moreover, unsuccessful PCI was associated with strikingly poor long-term survival in patients with GFR <30 ml .min(-1) . 1.73 m(-2). Steady success is essential when using PCI for such a high-risk population.

Primary percutaneous coronary intervention vs conservative treatment for acute ST elevation myocardial infarction: short- and long-term follow-up according to disease severity.

BACKGROUND: Because there is insufficient evidence to support primary percutaneous coronary intervention (PPCI) as the treatment of acute myocardial infarction (AMI), this study elucidated the efficacy of PPCI according to disease severity. METHODS AND RESULTS: Between January 1999 and June 2001, 3,021 AMI patients were registered at Tokyo Women's Medical University and 17 affiliated institutions. Of these, 1,994 patients with ST-elevation AMI were admitted within 12 h of onset. PPCI was performed in 1,143 and 294 were treated conservatively. The 1,437 patients were grouped according to Thrombolysis In Myocardial Infarction-risk score: PPCI was performed in 59.5% of the low-risk group, 61.8% of the moderate-risk group, and 56.2% of the high-risk group. Cardiac death was the primary outcome. In the low-risk group, no significant differences were observed between PPCI and conservative therapy for 30-day and long-term cardiac mortality rates. In the moderate-risk group, the 30-day cardiac mortality rate for PPCI was significantly lower; however, no significant intergroup differences were observed for long-term cardiac mortality. In the high-risk group, 30-day and long-term cardiac mortality for PPCI were significantly more favourable than for conservative therapy (p<0.001 and p=0.0032, respectively). CONCLUSIONS: Although PPCI strongly correlated with low short- and long-term cardiac mortality rates in high-risk AMI patients, no similar correlation was found in low-risk patients.

Noninvasive prediction of angiographic spasm provocation using trans-thoracic Doppler echocardiography in patients with coronary spastic angina.

BACKGROUND: In the present study it was examined whether transthoracic Doppler echocardiography (TTDE) would be useful for noninvasive diagnosis of coronary spastic angina (CSA) by assessing coronary arterial tone in the morning. METHODS AND RESULTS: The study population comprised 21 CSA patients and 27 control subjects. All diagnoses were angiographically confirmed by provocation test using acetylcholine. Coronary flow velocity reserve (CFVR) was measured at the distal left anterior descending artery with a frequency of 5.0 MHz ultrasound at baseline and after sublingual administration of nitroglycerin (NTG). Coronary arterial tone was assessed by obtaining the change of CFVR induced by NTG administration (CFVR(NTG/Pre)). Basal CFVR tended to be lower in CSA patients (2.13+/-0.63, 2.71+/-0.67, respectively, p = 0.05). CFVR after NTG was significantly higher in CSA patients (3.91+/-1.10, 3.07+/-0.74, p = 0.003). The CFVR(NTG/Pre) was significantly higher in CSA patients than in the control subjects (1.90+/-0.49, 1.15+/-0.22, p < 0.0001). Using a cut-off value of 1.4 in CFVR(NTG/Pre), the sensitivity and specificity for the diagnosis of CSA were 91% and 90%, respectively. CONCLUSION: TTDE appeared to be useful for the noninvasive diagnosis of CSA by assessing the coronary arterial tone.

Utility of multislice computed tomography as a strategic tool for complex percutaneous coronary intervention.

OBJECTIVES: Multislice computed tomography (MSCT) has been currently utilized as a non-invasive diagnostic modality to detect coronary artery disease. We sought to investigate whether preprocedural lesion assessment by MSCT could offer strategic guidance in the setting of elective complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: Twenty-six complex coronary artery lesions in 23 patients were evaluated using 16-row MSCT scanner and an off-line image analysis workstation prior to the PCI. Procedural strategies of PCI were planned based on the morphologic and geometric analysis of the target lesion and vessel. MSCT provided valuable strategic information, which was useful for subsequent PCI procedure. The three-dimensional computed tomography (CT) images allowed us to determine optimal working view angle that best demonstrated the target lesion with least foreshortening. Furthermore, the thin-slab maximum intensity projected CT images of the target lesion served as a preprocedural road map depicting the bends of complex luminal path, vessel geometry and occluded segment of the vessel. As results, procedural success was achieved in all cases with complex lesions including chronic total occlusion. CONCLUSIONS: Our preliminary results showed that preprocedural lesion and vessel assessment by MSCT provided important additive strategic information that led to successful complex PCI procedures.

Impact of post-dilatation with a focal expanding balloon for optimization of intracoronary stenting.

Optimal stenting frequently requires additional stent post-dilatation following initial stent deployment. Stent post-dilatation using a focal expanding balloon (FB) that grows 0.5 mm larger centrally may achieve a larger final stent lumen with fewer stent edge injuries as compared to use of a conventional unidiameter balloon (UB). In the present prospective study, of 128 stented lesions in 122 patients, 63 lesions had stents dilated with FB (Group F), while 65 lesions had stents dilated with UB (Group U). All balloons for stent post-dilatation were half-sized up to reference diameter by on-line quantitative coronary analysis. There were no differences in the reference diameter, pre-procedural minimal lumen diameter (MLD), balloon/artery ratio, and final balloon pressure between the two groups. Post-procedural MLD in Group F was significantly larger than that in Group U (3.03 +/- 0.43 vs 2.80 +/- 0.47 mm, P < 0.001). Stent edge injury occurred in 4 patients, and stent thrombosis in 2 patients in Group U, but not in Group F. Minimal lumen diameter at 6 months in Group F was significantly larger than that in Group U (2.05 +/- 0.63 vs 1.82 +/- 0.66 mm, P < 0.05), and incidence of restenosis was significantly lower in Group F than Group U (9% vs 22%, P < 0.05). By using a focal expanding balloon for stent optimization, a larger stent lumen can be obtained safely, and subsequent incidence of restenosis can be reduced.

High P-selectin expression and low CD36 occupancy on circulating platelets are strong predictors of restenosis after coronary stenting in patients with coronary artery disease.

Recent studies have shown that circulating platelets play an important role in the development of restenosis early after coronary stent implantation. We investigated P-selectin expression and CD36 blockade on platelets by flow cytometry in 48 consecutive patients who underwent coronary stenting. P-selectin expression was significantly higher 1 day after stenting in patients who had restenosis (n = 15) than in those who had no restenosis (n = 28), and the odds ratio for restenosis in patients with high P-selectin levels (MFI > 6.5) was 11.67 (P < 0.001) as compared with patients who had intermediate and low P-selectin levels. CD36 blockade was assessed with the use of two anti-CD36 antibodies, OKM5 and GS95 (our new anti-CD36 antibody), the binding of which indicates total CD36 amount and free CD36 unoccupied by lipid-related ligands, respectively. Binding of OKM5 to platelets was similar before and after stenting in both groups. CD36 blockade on platelets was seen 1 day after stenting in the non-restenosis group, and the odds ratio for restenosis in patients without CD36 blockade [GS95 binding ratio >0.8 as compared with binding before stenting] on day 1 was 28.60 (P < 0.001). P-selectin expression and unoccupied CD36 on platelets shortly after stenting may be strong predictors of post-stent restenosis.

Postprocedural resistance of the target lesion is a strong predictor of subsequent revascularization: assessment by a novel lesion-specific physiological parameter, the epicardial resistance index.

Objective evaluation of the functional significance of individual stenosis in patients with multiple lesions is crucial when performing percutaneous coronary intervention (PCI). Here we propose a novel lesion-specific parameter, the epicardial resistance index (ERI), which is derived from intracoronary pressure measurements, and validate its clinical usefulness. The ERI is defined as the ratio of the resistance of an epicardial coronary stenosis to that of downstream myocardium. After obtaining intracoronary pressure data by pull-back of a 0.014'' pressure wire, the ERI was calculated as the trans-lesional pressure gradient divided by (Pd-Pv) at maximum hyperemia, where Pd = the mean distal coronary pressure in the absence of any stenosis and Pv = the central venous pressure. Using 170 measurements obtained from 75 patients, the correlation of ERI with parameters obtained from quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) was studied. ERI showed a significant correlation with the QCA-derived percent diameter stenosis (r = 0.67, P < 0.001), and with the IVUS-derived minimum luminal area (r = 0.68, P < 0.001). In 55 patients who underwent PCI with bare metal stents, a postprocedural target lesion ERI value greater than 0.16 strongly predicted the need for subsequent revascularization within six months (81% sensitivity and 80% specificity). The ERI is a useful pressure-derived hemodynamic parameter that correlates with anatomical parameters. In addition, the postprocedural resistance of the target lesion indicated by the ERI is a reliable predictor of the late outcome of PCI.

[Prognostic value of C-reactive protein and troponin T level in patients with unstable angina pectoris].

OBJECTIVES: The prognosis of unstable angina pectoris may be more accurately predicted by the combination of C-reactive protein (CRP), which is a known inflammation marker, and troponin T (TnT), which is used for risk assessment for the prognosis of acute coronary syndrome. The present study investigated the correlations between pathophysiology and prognosis of severe unstable angina pectoris and CRP and TnT levels. METHODS: The correlation between CRP at admission and the prognosis was studied in 367 patients with severe unstable angina pectoris (Braunwald type II and III) who were admitted to our hospital between January 1998 and December 2000. The in-hospital and long-term prognosis was investigated in TnT-positive patients. In-hospital cardiac events were defined as death, myocardial infarction, heart failure and angina attacks during hospitalization. Long-term cardiac events were defined as death, myocardial infarction, heart failure and recurrence of angina. RESULTS: The incidence of in-hospital cardiac events in all patients was 30.2%. The CRP levels were higher in patients with cardiac events (0.97 +/- 2.67 vs 0.53 +/- 1.29 mg/d/, p = 0.057), but there was no significant difference between the two groups. The incidence of long-term cardiac events was 26.8%. The mean CRP level was significantly higher in patients with cardiac events than in patients without cardiac events (1.17 +/- 1.86 vs 0.43 +/- 1.14 mg/dl, p = 0.098). In TnT-positive patients (TnT > 0.1 ng/ml, 23% of all patients), the incidence of in-hospital cardiac events was 47.6% (p < 0.0001), significantly higher than that in all patients. TnT-positive patients with CRP levels of 0.5 mg/dl or higher (8% of all patients) had a markedly higher incidence of in-hospital cardiac events of 56.7% (p = 0.001) and long-term cardiac events of 46.7% (p = 0.01). CONCLUSIONS: CRP levels were useful in prediction of the long-term prognosis. TnT levels were useful in prediction of in-hospital prognosis. The present study suggested the possibility that the combined use of these biological markers could predict the prognosis of patients with unstable angina at early stage and more accurately.