Absence of histamine-induced nitric oxide release in the human radial artery: implications for vasospasm of coronary artery bypass vessels

Radial artery (RA) bypass grafts can develop severe vasospasm. As histamine is known to induce vasospasm, its effect on RA was assessed compared with the classic bypass vessels internal mammary artery (MA) and saphenous vein (SV). The vessels were examined in organ chambers for isometric tension recording. Histamine induced contractions on baseline; the sensitivity was higher in RA and SV than MA. After precontraction with norepinephrine, histamine did not evoke relaxations of RA but induced relaxations of MA and less of SV at lower concentrations; it induced contractions at higher concentrations, reaching similar levels in all three vessels. Indomethacin did not affect the response of MA and RA but potentiated relaxations and reduced contractions of SV. Endothelium removal, N(omega)-nitro-L-arginine methyl ester (L-NAME), or the H2-receptor blocker cimetidine did not affect the response of RA, but inhibited relaxations and enhanced contractions in MA and inhibited relaxations in SV; in the latter, only L-NAME enhanced contractions. Real-time PCR detected much lower expression of endothelial H2-receptor in RA than MA or SV. Western blots revealed similar endothelial nitric oxide (NO) synthase expression in all three vessels. Relaxations to acetylcholine were identical in RA and MA. Thus histamine releases NO by activating the endothelial H2-receptor, the expression of which is much lower in RA than MA or SV. H2-receptor activation also releases prostaglandins in SV, partially antagonizing NO. The lack of histamine-induced NO production represents a possible mechanism of RA vasospasm.

Percutaneous coronary interventions in Europe: prevalence, numerical estimates, and projections based on data up to 2004

AIMS: A registry mandated by the European Society of Cardiology collects data on trends in interventional cardiology within Europe. Special interest focuses on relative increases and ratios in new techniques and their distributions across Europe. We report the data through 2004 and give an overview of the development of coronary interventions since the first data collection in 1992. METHODS AND RESULTS: Questionnaires were distributed yearly to delegates of all national societies of cardiology represented in the European Society of Cardiology. The goal was to collect the case numbers of all local institutions and operators. The overall numbers of coronary angiographies increased from 1992 to 2004 from 684 000 to 2 238 000 (from 1250 to 3930 per million inhabitants). The respective numbers for percutaneous coronary interventions (PCIs) and coronary stenting procedures increased from 184 000 to 885 000 (from 335 to 1550) and from 3000 to 770 000 (from 5 to 1350), respectively. Germany was the most active country with 712 000 angiographies (8600), 249 000 angioplasties (3000), and 200 000 stenting procedures (2400) in 2004. The indication has shifted towards acute coronary syndromes, as demonstrated by rising rates of interventions for acute myocardial infarction over the last decade. The procedures are more readily performed and perceived safer, as shown by increasing rate of "ad hoc" PCIs and decreasing need for emergency coronary artery bypass grafting (CABG). In 2004, the use of drug-eluting stents continued to rise. However, an enormous variability is reported with the highest rate in Switzerland (70%). If the rate of progression remains constant until 2010 the projected number of coronary angiographies will be over three million, and the number of PCIs about 1.5 million with a stenting rate of almost 100%. CONCLUSION: Interventional cardiology in Europe is ever expanding. New coronary revascularization procedures, alternative or complementary to balloon angioplasty, have come and gone. Only stenting has stood the test of time and matured to the default technique. Facilitated access to PCI, more complete and earlier detection of coronary artery disease promise continued growth of the procedure despite the uncontested success of prevention.

Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial

CONTEXT: Compared with bare metal stents, sirolimus-eluting and paclitaxel-eluting stents have been shown to markedly improve angiographic and clinical outcomes after percutaneous coronary revascularization, but their performance in the treatment of de novo coronary lesions has not been compared in a prospective multicenter study. OBJECTIVE: To compare the safety and efficacy of sirolimus-eluting vs paclitaxel-eluting coronary stents. DESIGN: Prospective, randomized comparative trial (the REALITY trial) conducted between August 2003 and February 2004, with angiographic follow-up at 8 months and clinical follow-up at 12 months. SETTING: Ninety hospitals in Europe, Latin America, and Asia. PATIENTS: A total of 1386 patients (mean age, 62.6 years; 73.1% men; 28.0% with diabetes) with angina pectoris and 1 or 2 de novo lesions (2.25-3.00 mm in diameter) in native coronary arteries. INTERVENTION: Patients were randomly assigned in a 1:1 ratio to receive a sirolimus-eluting stent (n = 701) or a paclitaxel-eluting stent (n = 685). MAIN OUTCOME MEASURES: The primary end point was in-lesion binary restenosis (presence of a more than 50% luminal-diameter stenosis) at 8 months. Secondary end points included 1-year rates of target lesion and vessel revascularization and a composite end point of cardiac death, Q-wave or non-Q-wave myocardial infarction, coronary artery bypass graft surgery, or repeat target lesion revascularization. RESULTS: In-lesion binary restenosis at 8 months occurred in 86 patients (9.6%) with a sirolimus-eluting stent vs 95 (11.1%) with a paclitaxel-eluting stent (relative risk [RR], 0.84; 95% confidence interval [CI], 0.61-1.17; P = .31). For sirolimus- vs paclitaxel-eluting stents, respectively, the mean (SD) in-stent late loss was 0.09 (0.43) mm vs 0.31 (0.44) mm (difference, -0.22 mm; 95% CI, -0.26 to -0.18 mm; P<.001), mean (SD) in-stent diameter stenosis was 23.1% (16.6%) vs 26.7% (15.8%) (difference, -3.60%; 95% CI, -5.12% to -2.08%; P<.001), and the number of major adverse cardiac events at 1 year was 73 (10.7%) vs 76 (11.4%) (RR, 0.94; 95% CI, 0.69-1.27; P = .73). CONCLUSION: In this trial comparing sirolimus- and paclitaxel-eluting coronary stents, there were no differences in the rates of binary restenosis or major adverse cardiac events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00235092.

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

BACKGROUND: Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. METHODS: Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13,100 men aged 40-70 and 114,443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. RESULTS: A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. CONCLUSIONS: The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle changes.

Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial

CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known. OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI. DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin. MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up. RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.

Does the beta-blocker nebivolol increase coronary flow reserve?

INTRODUCTION: Nebivolol, a highly selective beta1-adrenergic receptor-blocker, increases basal and stimulated endothelial nitric oxide (NO)-release. It is unknown, whether coronary perfusion is improved by the increase in NO availability. Therefore, we sought to evaluate the effect of nebivolol on coronary flow reserve (CFR) and collateral flow. METHODS: Doppler-flow wire derived coronary flow velocity measurements were obtained in ten controls and eight patients with coronary artery disease (CAD) at rest and after intracoronary nebivolol. CFR was defined as maximal flow during adenosine-induced hyperemia divided by resting flow. In the CAD group, collateral flow was determined after dilatation of a flow-limiting coronary stenosis. Collateral flow index (CFI) was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: CFR at rest was 3.0+/-0.6 in controls and 2.1+/-0.4 in CAD patients. After intracoronary doses of 0.1, 0.25, and 0.5 mg nebivolol, CFR increased to 3.4+/-0.7, 3.9+/-0.9, and 4.0+/-0.1 (p<0.01) in controls, and to 2.3+/-0.7, 2.6+/-0.9, and 2.6+/-0.5 (p<0.05) in CAD patients. CFI decreased significantly with intracoronary nebivolol and correlated to changes in heart rate (r=0.75, p<0.001) and rate-pressure product (r=0.59, p=0.001). DISCUSSION: Intracoronary nebivolol is associated with a significant increase in CFR due to reduction in resting flow (controls), or due to an increase in maximal coronary flow (CAD patients). CFI decreased with nebivolol parallel to the reduction in myocardial oxygen consumption.

Local vascular dysfunction after coronary paclitaxel-eluting stent implantation

BACKGROUND: Paclitaxel-eluting stents (PES) have been shown to reduce the rate of restenosis and the need for repeated revascularization procedures compared with bare metal stents. However, long-term effects of paclitaxel on vascular function are unknown. The purpose of the present study was to assess coronary vasomotor response to exercise after paclitaxel-eluting stent implantation. METHODS: Coronary vasomotion was evaluated by biplane quantitative coronary angiography at rest and during supine bicycle exercise in 27 patients with coronary artery disease. Twelve patients were treated with a bare metal stent (controls), and fifteen patients with a paclitaxel-eluting stent. All patients were restudied 6+/-2 (range 2-12) months after stent implantation. Minimal luminal diameter, stent diameter, proximal, distal and a reference vessel diameter were determined. RESULTS: Reference vessels showed exercise-induced vasodilation in both groups (+20+/-5% controls; +26+/-3% PES group). Vasomotion within the stented vessel segments was abolished. In the controls, the adjacent segments proximal and distal to the stent showed exercise-induced vasodilation (+17+/-3% and +24+/-4%). In contrast, there was exercise-induced vasoconstriction of the proximal and distal vessel segments adjacent to the paclitaxel-eluting stent (-13+/-6% and -18+/-4%; p<0.005). After sublingual nitroglycerin, the proximal and distal vessel segments dilated in both groups. Exercise-induced vasoconstriction adjacent to paclitaxel-eluting stent correlated inversely with the time interval after stent implantation. CONCLUSIONS: Paclitaxel-eluting stent implantation is associated with exercise-induced vasoconstriction in the persistent region suggesting endothelial dysfunction as the underlying mechanism. Improvement of vascular function occurs over time, indicating delayed vascular healing.

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.

Coronary artery stent geometry and in-stent contrast attenuation with 64-slice computed tomography

We aimed at assessing stent geometry and in-stent contrast attenuation with 64-slice CT in patients with various coronary stents. Twenty-nine patients (mean age 60 +/- 11 years; 24 men) with 50 stents underwent CT within 2 weeks after stent placement. Mean in-stent luminal diameter and reference vessel diameter proximal and distal to the stent were assessed with CT, and compared to quantitative coronary angiography (QCA). Stent length was also compared to the manufacturer's values. Images were reconstructed using a medium-smooth (B30f) and sharp (B46f) kernel. All 50 stents could be visualized with CT. Mean in-stent luminal diameter was systematically underestimated with CT compared to QCA (1.60 +/- 0.39 mm versus 2.49 +/- 0.45 mm; P < 0.0001), resulting in a modest correlation of QCA versus CT (r = 0.49; P < 0.0001). Stent length as given by the manufacturer was 18.2 +/- 6.2 mm, correlating well with CT (18.5 +/- 5.7 mm; r = 0.95; P < 0.0001) and QCA (17.4 +/- 5.6 mm; r = 0.87; P < 0.0001). Proximal and distal reference vessel diameters were similar with CT and QCA (P = 0.06 and P = 0.03). B46f kernel images showed higher image noise (P < 0.05) and lower in-stent CT attenuation values (P < 0.001) than images reconstructed with the B30f kernel. 64-slice CT allows measurement of coronary artery in-stent density, and significantly underestimates the true in-stent diameter compared to QCA.

Clinical relevance of coronary angiography at the time of percutaneous closure of a patent foramen ovale

BACKGROUND: The value of incidental coronary angiography during percutaneous shunt closure to screen for asymptomatic coronary artery disease (CAD) is unknown. METHODS: On the occasion of percutaneous closure of patent foramen ovale (PFO), incidental coronary angiography routinely offered to men >40 and women >50 years, or younger patients with particular risk patterns, was performed in 575 patients (64% men, mean age 55 +/- 10 years, mean 1.5 +/- 1.1 cardiovascular risk factors) without overt history, signs, or symptoms of CAD. RESULTS: CAD was found in 164 patients (29%); 53 (9%) had >or=50% diameter stenoses. Thirty patients (5%) had one-vessel, 13 (2%) two-vessel, and 10 (2%) three-vessel disease. Patients with CAD (n = 164) were older (60 +/- 9 vs. 53 +/- 10 years; P < 0.0001), more frequently male (76% vs. 59%; P = 0.0002), and had a higher body mass index (26.5 +/- 4.0 vs. 25.4 +/- 4.6; P = 0.006) and more cardiovascular risk factors (2.0 +/- 1.1 vs. 1.2 +/- 1.0; P < 0.0001). There were six procedural complications (1%). Two were unequivocally related to coronary angiography: one minor stroke (diplopia), and one iatrogenic dissection of the right coronary ostium requiring stenting. Furthermore, four arteriovenous fistulae at the puncture site requiring elective surgical closure were possibly related to coronary angiography. Forty-five patients (8% of total) underwent percutaneous (n = 43) or surgical (n = 2) revascularization. CONCLUSIONS: In selected asymptomatic patients referred for percutaneous PFO closure, incidental coronary angiography discloses a rather high prevalence of clinically unsuspected CAD. These findings are relevant not only for timely revascularization but also for maintenance of long-term antiplatelet therapy beyond the few months recommended after PFO closure.

Is right coronary artery hypoplasia and sudden death an underdiagnosed association?

Determining whether hypoplasia of a coronary artery has caused or contributed to death is often complicated by an absence of histologic evidence of myocardial ischemia in the area of the heart supplied by the affected artery and also by the lack of data for assessing coronary artery size at autopsy. A 45-year-old woman is reported who collapsed and died and who was found at autopsy to have a dominant, small-caliber, right coronary artery, with acute and chronic ischemic changes in the posterior interventricular septum supplied by the diminutive vessel. This case provides evidence that small-caliber coronary arteries may be associated with a lethal outcome. Given the difficulties that may occur in determining whether there is a causal link between small coronary artery caliber and death, it is possible that this may be an underdiagnosed cause of sudden cardiac death, rather than a coincidental finding of minimal significance.

Acute pulmonary embolectomy three days following a coronary artery bypass graft procedure

Pulmonary embolism is very rarely reported early after cardiac surgery, most probably due to full heparinisation during cardiopulmonary bypass. We report a 66-year-old man without thromboembolic history who presented three days after a coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic instability. A CT scan confirmed paracentral bilateral pulmonary embolism requiring an urgent and successful embolectomy. Review of the literature confirms that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass patients. The possibility of pulmonary embolism must be taken into consideration in post-cardiopulmonary bypass patients with acute onset of chest pain and respiratory insufficiency.