Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of 'bridging' antiplatelet therapy with tirofiban during temporary withdrawal of clopidogrel.

BACKGROUND: Patients with a recently implanted coronary drug-eluting stent (DES) who need urgent surgery are at increased risk of surgical bleeding unless clopidogrel is discontinued beforehand, but clopidogrel discontinuation has been associated with a high rate of adverse events due to stent thrombosis. This pilot study tested the hypothesis that the i.v. perioperative administration of the short-acting antiplatelet agent tirofiban allows the safe withdrawal of clopidogrel without increasing the rate of surgical bleeding. METHODS: Phase II study with a Simon two-stage design. RESULTS: Thirty patients with a recently implanted DES [median (range) 4 (1-12) months] and high-risk characteristics for stent thrombosis underwent urgent major surgery or eye surgery. Clopidogrel was to be withdrawn 5 days before surgery, and tirofiban started 24 h later, continued until 4 h before surgery, and resumed 2 h after surgery until oral clopidogrel was resumed. The use of aspirin was decided by the surgeon. There were no cases of death, myocardial infarction, stent thrombosis, or surgical re-exploration due to bleeding during the index admission, with a risk estimate of 0-11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial infarction (TIMI) major and one of TIMI minor bleeding in the postoperative phase; another four patients were transfused without meeting the TIMI criteria for major or minor bleeding. CONCLUSIONS: In patients with a recently implanted DES and high-risk characteristics for stent thrombosis needing urgent surgery, a 'bridging strategy' using i.v. tirofiban may allow temporary withdrawal of oral clopidogrel without increasing the risk of bleeding.

Cryoballoon ablation of atrial fibrillation is effectively feasible without previous imaging of pulmonary vein anatomy: insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. METHODS: Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. RESULTS: Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p < 0.001). The procedure, fluoroscopy, and left atrial dwell times were significantly shorter in the no imaging cohort (p < 0.001). The rates of complications were significantly greater in the imaging group compared to the no imaging group (6.9% vs. 2.7%; p = 0.003); this difference was attributed to differences in transient diaphragmatic paralysis. The 12-month freedom from AF was 76.2% in the imaging group and 80.0% in the no imaging group (p = 0.390). CONCLUSIONS: In our analysis, PVI-C was effective regardless of the availability of imaging data on PV anatomy.

Psoriasis and the risk of acute coronary syndrome in the elderly.

BACKGROUND: Psoriasis has been associated with a higher prevalence of cardiovascular disease risk factors. However, there is inadequate quantification on the association between psoriasis and acute coronary syndrome (ACS), particularly in the elderly. Therefore, the aim of the present study was to assess the risk of ACS according to history of psoriasis in subjects aged 75 years and older. METHODS: We carried out a case control study based on 1455 cases and 1108 controls. Cases were all the patients admitted in the randomized Elderly ACS 2 trial. Controls were selected from subjects aged ≥75 years included in the Prevalence of Actinic Keratoses in the Italian Population Study (PraKtis), based on a representative sample of the general Italian population. Odds ratios (OR) of ACS according to history of psoriasis were obtained using a multiple logistic regression model including terms for age, sex and smoking. RESULTS: The prevalence of psoriasis was lower among cases (12/1455, 0.8%) than among controls (18/1108, 1.6%). The multivariate OR of ACS according to history of psoriasis was 0.51 (95% confidence interval: 0.23-1.09). CONCLUSIONS: Our data does not support an association between psoriasis and risk of ACS in the elderly.

Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes.

BACKGROUND: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients. METHODS: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score >14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1month, compared to TSMs. RESULTS: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1month). CONCLUSIONS: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype.

[From the SIN Mailing List: the use of hemodialysis after radiocontrast media administration in patients with chronic renal failure]. / Dalla Mailing-List soci SIN (ML-SIN). Il ruolo della dialisi nella nefropatia da mezzo di contrasto: dubbi e certezze.

Over the last few years there has been a progressive increase in percutaneous endovascular procedures in patients with chronic renal disease, due to the high incidence of vascular disease, particularly coronary artery disease, in this population. The use of contrast medium may further worsen renal function in such patients, in some cases even accelerating the progression towards end-stage renal failure, and increase patients morbidity and mortality. In this review we discuss the role of dialysis in preventing contrast-induced nephropathy and indications to its use in patients already on dialysis treatment undergoing diagnostic or therapeutic procedures with contrast medium injection.

Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease.

Leukotriene C4 is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4 release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II). To assess leukotriene C4 generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 microM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4 by radioimmunoassay. Patients in group I had a significantly lower release of leukotriene C4 from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 +/- 0.69 versus 5.92 +/- 0.54 ng/ml, p less than 0.025), whereas patients in group II had a similar release of leukotriene C4 by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 +/- 0.72 versus 6.4 +/- 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p less than 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4 released from neutrophils separated from coronary sinus blood as compared with leukotriene C4 produced by neutrophils separated from aortic blood. These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4 after stimulation by calcium ionophore A 23187.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance of exercise-induced silent myocardial ischemia in patients with coronary artery disease.

Exercise-induced silent myocardial ischemia is a frequent feature in patients with coronary artery disease. The purpose of this study was to compare the clinical and angiographic characteristics of 269 patients who complained of chest pain during an exercise test (group I) with those of 204 who developed exercise-induced silent myocardial ischemia (group II). Group I patients more frequently had anginal symptoms of class III and IV of the Canadian Cardiovascular Society than did group II patients, who had milder symptoms (p less than 0.001). The only angiographic difference observed between the two groups was a slightly but significantly higher left ventricular end-diastolic pressure in group II patients (p less than 0.05), who also showed a longer exercise duration (p less than 0.01) with a higher heart rate-systolic pressure product (p less than 0.01) and more pronounced ST segment depression at peak exercise (p less than 0.001). Moreover, ventricular ectopic beats during exercise were more frequently observed in group II patients (p less than 0.05). Coronary bypass surgery was performed in 45% of patients of group I and in 24% of patients of group II (p less than 0.05). Survival curves of medically treated patients did not show any statistically significant difference between the two groups. Thus, although patients with a defective anginal warning system may have more pronounced signs of myocardial ischemia and a greater incidence of ventricular arrhythmias during exercise, their long-term prognosis is not different from that of patients who are stopped by angina from the activity that is inducing myocardial ischemia.

Clinical and angiographic correlates of leukocyte activation in unstable angina.

OBJECTIVES: This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated. BACKGROUND: Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition. METHODS: Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers. RESULTS: In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood. CONCLUSION: These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

Significance of hyperventilation-induced ST segment depression in patients with coronary artery disease.

To investigate the significance of hyperventilation-induced ST segment depression, 329 consecutive patients with angina and documented coronary artery disease who underwent hyperventilation and exercise tests during pharmacologic washout were studied. The hyperventilation test induced ST segment depression in 79 patients. In 36 of these 79 patients, the electrocardiographic changes occurred early during overbreathing (Group I), whereas in 26 they occurred late during recovery (Group II). Seventeen patients developed ST segment depression both during over-breathing and during recovery (Group III). Group I patients had a higher frequency of history of angina during exercise, multivessel disease and lower tolerance to exercise as compared with patients in Group II. In Group I, the rate-pressure product at the time to onset of ST depression during overbreathing was similar to that during exercise (152 +/- 24 versus 148 +/- 42; p = NS), whereas in Group II the rate-pressure product at the time to onset of ST depression during recovery was comparable with that under control conditions (104 +/- 30 versus 98 +/- 27; p = NS) and far less than that required to produce ischemia during exercise (104 +/- 30 versus 201 +/- 56; p less than 0.0011). In nine Group III patients, the acute administration of propranolol prevented the early hyperventilation-induced ST segment depression, whereas nifedipine abolished the delayed hyperventilation-induced ST segment depression. These findings suggest that early hyperventilation-induced ST segment depression is due to increased oxygen demand in patients with poor coronary reserve and may be prevented by beta-adrenergic blockers, which are useful for lowering oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

New trends in coronary artery disease: the role of granulocyte activation.

Circulating granulocytes play an important role in microvascular perfusion and organ pathology. Oxygen radicals released by aggregated and activated neutrophils may exacerbate the tissue damage caused by ischemia. We studied neutrophil aggregation and oxygen metabolites release in 16 patients suffering from coronary artery disease and in 6 control subjects in aorta and coronary sinus blood samples. The neutrophil aggregation (P less than 0.01) and oxidase activity (P less than 0.01) are higher in coronary sinus than aorta samples only in the patients with respect to controls. While the superoxide generation is decreased in coronary sinus (P less than 0.05). Our aggregation assay supported the potential role of granulocytes in neutrophil-endothelial interactions and tissue damage, and our results about oxidase activity and superoxide release suggested the potential role for neutrophil-derived oxygen radicals in the pathogenesis of vascular injury in vivo.

Role of granulocytes in endothelial injury in coronary heart disease in humans.

Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. A positive correlation was also found between leukocyte count and severity of coronary artery disease. Rabbit derived antiserum dependent-reduction of circulating PMNs in the dog or using monoclonal antibody anti-CD11b/CD18 of PMNs resulted in smaller myocardial infarcts. Granulocytes can release a variety of mediators tissue injury and synergize with these different mediators and other cells resulting in amplification of neutrophil stimulation and rising to additional products with enhanced endothelial injury. This paper reviews "in vivo" studies that have been instrumental in demonstrating this role of granulocytes as a mediator of myocardial ischemia. Experience in humans shows the modification of PMNs function in angina and during myocardial ischemia, and data from our group demonstrated that their aggregability is increased in the coronary sinus of patients with angiographically documented coronary disease. Upon re-perfusion PMNs accumulate and produce an inflammatory response resulting in endothelial injury. Free radicals formed during ischemia or re-perfusion produce deleterious effects on cell membranes, endothelial cell and myocardium. On the other hand the PMNs activation occurring during coronary angioplasty (PTCA) by the release of proteolytic enzymes and the generation of oxygen-free radicals, may aggravate the endothelial damage induced by PTCA and further stimulate platelets having potential implications in subsequent development of restenosis. An other aspect of PMNs function is related to leukotriene C4 release; the vasoconstrictor effect of this leukotriene on coronary arteries is synergistic with that induced by platelet-released thromboxane A2, as well as the decrease in coronary flow produced by the combination of both substances is greater than the sum of changes caused by the two eicosanoids separately administered. The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in pathophysiology of myocardial injury due to a regional ischemia and reperfusion is an area of intense investigation. Experimental and clinical studies to elucidate these events should not only provide insights into acute and chronic pathologic tissue damage, but may also lead to the identification of important new targets of pharmacologic intervention.

Plasma levels of interleukin 2, 6, 10 and phenotypic characterization of circulating T lymphocytes in ischemic heart disease.

The purpose of this study was to assess lymphocyte receptors expression in patients with ischemic heart diseases, as well as to measure the plasma levels of interleukin (IL) 2, 6 and 10. T Lymphocytes are found in large numbers in human atherosclerotic plaques, indicating that immune and inflammatory mechanisms are important factors in the pathogenesis of atherosclerosis. Recent data have also implicated T lymphocytes in the pathogenetic mechanism of unstable angina and ischemic heart disease. Three groups of patients were studied: 42 with an acute ischemic syndrome (AIS), 36 with stable angina (SA) and 39 healthy controls. To characterize lymphocyte phenotype, flow cytometry was performed in whole-blood samples. IL-2, IL-6 and IL-10 were measured using the ELISA method. Double fluorescence evaluation showed an increase in CD8+/CD11b+ cells (cytotoxic T lymphocytes) and in CD11b+/CD16+CD56+ cells (NK lymphocytes) in the AIS group and in SA group as compared to the control group (P < 0.05 and P < 0.001, respectively). IL-2 was increased in the AIS and SA groups compared to the control group (AIS 4.5 +/- 0.5 pg/ml; SA 6.3 +/- 0.6 pg/ml; controls 2.4 +/- 0.8 pg/ml, P < 0.05), whereas IL-6 was higher in the AIS group than in the other two groups (AIS 10.8 +/- 1.8 pg/ml; SA 1.8 +/- 0.8 pg/ml; controls 1.2 +/- 0.6 pg/ml, P < 0.0001). These data show that patients with ischemic heart disease have an increase in circulating cytotoxic T lymphocytes and in IL-2 plasma levels, irrespective of their clinical presentation, compared to normal control subjects, whereas IL-6 is elevated only in patients with AIS.

Granulocyte function in coronary artery disease.

Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty.

Effects of atrial pacing and dipyridamole administration on coronary hemodynamics of collateralized myocardial regions in stable angina pectoris.

Great cardiac vein blood flow by thermodilution and great cardiac vein oxygen saturation were measured in 14 patients with stable exertional angina and an angiographic pattern of complete occlusion of the proximal left anterior descending artery retrogradely filled by collateral vessels supplying still viable myocardium. Measurements were obtained under control conditions, at peak atrial pacing and after dipyridamole administration (0.56 mg/kg intravenously over 4 minutes). Both stress tests induced ischemic electrocardiographic changes in all patients, but dipyridamole administration resulted in greater ST-segment depression in 11 patients (1.6 +/- 0.5 vs 2.4 +/- 1.6 mm, p less than 0.05) and transient ST-segment elevation in 3 patients. Dipyridamole provoked ischemia at a lower value of rate-pressure product (145.3 +/- 30.6 vs 202.9 +/- 36.6 beats/min . mm Hg . 10(-2), p less than 0.0005) and anterior region myocardial oxygen consumption (9.32 +/- 4.76 vs 11.39 +/- 3.91 ml/min, p less than 0.05), despite a greater increase in great cardiac vein flow (139.4 +/- 45 vs 93 +/- 27.4 ml/min, p less than 0.0025) and a greater decrease in the calculated index of anterior region coronary resistance (0.87 +/- 0.27 vs 1.46 +/- 0.43 mm Hg/ml/min, p less than 0.0005). Moreover, great cardiac vein oxygen saturation increased more significantly during dipyridamole-induced ischemia than at peak pacing (63 +/- 12 vs 35 +/- 8%, p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris.

Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Ability of calcium-entry blockade by felodipine to disclose different pathogenetic mechanisms behind hyperventilation-induced myocardial ischemia in men.

To verify that myocardial ischemia occurring during either the overbreathing or recovery phase of the hyperventilation test is based on different pathogenetic mechanisms, 2 consecutive series of patients, selected on the basis of their response to a run-in hyperventilation test, were studied. Group I comprised 15 patients who developed ST-segment depression early during overbreathing, whereas group II consisted of 12 patients showing ST-segment depression late during the recovery phase. A single oral dose of felodipine 10 mg or of placebo was administered on 2 consecutive days according to a randomized, double-blind, crossover design, and the hyperventilation test was repeated, on both days of the study, 3 to 5 hours after drug intake. In group I, ST-segment depression occurred after placebo in all patients during overbreathing, with an increase in rate pressure product (from 112 +/- 31 at baseline to 168 +/- 55 mm Hg x beats/min/100 at the onset of ST-segment depression; p less than 0.01). After felodipine, 13 patients continued to show ST-segment depression during overbreathing, together with an increase in rate pressure product (from 107 +/- 24 at baseline to 158 +/- 46 mm Hg x beats/min/100 at the onset of electrocardiographic changes; p less than 0.01). In group II, all 12 patients showed ST-segment depression during recovery after placebo, with a rate pressure product comparable to baseline conditions (112 +/- 35 at baseline vs 102 +/- 27 mm Hg x beats/min/100 at the onset of ST-segment depression; difference not significant). After felodipine, no patient developed ST-segment depression or chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphologic changes induced by acetylcholine infusion in normal and atherosclerotic coronary arteries.

Low doses of acetylcholine induce "endothelium-dependent" dilatation in normal coronary arteries and constriction of diseased vessels. This study investigated morphologic changes induced by perfusion of normal and diseased coronary arteries with low and high doses of acetylcholine. Vessels were excised from a series of beating hearts explanted at transplantation for idiopathic dilated cardiomyopathy and coronary artery disease. Coronary arteries from other explanted hearts, perfused with saline solution under similar conditions were taken as controls. Samples were studied using conventional histopathologic and immunohistochemical methods. Coronary arteries were grouped according to presence or absence of histologically detectable structural modifications of any type and extent. Low doses of acetylcholine induced changes in all but 1 structurally diseased coronary artery, whereas no change was induced in any but 1 histologically normal coronary artery. High doses of acetylcholine induced contraction changes in both normal and diseased vessels. Changes observed in the wall of the contracted vessels were: (1) endothelial cell contraction with protruding nuclei and detachment of their intercellular junctions with exposure of subjacent collagen to flow, (2) contraction of plaque smooth muscle cells, (3) formation of cushions protruding into vessel lumens causing blunt microchannels. Contraction in both intimal and plaque cells occurred even in diseased vessel segments with intimal denudation. These effects seemed to be dose-dependent in structurally normal vessels because low doses of acetylcholine did not produce any morphologically detectable changes in histologically normal coronary arteries, while low doses of acetylcholine induced similar reactions in vessels affected by both atherosclerosis and subintimal fibrocellular thickening.

Influence of elastic recoil on restenosis after successful coronary angioplasty in unstable angina pectoris.

The elastic behavior of the dilated coronary vessel has been reported to affect the immediate results of coronary angioplasty. To determine whether elastic recoil may also influence the long-term restenosis process, 98 consecutive patients with unstable angina and 1-vessel disease were studied. An automated coronary quantitative program was used for the assessment of balloon and coronary luminal diameters. Elastic recoil was defined as the percent reduction between minimal balloon diameter at the highest inflation pressure and minimal lesion diameter immediately after coronary angioplasty. Follow-up coronary arteriography was performed 8 to 12 months after the procedure in all patients. The mean elastic recoil averaged 17.7 +/- 16% and was correlated to the degree of residual stenosis immediately after coronary angioplasty (r = 0.64; p < 0.001). Restenosis, defined as > 50% diameter stenosis at follow-up, developed in 53 patients (54%). There was no correlation between the degree of elastic recoil and the changes in minimal lesion diameter observed during follow-up, whereas a positive correlation between the amount of elastic recoil and the incidence of restenosis was documented (r = 0.84; p < 0.05). Thus, the elastic properties of the dilated vessel do not influence the active process of restenosis. However, because elastic recoil negatively influences the initial results of angioplasty, it is more likely that further reductions in lumen diameter during follow-up can reach a threshold of obstruction considered critical for a binary definition of restenosis.

Correlation between clinical and morphologic findings in unstable angina.

This study was undertaken to verify the hypothesis that the discrepant findings in published reports on the prevalence of thrombus in unstable angina depend on the inclusion of different clinical subsets in the various studies. We therefore correlated the clinical characteristics of patients included under the label of unstable angina with the morphologic features assessed by coronary angiography and intravascular ultrasound, and with histopathologic findings of atherectomy specimens. Fifty-eight patients with unstable angina (class B of the Braunwald classification) undergoing coronary arteriography followed by either coronary angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied. Fifteen patients were in class IB and 43 were in class II to IIIB. Among these 43 patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had ST-segment depression, and 26 developed negative T waves on the baseline electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting chest pain. Intravascular ultrasound examination of the culprit lesion was performed in 43 patients before the interventional procedure, and histopathologic analysis of atherectomy specimens was performed in 38 patients. Complex lesion morphology by angiography was observed in 31 patients (53%) without any significant relation to various clinical subsets. Patients in Braunwald class IB had more calcific plaques than patients in class II to IIIB (p < 0.001). Among patients with angina at rest, those with negative T waves on the baseline ECG, as well as those with transient ST elevation during pain, had a significantly higher incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy specimens revealed acute coronary lesions (thrombus and/or intraplaque hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was significantly higher in patients with than without negative T waves on the baseline ECG (p = 0.005), and increased further when negative T waves were combined with ST elevation during pain (p = 0.001). Multivariate analysis revealed that the presence orf negative T waves on the baseline ECG was the only explanatory variable related to the presence of acute coronary lesions by histology (p = 0.03). Patient subsets included in the broad spectrum of unstable angina have different morphologic features and incidence of acute coronary lesions by histology. These data provide an explanation for the discrepant findings in published reports on the relevance of thrombus formation in the pathogenesis of unstable angina.