Effects of hypercholesterolaemia on physiological recruitment of coronary vascular reserve in swine.

1. The endothelium participates in the regulation of coronary vascular tone. As evidence exists from studies performed on epicardial vessels that hypercholesterolaemia impairs endothelial function, we tested the hypothesis that hypercholesterolaemia impairs coronary vascular reserve in an intact animal. 2. Domestic swine, maintained on a regular (n = 9) or a 2% high-cholesterol (n = 9) diet for 3 months were instrumented with a catheter in the left atrium for microsphere injection, a catheter in the anterior interventricular vein for venous sampling and an 82% stenosis in the left anterior descending artery. Papaverine was used to determine coronary vascular reserve. Regional coronary flow as reflected by perfusion (microsphere measurement), lactate consumption, oxygen consumption and haemodynamics were obtained at baseline, after 10 mg of papaverine and after atrial pacing at a rate of 120 beats/min and 150 beats/min. 3. Cholesterol was elevated in animals on the high cholesterol diet (350 +/- 50 mg/dl versus 99 +/- 10 mg/dl, P < 0.001). Baseline haemodynamics were similar between groups. Baseline transmural flow and its augmentation with papaverine were comparable in the two groups in the control (circumflex) and stenosed (left anterior descending artery) zones. In both groups, perfusion increased in the control zone in response to increased oxygen demand, whereas in the stenosis zone no increase was observed in either group (P not significant for normal versus high cholesterol diet). Endocardial flow reserve in the stenosis zone was exhausted in both groups. Epicardial flow in the stenosis zone increased significantly in the normal (P < 0.02) but not in the hypercholesterolaemic animals (P not significant). 4. The endocardial/epicardial ratio in the control zone at baseline revealed greater endocardial dominance in the normal compared with the hypercholesterolaemic animals (1.35 versus 1.10, P < 0.01). With papaverine, similar ratios indicated a similar reserve potential in both groups. During increased oxygen demand, normal animals continued to demonstrate endocardial dominance whereas it diminished in the hypercholesterolaemic group. In the stenosis zone, endocardial blood flow dominated at baseline in the normal animals and to a lesser extent in the hypercholesterolaemic animals (1.30 versus 1.10, P = 0.10). During increased oxygen demand, endocardial dominance decreased significantly in both groups of animals; however, it remained greater than 1.0 only in the normal animals. 5. Exposure to elevated cholesterol levels did not impair an animal's ability to augment coronary blood flow in response to an increase in oxygen demand. In contrast to this lack of effect on recruitment of coronary reserve, regional coronary blood flow was altered in the hypercholesterolaemic animals.

Augmentation of coronary blood flow by ACE inhibition: role of angiotensin and bradykinin.

Inhibition of the angiotensin converting enzyme (ACE) is known to enhance coronary blood flow via partial suppression of angiotensin II and potentiation of bradykinin. The purpose of these experiments was to evaluate the contribution of each of these mechanisms to the ACE inhibition induced changes in blood flow in myocardial regions perfused by intact or stenotic coronary arteries. Seven domestic swine were submitted to an 82% stenosis of the left anterior descending artery with the circumflex artery left intact to serve as control area. Regional coronary blood flows were measured by the radioactive microsphere technique in the total area perfused by each coronary artery and in the subepicardial and subendocardial regions of each area separately, at rest and after treatments with captopril, losartan and a bradykinin antagonist given consecutively. We found a significant increase of total flow in both the stenotic and intact areas after captopril. Losartan caused a significant fall in systemic blood pressure with no further changes in overall coronary blood flow and the bradykinin antagonist produced a small but nonsignificant decline in total coronary flow. However, further separate analysis of subregions showed that subendocardial regions had a sharper increase in flow after captopril, and a significantly greater decline after bradykinin inhibition than subepicardial regions, whereas losartan tended to shunt blood from the subendocardial to the subepicardial regions. The results indicate that augmentation of coronary blood flow after ACE inhibition is not further enhanced by angiotensin II blockade and is in part mediated via potentiation of endogenous bradykinin, which exerts a preferential vasodilatory effect on the subendocardial regions of the myocardium.

Comparison of patients with < 60% to > or = 60% diameter narrowing of the myocardial infarct-related artery after thrombolysis. The TIMI Investigators.

The purpose of this study was to analyze angiographic findings, clinical course, and follow-up data on 1,752 patients who underwent protocol cardiac catheterization 18 to 48 hours after enrollment in the Thrombolysis in Myocardial Infarction (TIMI) II pilot and randomized trial: 244 patients (14.0%) had < 60% diameter stenosis in the infarct-related artery and TIMI grade 2 or 3 flow, 1,249 (71.2%) had a narrowing > or = 60% in diameter with TIMI grade 2 or 3 flow, and 259 patients (15%) had TIMI grade 0 or 1 flow (total occlusion). Patients with < 60% narrowing in the infarct-related artery were younger (p < 0.001) and more likely to be current smokers than those with more severe narrowings (p < 0.003). Patients with < 60% diameter stenosis in the infarct-related artery were more likely to have a predischarge radionuclide ejection fraction > 55% (p < 0.001) than were other patient groups. The 1-year mortality rate of patients with < 60% diameter stenosis in the infarct-related artery was 1.6% compared with 4.4% for patients with stenosis > or = 60% and TIMI grade 2 or 3 flow (p = 0.05) and 7.0% for patients with total occlusion (p = 0.004). Patients with stenosis < 60% in the infarct-related artery 18 to 48 hours after thrombolytic therapy have a good prognosis. Infarct artery status predicts predischarge ejection fraction and 1-year mortality.

Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial.

OBJECTIVES: The purpose of this study was to determine the incidence of ventricular tachycardia and fibrillation without hypotension or heart failure after treatment with recombinant tissue-type plasminogen activator (rt-PA), anatomic correlates of their development, the effect of immediate intravenous metoprolol on their occurrence and the outcome of patients with these arrhythmias. BACKGROUND: Malignant arrhythmias after thrombolytic therapy have been reported to occur as a result of coronary reperfusion, which is associated with reduced mortality in patients receiving thrombolytic therapy. METHODS: We analyzed data from 2,546 patients in the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial without congestive heart failure or hypotension during the 1st 24 h after study entry. Forty-nine patients (1.9%) developed sustained ventricular tachycardia or ventricular fibrillation within 24 h of study entry (group 1), and 2,497 patients (98.1%) did not (group 2). RESULTS: Baseline characteristics and admission laboratory values were similar in the two groups. In patients undergoing protocol angiography 18 to 48 h after rt-PA, the infarct-related artery was patient in a greater percent of group 2 patients (87% [1,015 of 1,169]) than group 1 patients (68% [15 of 22], p = 0.01), although angiography was performed less frequently in group 1 than in group 2. More group 1 than group 2 patients died within 21 days (20.4%) (1.6%, p < 0.001). For patients surviving to 21 days, there was no difference in mortality between patients in the two groups in the following year. CONCLUSIONS: Ventricular tachycardia and fibrillation are not markers for reperfusion after thrombolytic therapy. These arrhythmias are associated with occlusion, not patency, of the infarct-related artery. Early mortality is increased in patients who develop ventricular tachycardia and fibrillation, even in the absence of congestive heart failure and hypotension.

Frequency and significance of right ventricular dysfunction during inferior wall left ventricular myocardial infarction treated with thrombolytic therapy (results from the thrombolysis in myocardial infarction [TIMI] II trial). The TIMI Research Group.

To determine the effect of thrombolytic therapy on the frequency of right ventricular (RV) dysfunction, and whether RV dysfunction is a risk factor for morbidity and mortality after discharge from the hospital, 1,110 patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial with acute inferior wall left ventricular myocardial infarction were studied. RV dysfunction was defined as an RV wall motion abnormality on equilibrium radionuclide ventriculography performed a mean of 9 days after admission to the hospital. Fifty-eight patients (5%) had RV dysfunction. Baseline clinical characteristics among patients with and without RV dysfunction were similar. However, patients with RV dysfunction had a lower mean left ventricular ejection fraction (51.2 +/- 1.2% vs 55.5 +/- 0.3%; p < 0.001) and a greater frequency of in-hospital complications. Angiographic data from patients undergoing protocol catheterization 18 to 48 hours after hospital admission show that the infarct-related artery was more likely to be occluded in those with RV dysfunction (48% [15 of 31] vs 14% [68 of 495]; p < 0.001). There was no difference in the frequency of multivessel disease between the 2 groups. In patients with RV dysfunction in whom radionuclide ventriculography was repeated 6 weeks after hospital discharge, RV wall motion abnormalities persisted in only 18% (8 of 45). Mortality in the year after discharge was 3.5% (2 of 58) among patients with RV dysfunction compared with 1.7% (18 of 1,052; p = NS) among those without RV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Invasive versus conservative strategy after thrombolytic therapy for acute myocardial infarction in patients with antecedent angina. A report from Thrombolysis in Myocardial Infarction Phase II (TIMI II).

OBJECTIVES: This study was designed to assess the possibility that a subgroup of patients at high risk for recurrent ischemia and reinfarction after thrombolytic therapy might benefit from early intervention. BACKGROUND: The Thrombolysis in Myocardial Infarction Phase II (TIMI II) study recently concluded that an obligatory invasive strategy after thrombolytic therapy offered no advantage over a more conservative strategy. METHODS: Data from the 3,534 patients enrolled in the TIMI II trial were analyzed to determine whether a history of antecedent angina before myocardial infarction identifies patients at high risk for subsequent ischemia and whether these patients might benefit from an invasive strategy. RESULTS: Within the TIMI II population, antecedent angina identified patients at increased risk for recurrent chest pain in the hospital (32.3% vs. 22.1%, p < 0.001) and recurrent infarction during the 1st year of follow-up (11.2% vs. 7.9%, p = 0.001) compared with that of patients without antecedent angina. Among patients assigned to the invasive strategy, coronary arteriography revealed that those with antecedent angina had a more severe residual stenosis of the infarct-related artery after thrombolytic therapy (77.1 +/- 0.7% vs. 73.0 +/- 0.9%, p < 0.001) and more multivessel disease (37.9% vs. 26.4%, p < 0.001). The clinical outcome of the patients with antecedent angina assigned randomly to either the invasive or the conservative strategy were compared. The invasive strategy patients had a slightly lesser incidence of recurrent chest pain in the hospital (29.9% vs. 34.8%, p = 0.13) and more negative (normal) findings on exercise tolerance tests (24.7 vs. 18.9%, p = 0.003), but there was no difference between the treatment strategies in the end point variable of recurrent myocardial infarction or death. CONCLUSIONS: These data demonstrate that antecedent angina identifies patients at increased risk for recurrent ischemic events after thrombolytic therapy. However, similar to the results for the overall population, the invasive strategy does not alter the risk of reinfarction or death compared with the conservative approach.

Prediction of risk for hemodynamic compromise during percutaneous transluminal coronary angioplasty.

The availability of circulatory support devices has increased the importance of accurately identifying patients at risk for hemodynamic compromise during percutaneous transluminal coronary angioplasty (PTCA). Accordingly, prospective evaluation of 3 criteria to predict hemodynamic compromise (defined as a decrease in systolic blood pressure > or = 20 to < 90 mm Hg during balloon inflation) in 157 patients (group A) undergoing PTCA was performed. Left ventricular ejection fraction < 35% had a sensitivity of 13% and a specificity of 95%. Greater than 50% of the myocardium at risk was associated with a sensitivity of 31% and a specificity of 85%. The angiographer's assessment of high risk for hemodynamic compromise had the highest sensitivity of 56% and a specificity of 86%. The clinical and angiographic characteristics of these patients were reviewed to identify risk factors retrospectively. Multivariate analysis of 28 variables identified multivessel disease, diffuse disease, myocardium at risk, and stenosis before PTCA as independent predictors of hemodynamic compromise. With use of this analysis, a 13-point weighted scoring system was created based on the regression of coefficients of the variables. Defining high risk for hemodynamic compromise as a risk score > or = 4, the sensitivity of this criterion in group A patients was 81% and the specificity was 74%. The scoring system was then prospectively applied to 61 consecutive patients (group B) undergoing PTCA. In using a risk score > or = 4 to define high risk, this scoring system had a sensitivity of 92% and a specificity of 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and prognostic implications of heart block complicating inferior myocardial infarction treated with thrombolytic therapy: results from TIMI II.

OBJECTIVES: The aim of this study was to determine the incidence and significance of second- or third-degree heart block among patients with inferior myocardial infarction treated with thrombolytic therapy. BACKGROUND: Data from the prethrombolytic era suggest that heart block occurs in approximately 20% of patients with acute inferior myocardial infarction and is associated with a marked increase in mortality. Little is known about the incidence and prognostic implications of heart block among patients receiving thrombolytic therapy. METHODS: We studied 1,786 patients with acute inferior myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) II Trial who received recombinant tissue-type plasminogen activator (rt-PA) within 4 h of the onset of symptoms. RESULTS: Heart block occurred in 214 patients (12%); 113 (6.3%) had heart block on presentation and 101 (5.7%) developed heart block in the 24 h after treatment with rt-PA. Patients with heart block at entry were slightly older and a greater proportion had cardiogenic shock. The 21-day mortality rate among patients with heart block at entry was 7.1% (8 of 113), compared with 2.7% (45 of 1,673) among patients without heart block at study entry (relative risk 2.6, p = 0.007). However, heart block was not independently associated with 21-day mortality after adjustment for other variables, including shock. Mortality and other adverse cardiac events in the following year were similar among patients with and without heart block. Among patients without heart block at study entry, coronary angiography among patients randomly assigned to coronary catheterization 18 to 48 h after admission revealed that the infarct-related artery was occluded in 28.2% (11 of 39) of patients who developed heart block versus 15.5% (112 of 723) of patients without heart block (p = 0.04). The 21-day mortality rate was increased among patients in whom heart block developed after thrombolytic therapy (9.9% [10 of 101] versus 2.2% [35 of 1,572] of patients without heart block, relative risk 4.5, p less than 0.001). Analysis of the increased mortality among patients who developed heart block suggests that mortality was due to severe cardiac dysfunction; no patient was considered to have died as a result of the heart block or its treatment. CONCLUSIONS: Heart block is common among patients with inferior infarction given thrombolytic therapy and is associated with increased mortality. These clinical and anatomic data provide insight into the mechanism of heart block and increased mortality among such patients.

The degree of revascularization and outcome after multivessel coronary angioplasty.

Incomplete revascularization is a common occurrence following angioplasty (PTCA) in patients with multivessel disease. To determine the short-term and long-term consequences of incomplete revascularization and the influence of the functional nature of the incomplete revascularization, 139 consecutive patients with multivessel disease were analyzed: 72 were completely revascularized and 67 had incomplete revascularization. The former patients had a lower incidence of prior myocardial infarction (MI) and prior bypass surgery (CABG). All patients had at least one lesion successfully dilated. In-hospital complications were insignificantly greater in incompletely revascularized patients compared with completely vascularized patients (mortality 3% versus 1%, MI 11% versus 4%, and emergency surgery 5% versus 0%). After 1 year of follow-up, incompletely revascularized patients had similar outcomes (mortality 6% versus 3%, MI 13% versus 7%, CABG 18% versus 15%, and repeat PTCA 19% versus 31%). The degree of incomplete revascularization was categorized as functionally adequate if all stenoses in bypassable vessels supporting viable myocardium were successfully dilated. Significantly fewer adverse events (death, MI, or CABG) occurred in the functionally adequate group than in the functionally inadequate group (27% versus 6%, p less than 0.04). This study demonstrates that incompletely revascularized patients have a favorable 1-year outcome and that patients with incomplete but functionally adequate revascularization have long-term results comparable with those of patients with complete revascularization. This study emphasizes the need to assess the functional significance of a stenosis when considering incomplete revascularization in a patient with multivessel disease.

Results of coronary angioplasty of chronic total occlusions (the National Heart, Lung, and Blood Institute 1985-1986 Percutaneous Transluminal Angioplasty Registry).

There has been increasing application of coronary angioplasty to patients with chronic total occlusions. The acute and long-term outcome in 271 patients after coronary angioplasty (142 single and 129 multiple stenoses) of a total occlusion was compared with 1,429 patients undergoing angioplasty of subtotal (less than or equal to 99% stenosis) occlusions (885 single and 544 multilesion) participating in the 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Baseline characteristics were similar for each lesion group except for a higher incidence of prior myocardial infarction and left ventricular dysfunction (ejection fraction less than 50%) in patients with total occlusion. Major complications (death, myocardial infarction or emergency bypass surgery) were similar (p = not significant) between patients with total and subtotal occlusions for single (6 vs 7%) and multilesion angioplasty (9 vs 6%). At 2 years, after making adjustments for baseline variables, patients with a total occlusion had a significantly increased risk of death compared with those with subtotal occlusion. There were no significant differences in cumulative event rates for myocardial infarction or bypass surgery. Approximately three-fourths of patients in each group were free of angina at 2 years. In conclusion, angioplasty of chronic total occlusions is associated with a similar acute complication rate. Despite similar relief of anginal symptoms, patients in the total occlusion group have a higher 2-year mortality.

Experience with low-dose intracoronary recombinant tissue-type plasminogen activator for nonacute total occlusions before percutaneous transluminal coronary angioplasty.

The primary success rate for angioplasty of total occlusions is significantly worse than for subtotal lesions. Pharmacologic recanalization of total occlusions before angioplasty has the potential to improve the primary success rate. To determine the ability of recombinant tissue-type plasminogen activator (rt-PA) to recanalize occlusive thrombi before elective percutaneous transluminal coronary angioplasty, 12 patients with total occlusions, 100% obstruction and Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow, and 5 with functional total occlusions, severe stenoses and TIMI grade 1 flow received an intracoronary infusion of rt-PA. The first 10 patients received 0.2 mg/min for 90 minutes, and the next 7 patients received 0.4 mg/min for 60 minutes. Flow improved by greater than or equal to 1 TIMI grade in 11 patients. Mean TIMI flow improved from 0.3 +/- 0.5 to 1.5 +/- 1.2 (p less than 0.0001). There was a significant improvement in severity of stenosis after rt-PA infusion by both digital caliper (99 +/- 2 vs 84 +/- 16%; p less than 0.0001) and quantitative videodensitometric area assessment (99 +/- 3 vs 94 +/- 6%; p less than 0.004). Angioplasty was successful in 16 of 17 patients (94%). There were 2 out-of-laboratory abrupt closures at 4 days; both were medically treated and 1 had a small myocardial infarction. Only 1 patient had a bleeding complication significant enough to need a transfusion. It is concluded that low-dose intracoronary rt-PA is effective at lysing thrombi less than 3 weeks old. This approach warrants further investigation since it may significantly improve the primary success rate of percutaneous transluminal coronary angioplasty in patients with occlusive thrombus.

Prior restenosis predicts restenosis after coronary angioplasty of a new significant narrowing.

To determine the influence of a history of restenosis on subsequent restenosis after percutaneous transluminal coronary angioplasty (PTCA) of a new significant narrowing, the records of 100 patients who underwent successful PTCA at another site ("new narrowing PTCA") greater than or equal to 2 months after successful initial PTCA were retrospectively reviewed. Patients were grouped according to whether initial PTCA resulted in restenosis, which was determined by angiographic follow-up greater than or equal to 3 months after initial PTCA. Patients in group 1 did not have restenosis after initial PTCA (n = 50), whereas patients in group 2 did (n = 40). All patients were followed for recurrent symptoms, with serial exercise tests, for greater than or equal to 6 months after new narrowing PTCA. Clinically suspected and angiographically confirmed restenosis occurred in 11 of 50 (22%) patients and 12 of 63 (19%) narrowings in group 1, and in 20 of 40 (50%) patients and 22 of 48 (46%) narrowings in group 2 (p less than 0.01 for patients, p less than 0.002 for narrowings). Multivariate analysis identified that prior restenosis (p less than 0.02, odds ratio 3.4), left anterior descending artery location of stenosis (p less than 0.04, odds ratio 3.0), and severity of stenosis before PTCA (p less than 0.02, odds ratio 1.8) were independently associated with restenosis after new narrowing PTCA. In conclusion, prior restenosis is an independent risk factor for subsequent restenosis after new narrowing PTCA.

Detection of intracoronary fibrin degradation after coronary balloon angioplasty.

Intracoronary thrombus formation may be involved in the pathogenesis of arterial closure after coronary angioplasty and may contribute to restenosis. It is hypothesized that, unlike markers of platelet activation and fibrin formation, D-dimer, a product of plasmin-mediated proteolysis of cross-linked fibrin, is not subject to significant catheter-induced artifact and could be used to study intracoronary fibrin degradation during angioplasty. No significant difference in D-dimer levels was noted in serial plasma samples obtained from an 8Fr arterial sheath and the wire lumen of an angioplasty balloon catheter, indicating that sampling through the catheter lumen did not induce artifactual D-dimer elevations. Translesion (proximal and distal to the lesion) coronary blood samples were collected in 31 patients undergoing elective coronary angioplasty pretreated with aspirin, dipyridamole and heparin. In 20 of those in whom translesion coronary samples for plasma D-dimer levels (mean +/- standard deviation) were collected before balloon dilation, there was no evidence of ongoing intracoronary fibrinolysis (proximal D-dimer levels, 289 +/- 145 ng/ml; distal, 299 +/- 156 ng/ml; difference not significant). After coronary angioplasty (n = 31), there was a relatively small, but significant (p less than 0.001) increase (45 +/- 71 ng/ml) in translesional D-dimer levels (proximal, 396 +/- 223 ng/ml; distal, 441 +/- 257 ng/ml). The results from this study suggest (1) D-dimer levels are not subject to significant catheter-induced artifact and may be useful for assessment of intracoronary fibrin metabolism, and (2) intracoronary degradation of fibrin can be detected after (but not before) routine coronary angioplasty despite pretreatment with antithrombotic therapy, presumably in response to balloon-induced arterial injury and fibrin formation.

Outcome after major dissection during coronary angioplasty using the perfusion balloon catheter.

Coronary artery dissection is an infrequent but serious complication of coronary angioplasty that can lead to periprocedural vessel occlusion, emergency bypass surgery, myocardial infarction or death. Recently, a perfusion balloon catheter was developed that permits passive perfusion of blood through the central lumen of the catheter. It enables prolonged balloon inflations to be performed and has been used to provide distal blood flow after coronary occlusion. To evaluate the effectiveness of the perfusion balloon catheter in patients with major coronary dissections, 36 consecutive patients treated with the perfusion balloon catheter were compared with 46 consecutive patients treated before its availability. The 2 groups were similar in terms of clinical, angiographic and initial procedural characteristics. Use of the perfusion balloon catheter permitted a significantly longer inflation than standard balloon inflation (average 18 +/- 5 min). Angiographic success was significantly greater with the perfusion balloon catheter (84 vs 62% for conventional therapy), whereas complications were markedly reduced (48 vs 78%). With the perfusion balloon catheter there were fewer deaths (2 vs 6%), myocardial infarctions (14 vs 40%) and emergency bypass operations (11 vs 25%). The findings of this retrospective comparison demonstrate that the perfusion balloon catheter is effective for the management of major dissections after coronary angioplasty. The use of the perfusion balloon catheter should be considered when a major coronary dissection occurs and when emergency bypass surgery is contemplated.

Tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty: one-year TIMI phase II pilot results. TIMI Investigators.

The TIMI phase II pilot study enrolled 288 patients with acute myocardial infarction who were treated with recombinant tissue plasminogen activator (rt-PA) within 4 hours of symptom onset and who were assigned to coronary angioplasty of the infarct-related vessel 18 to 48 hours after rt-PA treatment. The patients were followed to ascertain (1) vital status; (2) whether they suffered a recurrent myocardial infarction; (3) whether they received coronary angioplasty or bypass grafting; and (4) whether they were rehospitalized for a cardiac event. Risk factors for these events or combination of these events were identified and reported. The estimated 6-week, 6-month, and 1-year cumulative event rate of death or myocardial infarction was 9.1 +/- 1.7%, 12.9 +/- 2.0%, and 13.6 +/- 2.0%, respectively. With the exception of repeat hospital admissions, most of the above cardiac events occurred early during the patients' follow-up course. Cox proportional hazard analyses revealed that continuing chest pain after rt-PA administration, history of congestive heart failure, low systolic blood pressure at the time of initial evaluation, and history of hypertension increased the risk of death or recurrent myocardial infarction, while a history of chest discomfort at baseline evaluation and older age was predictive of future hospitalization or a revascularization procedure.

Antecedent angina: a predictor of residual stenosis after thrombolytic therapy.

Patients with a significant residual stenosis after thrombolytic therapy are believed by many to be at increased risk for repeat ischemic events and may be candidates for prompt angiography and revascularization. To test the hypothesis that patients with antecedent angina (Canadian classes I to IV, greater than or equal to 24 h before myocardial infarction) are more likely to have a significant residual stenosis (greater than or equal to 60% diameter reduction) than are those without antecedent angina, the coronary angiograms of 82 consecutive patients undergoing routine angiography after thrombolytic therapy were reviewed. Compared with the patients without antecedent angina, the group with antecedent angina had an increased mean stenosis (74% versus 58%) and more multivessel disease (44% versus 5%). The sensitivity and specificity of a clinical history of antecedent angina predicting the presence of a significant residual stenosis were 75% and 96%, respectively; the positive predictive accuracy was 98%. These data suggest that antecedent angina can be used to identify a high risk subgroup whose condition may warrant routine coronary angiography.

Outcome in patients with recurrent restenosis after percutaneous transluminal balloon angioplasty.

The records of 1162 consecutive patients undergoing their first percutaneous transluminal coronary angioplasty at a centre between March 1980 and June 1987 were reviewed. Initial angioplasty was successful in 1011 patients (87%). In 202 (20%) symptomatic restenosis developed. Of these, 196 were treated with redilatation; this was successful in 181 (92%). After a second dilatation, restenosis developed in 47 patients (26%). Of these, 41 (87%) were treated with a third angioplasty, with primary success in 38 (93%). A further restenosis developed in 13 of these 38 patients (34%). Eight patients were treated with a fourth angioplasty with restenosis in four (50%). Two of these four patients underwent a fifth angioplasty (with continuing success at long term follow up in both). Overall, 14 of the 47 (30%) patients who developed restenosis twice were eventually treated with coronary bypass surgery. Most patients (33), however, were treated only with repeated angioplasties. Of these 33 patients, 27 were treated with a third angioplasty, four with a fourth procedure, and two with a fifth. Twenty-nine (88%) were symptom free at a mean follow up of 28 (range 8 to 86) months. The combined success rate for a third, fourth, and fifth angioplasty was 94%. These data suggest that most patients with recurrent restenosis after angioplasty may be managed successfully and safely with repeated redilatations.

Factors predicting recurrent restenosis after percutaneous transluminal coronary balloon angioplasty.

To identify factors that predict a second restenosis after repeat percutaneous transluminal coronary balloon angioplasty (PTCA), the records of 196 consecutive patients undergoing redilation for treatment of a first restenosis were reviewed. Repeat PTCA was successful in 181 (92%) of these patients. After a successful second PTCA, 47 patients (26%) developed a second restenosis (recurrent restenosis group, group 1) and 134 (single restenosis group, group 2) did not. The 2 patient groups were compared with respect to clinical, angiographic and procedural factors at second PTCA. Univariate correlates of a second restenosis were younger age (54 +/- 10 vs 57 +/- 9 years, p less than 0.05), interval less than 60 days between initial PTCA and recurrence of anginal symptoms (55% of patients in group 1 vs 25% in group 2, p = 0.001), a greater number of inflations (6.3 +/- 4.2 vs 4.4 +/- 2.5, p less than 0.005) and a shorter maximal balloon inflation time (49 +/- 26 vs 69 +/- 36 seconds, p = 0.0006). With multivariate analysis, the 2 factors that emerged as independent predictors of recurrent restenosis were recurrence of symptoms less than 60 days after initial PTCA (p less than 0.004) and a greater number of inflations (p less than 0.04). These data suggest that younger age and rapid recurrence of anginal symptoms after first PTCA predict an increased likelihood that a second restenosis will occur after repeat PTCA and that certain procedural factors, in particular the greater number of balloon inflations and a shorter maximal balloon inflation time, may play an important role in the development of recurrent restenosis.

Role of endogenous prostacyclin in myocardial blood flow regulation distal to a severe coronary stenosis.

To test the hypothesis that endogenous prostacyclin is required to maintain reduced arteriolar tone distal to a severe coronary arterial stenosis under basal conditions and during challenge with a vasoconstrictor eicosanoid such as thromboxane A2 10 closed chest, domestic swine were prepared with an artificial stenosis, which reduced the luminal diameter of the left anterior descending coronary artery by 80%. Haemodynamic variables, regional myocardial blood flow (microsphere method), and lactate metabolism were measured at control (1); after infusion of U46619 (thromboxane A2 mimetic) distal to the stenosis at 1 microgram.min-1 for 10 min and 5 micrograms.min-1 for 10 min; at control (2); after indomethacin infusion distal to the stenosis; and after repeat infusion of U46619. At the end of the study the animal hearts were removed and their coronary vessels harvested for in vitro determination of prostacyclin (PGI2) production. Regional myocardial blood flow in all layers of the heart distal to the stenosis did not change compared with control during the initial 1 microgram.min-1 dose of U46619 but was reduced significantly after the 5 micrograms.min-1 dose (approximately 20% vs control). Distal zone flow (all layers) returned to baseline at control (2) and remained unchanged after indomethacin infusion. Although distal zone flows were reduced significantly in response to the second 5 micrograms.min-1 dose, the reduction in each layer after indomethacin was comparable to that observed with the 5 micrograms.min-1 dose before indomethacin infusion. Finally, the in vitro production of PGI2 by coronary vessels was considerably impaired by indomethacin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of serotonin on myocardial blood flow in the presence and absence of a coronary arterial stenosis: observations in domestic swine.

This study tested the hypothesis that 5-HT may impair coronary flow regulation by inappropriately increasing arteriolar tone in the coronary circulation. Ten closed chest, domestic swine were studied both in the presence and in the absence of a severe artificial intraluminal coronary stenosis. A 5-French micromanometer catheter with fluid lumen was placed in the left anterior descending coronary artery and used to record pressure and infuse 5-HT (40 and 100 micrograms/min) into the coronary circulation. For the stenosis phase of the protocol the catheter was embedded in the artificial stenosis. Hemodynamics, regional myocardial blood flow (microsphere technique), coronary vascular resistance, lactate consumption, and oxygen metabolism were measured at control and at 5 min of each 5-HT dose. In the absence of coronary artery stenosis (i.e., full vasodilatory reserve), there was no change in regional myocardial blood flow or coronary vascular resistance during 5-HT infusion. In the presence of a severe coronary stenosis (i.e., limited vasodilator reserve) 5-HT produced a significant (P less than 0.05) decrease versus control in the distal left anterior descending: circumflex zone endocardial blood flow ratio (0.63 +/- 0.19, mean +/- 1 SD, to 0.55 +/- 0.15) and a significant (P less than 0.05) increase versus control in endocardial (50.6 +/- 16.6 to 61.2 +/- 19.8 mm Hg/ml/min/g) and transmural (49.9 +/- 9.5 to 57.2 +/- 12.8) coronary vascular resistance. Thus, 5-HT does not impair coronary flow regulation when full vasodilatory reserve is present. When coronary vasodilatory reserve is impaired by the presence of a severe proximal stenosis, 5-HT causes modest impairment of endocardial flow regulation.