Impact of chronic kidney disease on the incidence of peri-procedural myocardial injury in patients undergoing elective stent implantation.

BACKGROUND: It is well known that chronic kidney disease is a strong independent predictor of adverse outcomes after percutaneous coronary intervention in patients with ischemic heart disease. Recently, peri-procedural myocardial injury has been associated with adverse cardiac events. The aim of this study was to investigate the relationship between renal function and peri-procedural myocardial injury in patients undergoing elective stent implantation. METHODS: This study comprised 273 consecutive patients who underwent elective stent implantation. They were divided into two groups: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m(2) and eGFR ≥60 mL/min/1.73m(2). Peri-procedural TnT levels higher than three times the normal limit were defined as peri-procedural myocardial injury. RESULTS: Patients with eGFR <60 mL/min/1.73m(2) showed a higher incidence of peri-procedural myocardial injury compared to patients with eGFR ≥60 mL/min/1.73m(2) (4.3 versus 20.9%, P < 0.0001). Even after a multivariate adjustment, the eGFR level predicted peri-procedural myocardial injury [odds ratio 0.92, 95% confidence interval (CI): 0.89-0.95, P < 0.0001]. Total stent length was also an independent predictor of peri-procedural myocardial injury (odds ratio 1.09, 95% CI: 1.02-1.16, P = 0.009). Using a receiver-operating curve analysis, eGFR level of 62.1 mL/min/1.73m(2) (sensitivity 93.3%, specificity 57.2%) was the best value (area under the curve = 0.803) to maximize the power of eGFR levels in predicting peri-procedural myocardial injury. CONCLUSIONS: Patients with eGFR <60 mL/min/1.73m(2) were strongly associated with peri-procedural myocardial injury after elective stent implantation. Therefore, eGFR may be a simple and convenient predictor of peri-procedural myocardial injury.

Lipid-rich plaques predict non-target-lesion ischemic events in patients undergoing percutaneous coronary intervention.

BACKGROUND: Despite growing interest in non-target lesion events in patients undergoing percutaneous coronary intervention (PCI), there has been little discussion of predictors. METHODS AND RESULTS: A total of 155 consecutive patients who underwent PCI were enrolled. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) parameters were measured in non-target lesions utilizing a 40-MHz intravascular catheter. Lipid-rich plaques (LRP) were defined as lesions with an increased lipid volume (> median) and greater lipid content. Non-target ischemic events were defined as death, non-fatal myocardial infarction, any repeat revascularization and rehospitalization for angina involving the non-target vessel or the target vessel outside the index lesion. During the follow-up period (median: 1,265 days), non-target events were observed in 16 patients (11%). Using the Cox proportional hazard model, LRP (odds ratio [OR], 6.06; 95% confidence interval [CI]: 1.81-20.4, P = 0.0035), elevated serum C-reactive protein (CRP) levels (OR, 6.83; 95%CI: 2.19-21.3, P = 0.0009) and acute coronary syndrome present at baseline (OR, 4.08; 95%CI: 1.21-13.8, P = 0.024) were significantly and independently associated with non-target events. Synergistic effects of LRP and elevated serum CRP levels for prediction of non-target events (OR, 14.8; 95%CI: 4.57-48.0, P < 0.0001) were found even after adjusting for confounders. CONCLUSIONS: LRP measured using IB-IVUS proved to be an independent morphologic predictor of non-target ischemic events after PCI, particularly enhancing the risk in patients with elevated serum CRP levels.

Trends in physiological coagulation factors in Japanese patients receiving novel oral anticoagulants.

BACKGROUND: Little is known about physiological anticoagulation effects via antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral anticoagulants (NOACs). METHODS: We evaluated 120 consecutive patients with non-valvular atrial fibrillation (AF) receiving NOACs. Patients were randomly divided into three groups: a dabigatran group (DG, N=40), a rivaroxaban group (RG, N=40) or an apixaban group (AG, N=40). A warfarin group (WG, N=40) was matched with NOAC groups for age, sex and type of AF during the same time period. Blood samples were obtained in pretreatment, trough and peak phases to measure the activity of physiological coagulation inhibitors, including AT III and PC/PS or thrombus formation markers such as D-dimer and thrombin-antithrombin complex (TAT). RESULTS: D-dimer, TAT and AT III values for the NOAC groups were equivalent in the peak and trough phases. PC/PS activity in both phases was equally maintained in the pretreatment phase in the NOAC groups, while the activity in the WG was significantly suppressed in steady state. Moreover, no differences in trends for PC/PS activity were observed among NOAC groups. CONCLUSIONS: PC/PS activity was constant in both peak and trough phases in the patients on NOACs compared with activity of those on warfarin. In addition, there was no difference in the findings among NOACs.

Increased expression of the adipocytokine omentin in the epicardial adipose tissue of coronary artery disease patients.

BACKGROUND AND AIMS: Omentin, an adipocytokine secreted by visceral adipose tissue, protects against obesity-linked cardiovascular complications. However, little is known about its role in epicardial adipose tissue (EAT) and coronary artery disease (CAD). We investigated the expression of omentin in EAT from CAD subjects. METHODS: EAT, subcutaneous adipose tissue (SCAT), and plasma samples were collected from CAD (n = 15; 23.3 ± 3.1 kg/m(2)) and non-CAD patients (n = 10; 20.8 ± 3.9 kg/m(2)). Omentin mRNA expression was measured using real-time PCR, while plasma concentrations were measured using an ELISA. EAT volume was determined with 64-slice computed tomography. RESULTS: Omentin expression in EAT and EAT volume were higher in CAD patients compared with controls (2.49 ± 2.6 vs. 0.85 ± 0.3, p = 0.002 and 113 ± 58 ml vs. 92.4 ± 30 ml, p = 0.045, respectively). Omentin expression in SCAT was similar between CAD and control patients (1.37 ± 0.84 vs. 1.07 ± 0.55, p = 0.267). Plasma omentin levels were lower in CAD patients compared with controls (343 ± 158 ng/ml vs. 751 ± 579 ng/ml, p = 0.025), and were negatively associated with the expression of omentin in EAT, in patients with CAD (ß = -0.78, p = 0.049). On the other hand, there was no association between omentin in EAT and clinical variables in patients with non-CAD. CONCLUSIONS: Omentin expression increases in the EAT of non-obese CAD patients, despite a decrease in plasma levels, suggesting that omentin may play a role in the pathogenesis of CAD.

Prognostic Value of Albuminuria on Cardiovascular Outcomes After Elective Percutaneous Coronary Intervention.

Albuminuria is the most widely evaluated marker of kidney damage. Many previous studies have demonstrated an association between the presence of albuminuria and increased cardiovascular events. However, there are limited data regarding the impact of albuminuria in patients requiring coronary revascularization. This study investigated whether the urinary albumin excretion rate could predict cardiovascular events in such a population. We enrolled 698 consecutive patients who underwent elective percutaneous coronary intervention. The baseline urinary albumin-to-creatinine ratio (ACR; mg/gCr) was measured and patients were divided into those with normoalbuminuria (ACR <30 mg/gCr), microalbuminuria (ACR 30 to 300 mg/gCr), or macroalbuminuria (ACR >300 mg/gCr). We collected data on the incidences of cardiac death and/or nonfatal myocardial infarction. We identified 389, 230, and 79 patients with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively. During follow-up (median: 1,564 days), 41 events occurred. The event-free survival rate was 89% in patients with macroalbuminuria, 92% in those with microalbuminuria, and 97% in those with normoalbuminuria, respectively (log-rank test p = 0.002). After adjustment for conventional risk factors, Cox analysis revealed hazard ratios for cardiac death and/or nonfatal myocardial infarction were 2.56 (95% CI 1.23 to 5.32, p = 0.01) in those with microalbuminuria and 4.02 (95% CI 1.59 to 10.12, p = 0.003) in those with macroalbuminuria compared with those with normoalbuminuria. In conclusion, an elevated urinary albumin excretion rate independently predicted adverse cardiovascular outcomes, with a gradual risk increase that progressed from microalbuminuria to macroalbuminuria in patients undergoing elective percutaneous coronary intervention.

Long-term treatment with low-dose, but not high-dose, guanethidine improves ventricular function and survival of rats with heart failure after myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of various doses of guanethidine, a sympathoinhibitory drug, on ventricular function and survival in chronic heart failure (CHF) after myocardial infarction (MI) in rats. BACKGROUND: Direct inhibition of sympathetic outflow by a sympathoinhibitory drug might be an effective approach to therapy of CHF. However, recent clinical trials suggest that excessive suppression of sympathetic activity has an adverse effect on outcome. It remains unclear whether the beneficial effects of the sympathoinhibitory drug would be modified by its dosage. METHODS: Three doses of guanethidine (low-dose [LG], 1 mg/kg/day; medium-dose, 3 mg/kg/day; high-dose, 10 mg/kg/day) were administered via an osmotic mini-pump for 4 weeks. Hemodynamics, left ventricular (LV) diameters, plasma and myocardial norepinephrine (NE) levels, and survival were determined for four weeks after MI. RESULTS: As compared with MI rats receiving vehicle, LG suppressed LV dilation (9.2 +/- 0.9 mm vs. 11.0 +/- 0.8 mm, p < 0.05) and improved LV fractional shortening (25.0 +/- 4.5% vs. 16.4 +/- 4.7%, p < 0.05) in association with a reduction of plasma NE levels (520 +/- 250 pg/ml vs. 1,000 +/- 570 pg/ml, p < 0.05), but not with a significant reduction of noninfarcted myocardial NE levels (154 +/- 71 ng/g vs. 207 +/- 71 ng/g). Low-dose guanethidine reduced 24-h (6%) and 28-day mortality (6%), as compared with untreated MI rats (36% and 52%, respectively). High-dose guanethidine also reduced 24-h mortality (12%) but increased 28-day mortality (91%), in association with a depletion of myocardial NE. Medium-dose guanethidine had no beneficial effects on LV hemodynamics or long-term survival. CONCLUSIONS: These results indicate that the dosage of the sympathoinhibitory drug might be quite important for the treatment of CHF.

Evaluation of fatty acid metabolism in hearts after ischemia-reperfusion injury using a dual-isotope autoradiographic approach and tissue assay for metabolites of tracer.

UNLABELLED: We investigated whether changes in myocardial uptake of fatty acid tracer after reperfusion following transient myocardial ischemia were closely related to alterations in intracellular fatty acid oxidation. METHODS: Using a fatty acid tracer of (131)I- and (125)I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), the myocardial uptake and metabolites were determined by dual-tracer autoradiography and thin-layer chromatography in rats 3 or 14 d after reperfusion following 5 or 15 min of ischemia induced by coronary artery ligation. RESULTS: 9MPA metabolites processed via beta-oxidation were lower in the ischemic region (IR) than in non-IR 3 d after 5 min of ischemia, despite no reduction of tracer uptake in IR. Oxidation of 9MPA was recovered 14 d after 15 min of ischemia in association with normalization of tracer uptake in IR, whereas both uptake and oxidation of 9MPA were markedly impaired 3 d after 15 min of ischemia, accompanied by slow clearance of myocardial tracer. CONCLUSION: Normal uptake of fatty acid tracer early after reperfusion does not always imply preserved intracellular fatty acid oxidation. However, reduction of tracer uptake might reflect impaired fatty acid oxidation.

Discrepant recovery course of sympathetic neuronal function and beta-adrenoceptors in rat hearts after reperfusion following transient ischemia.

UNLABELLED: Cardiac sympathetic neuronal function is closely coupled with beta-adrenoceptors and adrenergic signaling. However, the recovery process of sympathetic neuronal function and beta-adrenoceptors after reperfusion following transient ischemia is not fully understood. Accordingly, this study was performed to investigate serial changes in sympathetic neuronal function and beta-adrenoceptors after transient myocardial ischemia. METHODS: The left coronary artery of male Wister rats was ligated for 15 min followed by reperfusion. A dual-tracer method of (131)I-metaiodobenzylguanidine ((131)I-MIBG) and (125)I-iodocyanopindolol ((125)I-ICYP) was used to assess cardiac sympathetic neuronal function and beta-adrenoceptor density on days 1, 3, 7, 14, and 28 after reperfusion. Myocardial norepinephrine (NE) content in ischemic regions (IR) and in remote regions (RR) and hemodynamic indices were determined. Using a membrane preparation of the rat heart after reperfusion, the maximum specific binding (B(max)) of beta-adrenoceptors was compared with (125)I-ICYP accumulation. RESULTS: The maximum value of the rate of change in left ventricular (LV) pressure (dP/dt(max)) tended to decrease on day 1 after reperfusion but recovered thereafter. Myocardial NE content was significantly reduced in IR compared with RR on day 1 (272 +/- 49 vs. 487 +/- 93 ng/g, P < 0.01), and the decrease became more severe on day 14 (36 +/- 19 vs. 489 +/- 132 ng/g, P < 0.01) and day 28 (37 +/- 14 vs. 455 +/- 216 ng/g, P < 0.01). Decrease in the IR-to-RR uptake ratio of (131)I-MIBG was modest on day 1 (0.64 +/- 0.12) and became more severe on days 7 and 14 (0.38 +/- 0.12 and 0.35 +/- 0.13, respectively). This reduction was partially restored on day 28 (0.50 +/- 0.18). In contrast, the IR-to-RR uptake ratio of (125)I-ICYP was severely decreased until day 3 (0.60 +/- 0.13 on day 1 and 0.54 +/- 0.19 on day 3) and recovered thereafter. On day 3, B(max) was significantly lower in IR than in RR (83 +/- 17 vs. 100 +/- 12 fmol/mg, P < 0.05), but the dissociation constant did not differ between the 2 regions. CONCLUSION: The recovery course of cardiac (131)I-MIBG uptake after reperfusion following transient ischemia is quite different from that of (125)I-ICYP. Simultaneous scintigraphic portrayal of beta-adrenoceptors together with (131)I-MIBG would provide useful information regarding adrenergic system signaling in patients with coronary artery disease.

Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients.

OBJECTIVE: Ectopic fat accumulation is associated with coronary artery disease. Visceral adipose tissue has paracrine and systemic effects and is a source of adipocytokines. It has been implicated in the pathogenesis of coronary atherosclerosis; however, nothing is known about whether increases in epicardial fat have the same effect on coronary atherosclerosis as increases in abdominal visceral fat. METHODS: We examined 216 consecutive patients suspected to have coronary artery disease. Individuals with acute coronary syndrome and inadequate computed tomography (CT) imaging were excluded. We enrolled 164 patients (65 ± 10 years old; 70% men; body mass index [BMI], 23.8 ± 3.6 kg/m(2)). The plasma concentrations of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. The characteristics of coronary plaque, abdominal visceral fat area, and epicardial fat volume (EFV) were determined by 64-slice CT imaging. RESULTS: EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 mL vs. 98 ± 34 mL and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, triglycerides, and the triglyceride/high-density lipoprotein cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma levels of adipocytokines. The plasma adiponectin and IL-6 concentration was significantly correlated with abdominal visceral fat area in coronary plaque patients (r = -0.49 and 0.20). CONCLUSIONS: In non-obese Japanese patients, epicardial fat may have unique mechanisms affecting the development of coronary atherosclerosis, which is different from abdominal visceral fat.

The different association of epicardial fat with coronary plaque in patients with acute coronary syndrome and patients with stable angina pectoris: analysis using integrated backscatter intravascular ultrasound.

OBJECTIVES: We assessed the hypothesis that the epicardial fat is associated with coronary lipid plaque. BACKGROUND: Epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS), and lipid-rich plaques have been associated with acute coronary events. METHODS: We enrolled 112 individuals who underwent percutaneous coronary intervention (PCI) (66 with ACS; 46 with stable angina pectoris [SAP]) and classified plaque components using integrated backscatter intravascular ultrasound as calcified, fibrous, or lipid. Possible effects of PCI on plaque data were minimized by assessing 10-mm vessel lengths proximal to the culprit lesions. Total plaque volume and percentage volumes of individual plaque components were calculated. EFV and abdominal visceral fat area were measured using 64-slice computed tomography. RESULTS: ACS patients had significantly higher EFV than did SAP patients (118 ± 44 vs.101 ± 41 mL, p = 0.019). In ACS patients, EFV was correlated with total plaque volume and percentage of lipid plaque (r = 0.27 and 0.31, respectively; p < 0.05). Moreover, an independent interaction between EFV and lipid-rich plaque (odds ratio, 1.04; 95% confidence interval, 1.00-1.07) were revealed. In contrast, in SAP patients, EFV was positively correlated with body mass index and abdominal visceral fat area but not with plaque characteristics. CONCLUSIONS: EFV was associated with lipid-rich plaque in patients with ACS, whereas no correlation between EFV and coronary plaque profile was apparent in SAP patients. Epicardial fat may have a role in the development of lipid plaque, which contributes to the pathogenesis of ACS.

Association of inflammatory markers with the morphology and extent of coronary plaque as evaluated by 64-slice multidetector computed tomography in patients with stable coronary artery disease.

We evaluated the association between inflammatory markers and coronary artery plaque assessed by 64-slice multidetector computed tomography. Coronary computed tomography angiography was performed in patients with chest discomfort suggestive of coronary artery disease (CAD). Individuals with an acute coronary syndrome were excluded from the study. Coronary plaque morphology, the number of artery segments exhibiting plaque, and the number of vessels with >50% stenosis were evaluated. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. Among the 178 patients studied (age 65 ± 10 years; 70% men), 125 were diagnosed with CAD. Hs-CRP and IL-6 concentrations were significantly higher in patients with CAD than in patients without (2.73 ± 4.7 vs. 1.32 ± 2.6 mg/L, P = 0.018, and 3.06 ± 3.3 vs. 2.19 ± 2.4 pg/mL, P = 0.036). The IL-6 level was high in patients with predominantly calcified plaque, and was significantly higher in patients with 4-9 plaque segments than in those with no or 1-3 plaque segments (4.07 ± 5.3 vs. 2.19 ± 2.4 pg/mL and 2.43 ± 2.0 pg/mL, respectively, P = 0.025). The number of stenotic vessels was not significantly related to inflammatory markers. Multivariate logistic analysis revealed that plasma levels of hs-CRP but not IL-6 were associated with the presence of coronary plaque with calcification (OR 3.37, P = 0.026). This study supports the usefulness of inflammatory markers for the evaluation of coronary plaque in patients with stable CAD.

Prognostic impact of concurrence of metabolic syndrome and chronic kidney disease in patients undergoing coronary intervention: Involvement of coronary plaque composition.

BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) and chronic kidney disease (CKD) have both been reported as risk factors for cardiovascular events. The aim of this study was to assess the synergistic effect of MetS and CKD on atherosclerotic plaque and cardiovascular outcomes. METHODS AND SUBJECTS: A total of 545 consecutive patients who underwent percutaneous coronary intervention (PCI) were divided into 4 groups based on the presence or absence of MetS and CKD. MetS was defined using the criteria of the Adult Treatment Panel III of the US National Cholesterol Education Program. CKD was defined as an estimated glomerular filtration rate of <60ml/min/1.73m(2). We analyzed the incidence of major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, and revascularization for new lesions. We also assessed coronary plaque characteristics of 204 patients using integrated backscatter intravascular ultrasound (IB-IVUS). RESULTS: MACE occurred more frequently in patients with both MetS and CKD (51.4%) than in the other groups, during the follow-up period (log-rank p<0.001). In the IB-IVUS analyses, patients with both MetS and CKD exhibited greater plaque burden (p=0.003) with higher lipid content (p=0.048) compared to the other groups. In Cox analysis, both MetS and CKD proved to be independent predictors of MACE even after adjustment for confounding factors (p=0.018). CONCLUSIONS: Comorbidity of MetS and CKD is an independent predictor of adverse cardiovascular outcomes in patients undergoing coronary intervention, an effect that may be attributed to coronary plaque instability.

Differences in tissue characterization of restenotic neointima between sirolimus-eluting stent and bare-metal stent: integrated backscatter intravascular ultrasound analysis for in-stent restenosis.

AIMS: The pathogenesis of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The purpose of this study is to analyse tissue characterizations of neointima in restenosis lesions after sirolimus-eluting stent (SES), comparing with those after bare metal stent (BMS) using integrated backscatter intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: A total of 54 consecutive patients who had ISR lesions after SES (n = 20) or BMS (n = 34) implantation were enrolled. For tissue characterization of neointima, IB-IVUS was performed by cross-sectional (at the minimum lumen area) and volumetric (within the stented segment) analyses. In addition, angiographic patterns of restenosis were evaluated with division into focal and diffuse. The focal angiographic pattern of restenosis was predominantly observed in the SES group (SES vs. BMS; 80.0 vs. 26.5%; P = 0.0001), whereas the diffuse pattern was more common in the BMS group (SES vs. BMS; 20.0 vs. 73.5%; P = 0.0001). On both cross-sectional and volumetric IB-IVUS analyses, the neointimal tissue in restenosis lesions after SES implantation had a significantly larger percentage of lipid tissue (cross-sectional: 23.3 ± 12.7 vs. 15.7 ± 11.9%; P = 0.033; volumetric: 22.8 ± 10.4 vs. 16.3 ± 7.0%; P = 0.008) and a significantly smaller percentage of fibrous tissue compared with that after BMS implantation (cross-sectional: 73.6 ± 11.6 vs. 82.0 ± 11.2%; P = 0.011, volumetric: 73.8 ± 9.5 vs. 80.5 ± 6.7%; P = 0.004). CONCLUSION: This IB-IVUS study indicates that larger amounts of lipid tissue are present in neointima of SES when compared with BMS, suggesting that neoatherosclerosis may in part be responsible for ISR after SES implantation.

Impact of insulin resistance on post-procedural myocardial injury and clinical outcomes in patients who underwent elective coronary interventions with drug-eluting stents.

OBJECTIVES: This study sought to evaluate the associations between homeostatic indexes of insulin resistance (HOMA-IR) and post-procedural myocardial injury and clinical outcome after a percutaneous coronary intervention (PCI) with a drug-eluting stent. BACKGROUND: Insulin resistance increases the risk of cardiovascular events. However, the association between insulin resistance and clinical outcome after coronary intervention is unclear. METHODS: We evaluated 516 consecutive patients who underwent elective PCI with drug-eluting stents. Blood samples were collected from venous blood after overnight fasting, and fasting plasma glucose and insulin levels were measured. HOMA-IR was calculated according to the homeostasis model assessment. Post-procedural myocardial injury was evaluated by analysis of troponin T and creatine kinase-myocardial band isozyme levels hours after PCI. Cardiac event was defined as the composite endpoint of cardiovascular death, myocardial infarction, and any revascularization. RESULTS: With increasing tertiles of HOMA-IR, post-procedural troponin T and creatine kinase-myocardial band levels increased. In the multiple regression analysis, HOMA-IR was independently associated with troponin T elevation. During a median follow-up of 623 days, patients with the highest tertiles of HOMA-IR had the highest risk of cardiovascular events. The Cox proportional hazard models identified HOMA-IR as independently associated with worse clinical outcome after adjustment for clinical and procedural factors. CONCLUSIONS: These results indicated the impact of insulin resistance on post-procedural myocardial injury and clinical outcome after elective PCI with drug-eluting stent deployment. Evaluation of insulin resistance may provide useful information for predicting clinical outcomes after elective PCI.

Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: an integrated backscatter intravascular ultrasound study.

OBJECTIVE: To assess the impact of omega-3 polyunsaturated fatty acids (ω3 PUFAs) on coronary plaque instability. METHODS: Serum content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) was measured in 336 of 368 consecutive patients suspected of having coronary artery disease who underwent coronary angiography. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) parameters were analyzed in 116 patients with 128 coronary plaques, using a 43-MHz (motorized pullback 0.5mm/s) intravascular catheter (View It, Terumo Co., Japan). Lipid-rich plaques were classified into two categories according to their components. RESULTS: Patients with acute coronary syndrome had significantly lower levels of ω3 PUFAs (especially of EPA and DPA) than those without it. IB-IVUS analyses showed that ω3 PUFAs correlated inversely with % lipid volume and positively with % fibrous volume. Patients with low EPA levels, low DPA levels, and low DHA levels had a significantly higher % lipid volume (p=0.048, p=0.008, and p=0.036, respectively) and a significantly lower % fibrous volume (p=0.035, p=0.008, and p=0.034, respectively) than those with high levels of these fatty acids. Even after adjustment for confounders, the presence of both low EPA and low DPA levels proved to be an independent predictor for lipid-rich plaques in any of the two categories. CONCLUSIONS: A lower serum content of ω3 PUFAs (especially of EPA and DPA) was significantly associated with lipid-rich plaques, suggesting the contribution to the incidence of acute coronary syndrome.

Cardiac 64-multislice computed tomography reveals increased epicardial fat volume in patients with acute coronary syndrome.

Inflammatory cytokines released from epicardial fat around coronary arteries may modulate the coronary arteries and promote coronary atherosclerosis. We assessed the hypothesis that epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS). EFV was measured in 80 Japanese patients hospitalized for ACS using 64-multislice computed tomography. The ACS group included 51 patients with ST-segment elevated myocardial infarction and 29 patients with non-ST-segment elevated myocardial infarction. All patients underwent emergency coronary angioplasty and 64-multislice computed tomographic scanning during hospitalization. The control group included 90 consecutive outpatients with suspected ACS whose coronary computed tomographic results were normal. EFV was larger in patients with ACS than in the control group (117 ± 47 vs 95 ± 33 ml, p <0.001). Multivariate regression analysis showed that EFV was associated with age, body mass index, and visceral fat area in the control group. However, these correlations did not appear in the ACS group. Multivariate logistic regression analysis showed that EFV >100 ml was independently associated with ACS (odds ratio 2.84, 95% confidence interval 1.17 to 6.87, p = 0.021). Receiver operator characteristic analysis determined a cut-off value of 100.3 ml with a sensitivity of 75% and a specificity of 60% for ACS (area under the curve 0.692, 95% confidence interval 0.596 to 0.777, p <0.001). Compared to subcutaneous adipose tissue, epicardial adipose tissue showed inflammatory cell infiltrates on a micrograph. In conclusion, the present study demonstrated significantly increased EFV in patients with ACS. A large amount of epicardial fat may be a risk factor for ACS.

The association between plaque characterization by CT angiography and post-procedural myocardial infarction in patients with elective stent implantation.

OBJECTIVES: This study sought to evaluate the association between volumetric characterization of target lesions by multidetector computed tomography (MDCT) angiography and the risk of post-procedural myocardial injury after elective stent implantation. BACKGROUND: Previous reports have shown that plaque characterization of the target lesion may provide useful information for stratifying the risk of coronary stenting. METHODS: A total of 189 consecutive patients were enrolled; they underwent elective stent implantation after volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50 HU); 2) moderate-attenuation plaque (MAP) (50 to 150 HU); 3) lumen (151 to 500 HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque component in the target lesion was calculated using Color Code Plaque. Post-procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 h after percutaneous coronary intervention were also evaluated. RESULTS: The volumes of LAP (87.9+/-94.8 mm3 vs. 47.4+/-43.7 mm3, p<0.01) and MAP (111.6+/-77.5 mm3 vs. 89.8+/-67.1 mm3, p<0.05) were larger in patients with post-procedural myocardial injury (defined as positive TnT) than in those with negative TnT. The volumes of LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume) correlated with biomarkers; the MAP fraction was inversely correlated with biomarkers. The volume of LAP was an independent predictor of positive TnT after adjusting for patient background, conventional IVUS parameters, and procedural factors. CONCLUSIONS: Post-procedural myocardial injury was associated with the volume and fraction of LAP as detected by MDCT. The volume of LAP was an independent predictor of positive TnT. Plaque analysis by MDCT would be a useful method for predicting post-procedural myocardial injury after percutaneous coronary intervention.

Intracoronary electrocardiogram recording with a bare-wire system: perioperative ST-segment elevation in the intracoronary electrocardiogram is associated with myocardial injury after elective coronary stent implantation.

OBJECTIVES: With an intracoronary electrocardiogram (IcECG) recording with insulated polymer-coated guidewire without balloon catheter, we sought to examine the association between ST-segment elevation in the IcECG after elective stenting and myocardial injury. BACKGROUND: An IcECG is a sensitive method to detect local myocardial ischemia. Occasionally, persistent ST-segment elevation in the IcECG was recorded after successful coronary intervention. Conventionally IcECG was recorded with a guidewire and over-the-wire system. METHODS: Patients who underwent elective stenting were enrolled (n = 339). The IcECG both at baseline and after procedure were obtained with a guidewire with an insulating coated shaft suitable for IcECG recording. The presence of chest pain after percutaneous coronary intervention was recorded. Cardiac biomarkers were examined 18 h after the procedure. RESULTS: The ST-segment elevation in the IcECG after procedure was recorded in 65 patients, and no change was recorded in 274 patients. Troponin-T, creatine phosphokinase, and creatine kinase MB isoform after the procedure were significantly higher in patients with post-procedural ST-segment elevation in the IcECG than patients without ST-segment elevation. Multivariate analysis demonstrated that ST-segment elevation in the IcECG is an independent predictor of post-procedural myocardial injury. The incidence of ST-segment elevation in the IcECG was significantly higher in patients with post-procedural chest pain than patients without chest pain (p < 0.001). CONCLUSIONS: We demonstrated a facile method to record IcECG with a guidewire with a polymer-coated shaft. The IcECG is a useful method for predicting post-procedural myocardial injuries.

Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol.

In patients routinely treated with metoprolol, influences of CYP2D6 genotype on the response of heart rate to isoproterenol (IP) were studied at its peak and trough concentrations and were compared with those of bisoprolol. In 72 patients treated with metoprolol or bisoprolol, CYP2D6 genotype (ie, CYP2D6*1, *2, *4, *5, *10, and *14) was determined. No patients except one who was heterozygous for CYP2D6*5 carried the null alleles of CYP2D6. The homozygote frequency for CYP2D6*10 was relatively high (19.4%) and these patients had greater peak and trough plasma concentrations of metoprolol than the other patients. Isoproterenol-induced percentage increases in heart rate were 58% and 38% less at the low and high rate of isoproterenol infusion (0.02 and 0.04 microg/kg/min), respectively, in patients homozygous for CYP2D6*10 than in the other patients at the trough, but not at the peak concentrations. In contrast, CYP2D6 genotype did not affect plasma concentrations of bisoprolol and the extent of its beta-adrenergic inhibition. Thus, in patients routinely treated with metoprolol, CYP2D6 genotype significantly affects circadian variations of beta-adrenergic inhibition induced by metoprolol. In contrast, bisoprolol has a relatively constant beta-adrenergic inhibition independent of CYP2D6 genotype.

Ischemia-induced norepinephrine release, but not norepinephrine-derived free radicals, contributes to myocardial ischemia-reperfusion injury.

BACKGROUND: Norepinephrine (NE)-derived free radicals may contribute to myocyte injury after ischemia -reperfusion, so the influence of sympathetic denervation on myocardial ischemia - reperfusion injury was investigated in the present study. METHODS AND RESULTS: Cardiac sympathetic denervation was produced in Wistar rats by a solution of 10% phenol 1 week before ischemia. Atenolol (0.5 mg/kg) was intravenously administered 10 min before the coronary occlusion. The left coronary artery was occluded for 30 min and thereafter reperfused. Cardiac interstitial fluid was collected by a microdialysis probe and free radicals in dialysate were determined by electron paramagnetic resonance (EPR) spin trapping, using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. The ratio of infarct size to the ischemic area at risk (I/R) was decreased in both the phenol and atenolol groups compared with control (28.5+/-11.3, 31.8+/-10.7 vs 50.6+/-14.7%, p<0.05). During the coronary occlusion, concentrations of interstitial NE increased markedly in the control and atenolol groups, but was unchanged in the phenol group. EPR signal intensity (relative value to internal standard) was maximal at 1 h after reperfusion and was similar in the phenol and control groups (0.32+/-0.15 vs 0.45+/-0.19). CONCLUSIONS: Cardiac denervation protected myocyte against ischemia-reperfusion injury through decreasing direct NE toxicity, but not through decreasing NE-derived free radicals.