Richard S. Stack

A Randomized Trial of Immediate versus Delayed Elective Angioplasty after Intravenous Tissue Plasminogen Activator in Acute Myocardial Infarction

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.

Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group.

To determine the clinical consequences of reocclusion of an infarct-related artery after reperfusion therapy, we evaluated 810 patients with acute myocardial infarction. Patients were admitted into four sequential studies with similar entry criteria in which patency of the infarct-related artery was assessed by coronary arteriography 90 minutes after onset of thrombolytic therapy. Successful reperfusion was established acutely in 733 patients. Thrombolytic therapy included tissue-type plasminogen activator (t-PA) in 517, urokinase in 87, and a combination of t-PA and urokinase in 129 patients. All patients received aspirin, intravenous heparin and nitroglycerin, and diltiazem during the recovery phase. A repeat coronary arteriogram was performed in 88% of patients at a median of 7 days after the onset of symptoms. Reocclusion of the infarct-related artery occurred in 91 patients (12.4%), and 58% of these were symptomatic. Angiographic characteristics at 90 minutes after thrombolytic therapy that were associated with reocclusion compared with sustained coronary artery patency were right coronary infarct-related artery (65% versus 44%, respectively) and Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1 (21% versus 10%, respectively) before further intervention. Median (interquartile value) degree of stenosis in the infarct-related artery at 90 minutes was similar between groups: 99% for reoccluded (value, 90/100%) compared with 95% for patent (value, 80/99%). Patients with reocclusion had similar left ventricular ejection fractions compared with patients with sustained patency at follow-up. However, patients with reocclusion at follow-up had worse infarct-zone function at -2.7 (value, -3.2/-1.8) versus -2.4 (SD/chord) (value, -3.1/-1.3) (p = 0.016). The recovery of both global and infarct-zone function was impaired by reocclusion of the infarct-related artery compared with maintained patency; median delta ejection fraction was -2 compared with 1 (p = 0.006) and median delta infarct-zone wall motion was -0.10 compared with 0.34 SD/chord (p = 0.011), respectively. In addition, patients with reocclusion had more complicated hospital courses and higher in-hospital mortality rates (11.0% versus 4.5%, respectively; p = 0.01). We conclude that reocclusion of the infarct-related artery after successful reperfusion is associated with substantial morbidity and mortality rates. Reocclusion is also detrimental to the functional recovery of both global and infarct-zone regional left ventricular function. Thus, new strategies in the postinfarction period need to be developed to prevent reocclusion of the infarct-related artery.

Continuing evolution of therapy for coronary artery disease : initial results from the era of coronary angioplasty

BACKGROUND Survival after coronary artery bypass graft surgery (CABG) and medical therapy in patients with coronary artery disease (CAD) has been studied in both randomized trials and observational treatment comparisons. Over the past decade, the use of coronary angioplasty (PTCA) has increased dramatically, without guidance from either randomized trials or prospective observational comparisons. The purpose of this study was to describe the survival experience of a large prospective cohort of CAD patients treated with medicine, PTCA, or CABG. METHODS AND RESULTS The study was designed as a prospective nonrandomized treatment comparison in the setting of an academic medical center (tertiary care). Subjects were 9263 patients with symptomatic CAD referred for cardiac catheterization (1984 through 1990). Patients with prior PTCA or CABG, valvular or congenital disease, nonischemic cardiomyopathy, or significant (> or = 75%) left main disease were excluded. Baseline clinical, laboratory, and catheterization data were collected prospectively in the Duke Cardiovascular Disease Databank. All patients were contacted at 6 months, 1 year, and annually thereafter (follow-up 97% complete). Cardiovascular death was the primary end point. Of this cohort, 2788 patients were treated with PTCA (2626 within 60 days) and 3422 with CABG (3080 within 60 days). Repeat or crossover revascularization procedures were counted as part of the initial treatment strategy. Kaplan-Meier survival curves (both unadjusted and adjusted for all known imbalances in baseline prognostic factors) were used to examine absolute survival differences, and treatment pair hazard ratios from the Cox model were used to summarize average relative survival benefits. For the latter, a 13-level CAD prognostic index was used to examine the relation between survival and revascularization as a function of CAD severity. The effects of revascularization on survival depended on the extent of CAD. For the least severe forms of CAD (ie, one-vessel disease), there were no survival advantages out to 5 years for revascularization over medical therapy. For intermediate levels of CAD (ie, two-vessel disease), revascularization was associated with higher survival rates than medical therapy. For less severe forms of two-vessel disease, PTCA had a small advantage over CABG, whereas for the most severe form of two-vessel disease (with a critical lesion of the proximal left anterior descending artery), CABG was superior. For the most severe forms of CAD (ie, three-vessel disease), CABG provided a consistent survival advantage over medicine. PTCA appeared prognostically equivalent to medicine in these patients, but the number of PTCA patients in this subgroup was low. CONCLUSIONS In this first large-scale, prospective observational treatment comparison of PTCA, CABG, and medicine, we confirmed the previously reported survival advantages for CABG over medical therapy for three-vessel disease and severe two-vessel disease. For less severe CAD, the primary treatment choices are between medicine and PTCA. In these patients, there is a trend for a relative survival advantage with PTCA, although absolute survival differences were modest. In this setting, treatment decisions should be based not only on survival differences but also on symptom relief, quality of life outcomes, and patient preferences.

Restenosis after coronary angioplasty: An overview☆

Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials. The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials. In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent. In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.

Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction--phase 5 randomized trial. TAMI Study Group.

BackgroundThe efficacy of aspirin for prevention of thrombotic graft occlusion after coronary artery bypass grafting (CABG) depends both on the dosage and time window of administration. Early and late graft patency were therefore assessed in a prospective, double-blind, randomized, placebo-controlled trial of aspirin, 324 mg daily, given within 1 hour of CABG. Methods and ResultsAngiographic graft patency was determined at 1 week (231 patients) and 1 year (219 patients) after CABG. The early vein graft occlusion rate was 1.6% on aspirin and 6.2% on placebo (p = 0.004), and late graft occlusion rate was 5.8% on continued aspirin and 11.6% on placebo (p = 0.01). New graft occlusion between 1 week and 1 year was less common in patients on aspirin than on placebo (4.3% versus 7.4%, p = 0.013). The protective effect of aspirin against occlusion persisted in most subgroups of graft type, graft flow, diameter of recipient artery, location of grafted artery, and endarterectomy. Mean chest tube blood loss for the first 24 hours was 571 ml for the aspirin group and 563 ml for the placebo group. Red cell transfusion requirements were 902 ml in the aspirin group and 934 ml in the placebo group (p=NS). The reoperation rate was 4.8% in the aspirin group and 1% in the placebo group (p = 0.1). ConclusionsImmediate postoperative administration of aspirin (324 mg) improves early graft patency and, with continued usage, protects against further occlusion up to 1 year after CABG. Postoperative blood loss was similar in the two groups; however, aspirin was associated with a nonsignificant higher rate of reoperation.

In vivo validation of compensatory enlargement of atherosclerotic coronary arteries

Necropsy examinations and epicardial ultrasound studies have suggested that atherosclerotic coronary arteries undergo compensatory enlargement. This increase in vessel size may be an important mechanism for maintaining myocardial blood flow. It also is of fundamental importance in the angiographic study of coronary disease progression and regression. The purpose of this study was to determine, using intracoronary ultrasound, whether coronary arteries undergo adaptive expansion in vivo. Forty-four consecutive patients were studied (30 men, 14 women; mean age 56 +/- 10 years). Eighty intravascular ultrasound images were analyzed (32 left main, 23 left anterior descending and 25 right coronary arteries). Internal elastic lamina area, a measure of overall vessel size increased as plaque area expanded (r = 0.57, p = 0.0001, SEE = 5.5 mm2). When the left main, left anterior descending and right coronary arteries were examined individually, there continued to be as great or greater positive correlation between internal elastic lamina and plaque area (left anterior descending: r = 0.75, p = 0.0001; right coronary arteries: r = 0.63, p = 0.0007; left main: r = 0.56, p = 0.0009), implying that each of the vessels and all in aggregate underwent adaptive enlargement. When only those vessels with < 30% area stenosis were examined, internal elastic lamina correlated well with plaque area (r = 0.79, and p = 0.0001), and for each 1 mm2 increase in plaque area, internal elastic lamina increased 2.7 mm2. This suggests that arterial enlargement may overcompensate for early atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis

To determine whether coronary patency could be detected early during thrombolytic therapy, commonly used markers of perfusion were recorded in 386 patients with acute myocardial infarction treated with tissue plasminogen activator. Infarct artery angiography 90 minutes after initiation of therapy was used to determine perfusion status. Of patients with complete resolution of ST segment elevation before the angiogram, 96% (95% confidence interval, 79% to 100%) showed perfusion on the angiogram, and among those with partial improvement, 84% (95% confidence interval, 76% to 90%) showed perfusion, but these findings occurred in only 6% and 38% of patients respectively. When complete resolution of chest pain occurred before the angiogram, 84% of patients (95% confidence interval, 75% to 90%) showed perfusion, but this finding occurred in only 29% of patients. Although arrhythmias occurred frequently in the first 90 minutes of therapy, none were associated with a higher patency rate. No other factors predicted coronary patency. A logistic regression model showed 25% of patients with 90% or greater probability of patency, but 56% of patients with no ST segment or symptom resolution had patent arteries.

Outcome of patients sustaining acute ischemic mitral regurgitation during myocardial infarction.

OBJECTIVE To describe outcomes of patients sustaining an acute myocardial infarction complicated by mitral regurgitation managed with contemporary reperfusion therapies. DESIGN Inception cohort case study. Long-term follow-up was obtained in 99% of all patients. SETTING University referral center. PATIENTS A series of 1,480 consecutive patients presenting between April 1986 and March 1989 who had emergency cardiac catheterization within 6 hours of infarction. Fifty patients were found to have moderately severe or severe mitral regurgitation. OUTCOME MEASURES Mortality; follow-up cardiac catheterization in patients with regurgitation. RESULTS Acute ischemic moderately severe to severe (3+ or 4+) mitral regurgitation was associated with a mortality of 24% at 30 days (95% CI, 12% to 36%), 42% at 6 months (CI, 28% to 56%), and 52% at 1 year (CI, 38% to 66%); multivariable analysis identified 3+ or 4+ mitral regurgitation as a possible independent predictor of mortality (P = 0.06). Patients with mitral regurgitation tended to be female, older, and to have cerebrovascular disease, diabetes, and preexisting symptomatic coronary artery disease. A physical examination did not identify 50% of patients with moderately severe to severe regurgitation. Acute reperfusion with thrombolysis or angioplasty did not reliably reverse valvular incompetence. In this observational study, the greatest in-hospital and 1-year mortalities were seen in patients reperfused with emergency balloon angioplasty, whereas patients managed medically or with coronary bypass surgery had lower mortalities. CONCLUSIONS Moderately severe to severe (3+ or 4+) mitral regurgitation complicating acute myocardial infarction portends a grave prognosis. Acute reperfusion does not reduce mortality to levels experienced by patients with lesser degrees of mitral regurgitation nor does it reliably restore valvular competence.

Percutaneous revascularization of chronic coronary occlusions: An overview

Patients with a chronic coronary occlusion often undergo coronary angiography after weeks to months of occlusion. The published reports underestimate the extent of this problem because such patients are often arbitrarily assigned to receive medical therapy or undergo bypass surgery as a result of poor success with percutaneous revascularization and substantial restenosis. Thus, there is controversy about the role of angioplasty in this patient cohort. The goal of this overview was to evaluate the available information about angioplasty in chronic coronary occlusions. The primary indication for attempted recanalization of a chronic coronary occlusion has been symptomatic angina pectoris. Anginal status often improves after successful procedures (70% vs. 31% with a failed procedure); left ventricular function may improve; and subsequent referral for coronary artery bypass graft surgery is uncommon (3% vs. 28% in unsuccessful cases). Successful recanalization is achieved in approximately 65% of attempted procedures. Inability to cross the stenosis with a guide wire is the most common cause of procedural failure. Statistically significant predictors of procedural success include older occlusions (75% < 3 months old vs. 37% > or = 3 months old), absence of any anterograde flow through the occlusion (76% with vs. 58% without), angiographically abrupt-appearing occlusions (50% vs. 77% with tapered occlusions), presence of bridging collateral vessels (23% with vs. 71% without) and lesions > 15 mm. Procedural complications occur at a slightly lower incidence than in angioplasty of high grade subtotal stenoses. Long-term success is limited, and restenosis can be expected in > 50% of the patients. The experience with chronic total occlusions of saphenous vein bypass grafts is small, but there appear to be limited procedural success and significant procedural complications, particularly associated with distal emboli. The role of new pharmacologic agents has yet to be defined and that of new devices has been disappointing so far, but further technologic advances are on the horizon.

Progression of renal artery stenosis in patients undergoing cardiac catheterization

BACKGROUND Renal artery stenosis is potentially correctable by either revascularization surgery or percutaneous methods. However, appropriate use of these techniques has been hampered by a lack of data on the natural history of this disease. This study assesses the prevalence, risk factors for progression, and effect on renal function of angiographically demonstrated renal artery disease in patients undergoing cardiac catheterization. METHODS The severity of renal artery stenosis was quantified in all patients who underwent abdominal aortography as part of a diagnostic cardiac catheterization study at Duke University Medical Center between January 1989 and February 1996. RESULTS There were 14,152 patients in the study (mean age 61+/-12 years, 62% male). Normal renal arteries were identified in 12,543 (88.7%) patients, insignificant disease (<50% stenosis) in 1 or more vessels in 726 patients (5.1 %), and significant stenosis in 883 patients (6.3%). Significant bilateral renal artery stenosis was present in 178 patients (1.3%). By multivariate logistic regression, elevated serum creatinine level, coronary artery disease, peripheral vascular disease, hypertension, cerebrovascular disease, older age, female sex, and family history of coronary artery disease were identified as independent predictors of significant renal arterial disease. Disease progression was assessed in 1189 patients. Mean time between cardiac catheterizations was 2.6+/-1.6 years. Significant disease progression occurred in 133 patients (11.1 %). Independent predictors of disease progression were female sex, age, coronary artery disease at baseline, and time between baseline and follow-up. At follow-up, serum creatinine level was significantly higher in patients who demonstrated > or =75% stenosis in 1 or more vessels (mean creatinine level 141+114 micromol/L compared with those with insignificant disease (mean creatinine level 97+/-44 micromol/L (P= .01). CONCLUSIONS Renal artery disease is frequently progressive in patients who undergo cardiac catheterization for investigation of coronary artery disease. Significant stenotic disease may develop over a short period despite evidence of normal renal arteries at prior catheterization.