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.

Unexplained syncope--is screening for carotid sinus hypersensitivity indicated in all patients aged >40 years?

OBJECTIVE: To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15-92 years) referred to two autonomic referral centres during a 10-year period. METHODS: Carotid sinus massage (CSM) was performed both supine and during 60 degree head-up tilt. Beat-to-beat blood pressure, heart rate and a three-lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole > or = 3 s), vasodepressor (systolic blood pressure fall > or = 50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure. RESULTS: CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged < 50 years (n = 65), 2.4% in those aged 50-59 years (n = 82), 9.1% in those aged 60-69 years (n = 77), 20.7% in those aged 70-79 years (n = 92) and reached 40.4% in those > 80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none. CONCLUSIONS: CSH was confirmed in patients > 50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients > 40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them.

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.

Diagnostic accuracy of 64-slice computed tomography for detecting angiographically significant coronary artery stenosis in an unselected consecutive patient population: comparison with conventional invasive angiography

BACKGROUND: Multislice computed tomography (MSCT) is a promising noninvasive method of detecting coronary artery disease (CAD). However, most data have been obtained in selected series of patients. The purpose of the present study was to investigate the accuracy of 64-slice MSCT (64 MSCT) in daily practice, without any patient selection. METHODS AND RESULTS: Using 64-slice MSCT coronary angiography (CTA), 69 consecutive patients, 39 (57%) of whom had previously undergone stent implantation, were evaluated. The mean heart rate during scan was 72 beats/min, scan time 13.6 s and the amount of contrast media 72 mL. The mean time span between invasive coronary angiography (ICAG) and CTA was 6 days. Significant stenosis was defined as a diameter reduction of > 50%. Of 966 segments, 884 (92%) were assessable. Compared with ICAG, the sensitivity of CTA to diagnose significant stenosis was 90%, specificity 94%, positive predictive value (PPV) 89% and negative predictive value (NPV) 95%. With regard to 58 stented lesions, the sensitivity, specificity, PPV and NPV were 93%, 96%, 87% and 98%, respectively. On the patient-based analysis, the sensitivity, specificity, PPV and NPV of CTA to detect CAD were 98%, 86%, 98% and 86%, respectively. Eighty-two (8%) segments were not assessable because of irregular rhythm, calcification or tachycardia. CONCLUSION: Sixty-four-MSCT has a high accuracy for the detection of significant CAD in an unselected patient population and therefore can be considered as a valuable noninvasive technique.

Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology

OBJECTIVES: The goal of the present study was to compare the accuracy of in vivo tissue characterization obtained by intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, known as Virtual Histology (VH), to the in vitro histopathology of coronary atherosclerotic plaques obtained by directional coronary atherectomy. BACKGROUND: Vulnerable plaque leading to acute coronary syndrome (ACS) has been associated with specific plaque composition, and its characterization is an important clinical focus. METHODS: Virtual histology IVUS images were performed before and after a single debulking cut using directional coronary atherectomy. Debulking region of in vivo histology image was predicted by comparing pre- and post-debulking VH images. Analysis of VH images with the corresponding tissue cross section was performed. RESULTS: Fifteen stable angina pectoris (AP) and 15 ACS patients were enrolled. The results of IVUS RF data analysis correlated well with histopathologic examination (predictive accuracy from all patients data: 87.1% for fibrous, 87.1% for fibro-fatty, 88.3% for necrotic core, and 96.5% for dense calcium regions, respectively). In addition, the frequency of necrotic core was significantly higher in the ACS group than in the stable AP group (in vitro histopathology: 22.6% vs. 12.6%, p = 0.02; in vivo virtual histology: 24.5% vs. 10.4%, p = 0.002). CONCLUSIONS: Correlation of in vivo IVUS RF data analysis with histopathology shows a high accuracy. In vivo IVUS RF data analysis is a useful modality for the classification of different types of coronary components, and may play an important role in the detection of vulnerable plaque.

Coronary plaque composition of culprit/target lesions according to the clinical presentation: a virtual histology intravascular ultrasound analysis

AIMS: To evaluate the plaque composition obtained by virtual histology (VH) IVUS according to the clinical presentation and to compare those data to previously published histopathology data. METHODS AND RESULTS: VH was performed on 95 de novo significant lesions (>75% stenosis) in 85 patients [28 acute coronary syndrome (ACS) patients, 30 lesions; 57 stable angina pectoris (SAP) patients, 65 lesions]. There were a higher prevalence of positive remodelling (47 vs. 22%, P=0.013), thrombus (20 vs. 1.5%, P=0.0037), and echo-lucent area (23.3 vs. 7.7%, P=0.047) in ACS patients. At the minimal lumen site, fibrous plaque area was significantly larger in ACS lesions than in SAP lesions (66.0+/-10.7 vs. 61.4+/-8.9%, P=0.034), whereas necrotic core and dense calcium plaque area were smaller in ACS lesions (Necrotic core: 6.8+/-6.0 vs. 11.0+/-8.3%, P=0.02; Dense calcium: 2.6+/-3.0 vs. 4.9+/-5.8%, P=0.03). No differences in rate of thin cap fibroatheroma, thick fibrotheroma, or for the presence of multiple necrotic core layers were observed between both groups. CONCLUSION: Plaque composition obtained by VH-IVUS shows less necrotic core and more fibrous tissue in ACS compared to SAP lesions, which is in contradiction with previously published histopathologic data.

Self-Reported Memory Symptoms with Coronary Artery Disease: A Prospective of CABG Patients and Nonsurgical Controls

Background. Subjective memory complaints are common after coronary artery bypass grafting (CABG), but previous studies have concluded that such symptoms are more closely associated with depressed mood than objective cognitive dysfunction. We compared the incidence of self-reported memory symptoms at 3 and 12 months after CABG with that of a control group of patients with comparable risk factors for coronary artery disease but without surgery. Methods. Patients undergoing CABG (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) were followed prospectively at 3 and 12 months. At each follow-up time, participants were asked about changes since the previous evaluation in areas of memory, calculations, reading, and personality. A Functional Status Questionnaire (FSQ) and self-report measure of symptoms of depression (CES-D) were also completed. Results. The frequency of self-reported changes in memory, personality, and reading at 3 months was significantly higher among CABG patients than among nonsurgical controls. By contrast, there were no differences in the frequency of self-reported symptoms relating to calculations or overall rating of functional status. After adjusting for a measure of depression (CES-D rating score), the risk for self-reported memory changes remained nearly 5 times higher among the CABG patients than control subjects. The relative risk of developing new self-reported memory symptoms between 3 and 12 months was 2.5 times higher among CABG patients than among nonsurgical controls (CI 1.24 – 5.02), and the overall prevalence of memory symptoms at 12 months was also higher among CABG patients (39%) than controls (14%). Conclusions. The frequency of self-reported memory symptoms 3 and 12 months after baseline is significantly higher among CABG patients than control patients with comparable risk factors for coronary and cerebrovascular disease. These differences could not be accounted for by symptoms of depression. The self-reported cognitive symptoms appear to be relatively specific for memory, and may reflect aspects of memory functioning that are not captured by traditional measures of new verbal learning and memory. The etiology of these self-reported memory symptoms remains unclear, but our findings as well as those of others, may implicate factors other than cardiopulmonary bypass itself.

A meta-analysis of 16 randomized trials of sirolimus-eluting stents versus paclitaxel-eluting stents in patients with coronary artery disease

OBJECTIVES: Our purpose was to make a synthesis of the available evidence on the relative efficacy and safety of 2 drug-eluting stents (DES)--sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES)--in patients with coronary artery disease. BACKGROUND: It is not known whether there are differences in late outcomes between the 2 most commonly used DES: SES and PES. METHODS: Sixteen randomized trials of SES versus PES with a total number of 8,695 patients were included in this meta-analysis. A full set of individual outcome data from 5,562 patients was also available. Mean follow-up period ranged from 9 to 37 months. The primary efficacy end point was the need for reintervention (target lesion revascularization). The primary safety end point was stent thrombosis. Secondary end points were death and recurrent myocardial infarction (MI). RESULTS: No significant heterogeneity was found across trials. Compared with PES, SES significantly reduced the risk of reintervention (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 to 0.87, p < 0.001) and stent thrombosis (HR 0.66; 95% CI 0.46 to 0.94, p = 0.02) without significantly impacting on the risk of death (HR 0.92; 95% CI 0.74 to 1.13, p = 0.43) or MI (HR 0.84; 95% CI 0.69 to 1.03, p = 0.10). CONCLUSIONS: Sirolimus-eluting stents are superior to PES in terms of a significant reduction of the risk of reintervention and stent thrombosis. The risk of death was not significantly different between the 2 DES, but there was a trend toward a higher risk of MI with PES, especially after the first year from the procedure.

Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients

ATP-binding-cassette-transporter-A1 (ABCA1) plays a pivotal role in intracellular cholesterol removal, exerting a protective effect against atherosclerosis. ABCA1 gene severe mutations underlie Tangier disease, a rare Mendelian disorder that can lead to premature coronary artery disease (CAD), with age of CAD onset being two decades earlier in mutant homozygotes and one decade earlier in heterozygotes than in mutation non-carriers. It is unknown whether common polymorphisms in ABCA1 could influence age of symptom onset of CAD in the general population. We examined common promoter and non-synonymous coding polymorphisms in relation to age of symptom onset in a group of CAD patients (n = 1164), and also carried out in vitro assays to test effects of the promoter variations on ABCA1 promoter transcriptional activity and effects of the coding variations on ABCA1 function in mediating cellular cholesterol efflux. Age of symptom onset was found to be associated with the promoter - 407G > C polymorphism, being 2.82 years higher in C allele homozygotes than in G allele homozygotes and intermediate in heterozygotes (61.54, 59.79 and 58.72 years, respectively; P = 0.002). In agreement, patients carrying ABCA1 haplotypes containing the -407C allele had higher age of symptom onset. Patients of the G/G or G/C genotype of the -407G > C polymorphism had significant coronary artery stenosis (>75%) at a younger age than those of the C/C genotype (P = 0.003). Reporter gene assays showed that ABCA1 haplotypes bearing the -407C allele had higher promoter activity than haplotypes with the -407G allele. Functional analyses of the coding polymorphisms showed an effect of the V825I substitution on ABCA1 function, with the 825I variant having higher activity in mediating cholesterol efflux than the wild-type (825V). A trend towards higher symptom onset age in 825I allele carriers was observed. The data indicate an influence of common ABCA1 functional polymorphisms on age of symptom onset in CAD patients.

Uterine fibroid embolization: the utility of aortography in detecting ovarian artery collateral supply

PURPOSE: To retrospectively determine the sensitivity of ovarian artery (OA) visualization at aortography performed after uterine fibroid embolization (UFE) and, using OA arteriography as the reference standard, compare the extent of arterial flow to the uterus at aortography with selective ovarian arteriography, to establish the utility of aortography and ovarian arteriography in the routine practice of UFE. MATERIALS AND METHODS: This study received institutional review board approval with waiver of informed consent and was HIPAA compliant. Retrospective review of 1129 consecutive UFE patients (1072 with aortograms, 57 excluded; mean age, 44 years; range, 21-60 years) was performed to identify all visible OAs. Visible OAs were independently graded by two interventional radiologists according to extent of pelvic arterial flow. If selective arteriography was performed, a second grade was assigned based on assessment of the selective study. Descriptive and summary statistics were used for assessment by the senior observer, and interobserver variability was determined. RESULTS: Of 1072 UFE patients, 184 (17.2%) had at least one visible OA. Ten (0.8%) patients were identified at aortography with collateral OA supply to more than 10% of the uterus. In total, 251 OAs were visualized, and 157 of these were further evaluated with selective study. Sixty-two (5.8%) patients were identified at selective arteriography as having collateral OA supply. The sensitivity of aortography was approximately 18%. Interobserver concordance was high (kappa values of 0.81 and 0.90 for aortography and selective study, respectively), but not perfect. CONCLUSION: Aortography rarely helps identify patients with substantial residual OA supply to the uterus and is a poor predictor of the extent of that supply, and thus may be of limited utility in routine UFE.

Cystic adventitial disease of the popliteal artery: an argument for the developmental theory

Cystic adventitial disease is a rare non-atheromatous cause of popliteal artery disease. We report a case of a 54-year-old patient with claudication of the right calf caused by cystic adventitial disease. Intra-operatively, a communication between the adventitia and the knee joint was identified. Connections between the adventitial cyst and the nearby joint have been reported in the literature that support the developmental theory. This theory suggests that cystic adventitial disease is a developmental manifestation of mucin-secreting cells derived from the mesenchyme of the adjacent joint. This case is the first, to our knowledge, in which a communication between joint and adventitia has been clearly documented by operative findings.