Robert S. Gibson

Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography.

The ability of predischarge quantitative exercise thallium-201 (201T1) scintigraphy to predict future cardiac events was evaluated prospectively in 140 consecutive patients with uncomplicated acute myocardial infarction; the results were compared with those of submaximal exercise treadmill testing and coronary angiography. High risk was assigned if scintigraphy detected 201T1 defects in more than one discrete vascular region, redistribution, or increased lung uptake, if exercise testing caused ST segment depression greater than or equal to 1 mm or angina or if angiography revealed multivessel disease. Low risk was designated if scintigraphy detected a single-region defect, no redistribution, or no increase in lung uptake, if exercise testing caused no ST segment depression or angina, or if angiography revealed single-vessel disease or no disease. By 15 +/- 12 months, 50 patients had experienced a cardiac event; seven died (five suddenly), nine suffered recurrent myocardial infarction, and 34 developed severe class III or IV angina pectoris. Compared with that of patients at low risk, the cumulative probability of a cardiac event was greater in high-risk patients identified by scintigraphy (p less than .001), exercise testing (p = .011), or angiography (p = .007). Scintigraphy predicted low-risk status better than exercise testing (p = .01) or angiography (p = .05). Each predicted mortality with equal accuracy. However, scintigraphy was more sensitive in detecting patients who experienced reinfarction or who developed class III or IV angina. When all 50 patients with events were combined, scintigraphy identified 47 high-risk patients (94%), whereas exercise-induced ST segment depression or angina detected only 28 (56%) (p less than .001). The presence of multivessel disease as assessed by angiography identified nine more patients with events than exercise testing (p = .06). However, the overall sensitivity of angiography was lower than that of scintigraphy (71% vs 94%; p less than .01) because three patients who experienced reinfarction and 10 who developed class III or IV angina had single-vessel disease. Importantly, 12 (92%) of these 13 patients with single-vessel disease who had an event exhibited redistribution on scintigraphy. These results indicate that (1) submaximal exercise 201T1 scintigraphy can distinguish high- and low-risk groups after uncomplicated acute myocardial infarction before hospital discharge; (2) 201T1 defects in more than one discrete vascular region, presence of delayed redistribution, or increased lung thallium uptake are more sensitive predictors of subsequent cardiac events than ST segment depression, angina, or extent of angiographic disease; and (3) low-risk patients are best identified by a single-region 201T1 defect without redistribution and no increased lung uptake.

Diltiazem and Reinfarction in Patients with Non-Q-Wave Myocardial Infarction

We performed a multicenter, double-blind, randomized study to evaluate the effect of diltiazem on reinfarction after a non-Q-wave myocardial infarction. Nine centers enrolled 576 patients: 287 received diltiazem (90 mg every six hours) and 289 received placebo. Treatment was initiated 24 to 72 hours after the onset of infarction and continued for up to 14 days. The primary end point, reinfarction, was defined as an abnormal reelevation of MB creatine kinase in plasma within 14 days. Reinfarction occurred in 27 patients in the placebo group (9.3 percent) and in 15 in the diltiazem group (5.2 percent)--a 51.2 percent reduction in cumulative life-table incidence (P = 0.0297; 90 percent confidence interval, 7 to 67 percent). Diltiazem reduced the frequency of refractory postinfarction angina (a secondary end point) by 49.7 percent (P = 0.0345; 90 percent confidence interval, 6 to 73 percent). Mortality was similar in the two groups (3.1 and 3.8 percent, respectively, in the placebo and diltiazem groups), but adverse drug reactions (most of which were mild) were more common in the diltiazem group. Nevertheless, the drug was well tolerated, despite concurrent treatment with beta-blockers in 61 percent of the patients. We conclude that diltiazem was effective in preventing early reinfarction and severe angina after non-Q-wave infarction and that it was also safe and generally well tolerated.

The Electrocardiogram Predicts One-Year Outcome of Patients With Unstable Angina and Non–Q Wave Myocardial Infarction: Results of the TIMI III Registry ECG Ancillary Study

OBJECTIVES We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI). BACKGROUND Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy. METHODS ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI. RESULTS New ST segment deviation > or = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with > or = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either > or = 1 mm or > or = 0.5 mm remained independent predictors of death or MI by 1 year. CONCLUSIONS The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not only > or = 1-mm ST segment deviation but also > or = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

Prospective assessment of regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy.

Because thallium-201 uptake relates directly to the amount of viable myocardium and nutrient blood flow, the potential for exercise scintigraphy to predict response to coronary revascularization surgery was investigated in 47 consecutive patients. All patients underwent thallium-201 scintigraphy and coronary angiography at a mean (+/- standard deviation) of 4.3 +/- 3.1 weeks before and 7.5 +/- 1.6 weeks after surgery. Thallium uptake and washout were computer-quantified and each of six segments was defined as normal, showing total or partial redistribution or a persistent defect. Persistent defects were further classified according to the percent reduction in regional thallium activity; PD25-50 denoted a 25 to 50% constant reduction in relative thallium activity and PD greater than 50 denoted a greater than 50% reduction. Of 82 segments with total redistribution before surgery, 76 (93%) showed normal thallium uptake and washout postoperatively, versus only 16 (73%) of 22 with partial redistribution (probability [p] = 0.01). Preoperative ventriculography revealed that 95% of the segments with total redistribution had preserved wall motion, versus only 74% of those with partial redistribution (p = 0.01). Of 42 persistent defects thought to represent myocardial scar before surgery, 19 (45%) demonstrated normal perfusion postoperatively. Of the persistent defects that showed improved thallium perfusion postoperatively, 75% had normal or hypokinetic wall motion before surgery, versus only 14% of those without improvement (p less than 0.001). Whereas 57% of the persistent defects that showed a 25 to 50% decrease in myocardial activity demonstrated normal thallium uptake and washout postoperatively, only 21% of the persistent defects with a decrease in myocardial activity greater than 50% demonstrated improved perfusion after surgery (p = 0.02). Thus, preoperative quantitative thallium-201 scintigraphy appears useful in predicting response to revascularization surgery, and some persistent defects may revert to normal thallium uptake after surgery. Importantly, the preoperative distinction between viable and nonviable myocardium can be reasonably established by quantitating the amount of persistent reduction in thallium uptake and correlating this with preoperative wall motion.

Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis

A 2-part prospective study was performed to evaluate the clinical outcome of patients with hemodynamically confirmed asymptomatic valvular aortic stenosis (AS). During phase 1, linear regression analysis showed continuous wave Doppler to be highly accurate in predicting catheterization measured peak systolic aortic valve pressure gradients in 101 consecutive patients aged 36 to 83 years (mean 65 +/- 8) with symptomatic AS. During phase 2, 90 additional patients (51 asymptomatic and 39 symptomatic) with Doppler-derived peak systolic aortic valve gradients greater than or equal to 50 mm Hg (range 50 to 132 [mean 68 +/- 19]) were followed for 1 to 45 months. Both groups of patients in phase 2 had similar Doppler gradients and clinical and auscultatory evidence of moderate to severe AS at baseline. Asymptomatic patients were younger (p = 0.01), had higher ejection fractions (p = 0.001) and were less likely to have an electrocardiographic strain pattern (p = 0.01) and left atrial enlargement (p = 0.02). End-diastolic wall thickness, left ventricular cross-sectional myocardial area and estimated left ventricular mass were 18% (p = 0.0001), 20% (p = 0.0008), and 29% (p = 0.002) greater in symptomatic patients. During 17 +/- 9 months of follow-up, 21 asymptomatic patients (41%) became symptomatic. Dyspnea was the most common initial complaint, occurring 2.5 and 4.8 times more often than angina and syncope, respectively. Compared with the 39 symptomatic patients, the 51 asymptomatic patients had a lower cumulative life table incidence of death from any cause (p = 0.002), and from cardiac causes (p = 0.0001) including sudden death (p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)

Value of early two dimensional echocardiography in patients with acute myocardial infarction

Abstract Seventy-five consecutive patients with acute myocardial infarction underwent two dimensional echocardiography 7.9 ±3.1 hours after admission (1) to determine if this procedure can detect regional left ventricular asynergy in an unselected series of patients; (2) to evaluate the relation of asynergy outside the electrocardiographic infarct zone to clinical events and coronary anatomic findings; and (3) to determine whether the procedure can identify patients at high risk for cardiogenic shock, before the onset of hemodynamic deterioration. For purposes of analysis, the left ventricle was divided into 11 segments; individual segments were evaluated for systolic wall motion and thickening, and a wall motion index was calculated as a measure of global left ventricular performance. Technically satisfactory two dimensional echographic studies were obtained in all 75 patients. Of 825 possible segments in the 75 patients, 795 (96 percent) or 10.6 segments per patient were deemed adequate for analysis. Akinesia or dyskinesia was detected in at least one segment in all patients, including 15 (20 percent) who underwent imaging within 4 hours of the onset of symptoms and 19 (25 percent) with nontransmural infarction. Severe wall motion abnormalities outside the infarct zone were observed in 47 percent of patients and correlated with a greater prevalence of death (p = 0.03), cardiogenic shock (p Thus, two dimensional echocardiography performed soon after admission to the coronary care unit is technically feasible, provides useful information concerning regional and global left ventricular function and offers important predictive information about patients early in acute myocardial infarction.

A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) 5 trial

OBJECTIVES The purpose of this study was to assess the value of recombinant desulfatohirudin (hirudin) as adjunctive therapy to thrombolysis in acute myocardial infarction. BACKGROUND Failure to achieve initial reperfusion and reocclusion of the infarct-related artery remain major limitations of thrombolytic therapy despite aggressive regimens of heparin and aspirin. Hirudin, a direct thrombin inhibitor, has been shown in experimental models to enhance thrombolysis and reduce reocclusion. METHODS The Thrombolysis in Myocardial Infarction (TIMI) 5 trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin, given with front-loaded tissue-type plasminogen activator and aspirin to 246 patients with acute myocardial infarction. Patients received either intravenous heparin or hirudin at one of four ascending doses for 5 days. Patients underwent coronary angiography at 90 min and at 18 to 36 h, unless rescue angioplasty was performed. RESULTS The primary end point, TIMI grade 3 flow in the infarct-related artery at 90 min and 18 to 36 h without death or reinfarction before the 18- to 36-h catheterization was achieved in 97 (61.8%) of 157 evaluable hirudin-treated patients compared with 39 (49.4%) of 79 evaluable heparin-treated patients (p = 0.07). All four doses of hirudin led to similar findings in the angiographic and clinical end points. At 90 min, TIMI grade 3 flow was present in 105 (64.8%) of 162 hirudin-treated patients compared with 48 (57.1%) of 84 heparin-treated patients (p = NS). Infarct-related artery patency (TIMI grade 2 or 3 flow) was similar in the two groups (82.1% and 78.6%, respectively). At 18 to 36 h, 129 (97.8%) of 132 hirudin-treated patients had a patent infarct-related artery compared with 58 (89.2%) of 65 heparin-treated patients (p = 0.01). Reocclusion by 18 to 36 h occurred in 2 (1.6%) of 123 hirudin-treated patients versus 4 (6.7%) of 60 heparin-treated patients (p = 0.07). Death or reinfarction occurred during the hospital period in 11 (6.8%) of 162 hirudin-treated patients compared with 14 (16.7%) of 84 heparin-treated patients (p = 0.02). Major spontaneous hemorrhage occurred in 1.2% of hirudin-treated patients versus 4.7% of heparin-treated patients (p = 0.09), and major hemorrhage at an instrumented site occurred in 16.3% and 18.6%, respectively (p = NS). CONCLUSIONS Hirudin is a promising agent compared with heparin as adjunctive therapy with thrombolysis for acute myocardial infarction, and its evaluation in larger trials is warranted.

The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: a prospective natural history study.

Despite having smaller infarct size and better left ventricular function, patients with non-Q wave myocardial infarction (NQMI) appear to have an unexpectedly high long-term mortality that is ultimately comparable to that of patients with Q-wave myocardial infarction (QMI). Patients with NQMI may lose their initial prognostic advantage because there is more viable tissue in the perfusion zone of the infarct-related vessel, rendering myocardium more prone to reinfarction. We tested this hypothesis in a prospective study of 241 consecutive patients 65 years of age or younger with acute uncomplicated myocardial infarction confirmed by creatine kinase levels (MB fraction). All patients received customary care and none underwent thrombolytic therapy or emergency angioplasty. Predischarge coronary angiography, radionuclide ventriculography, 24 hr Holter monitoring, and quantitative thallium-201 (201T1) scintigraphy during treadmill exercise were performed 10 +/- 3 days after infarction. Infarcts were designated as QMI (n = 154) or NQMI (n = 87) by accepted criteria applied to serial electrocardiograms obtained on days 1, 2, 3, and 10. The baseline Norris coronary prognostic index, angiographic jeopardy scores, and prevalence of Lown grade ventricular arrhythmias were similar between groups despite evidence for less necrosis with NQMI vs QMI, reflected by lower peak creatine kinase levels (520 vs 1334 IU/liter; p = .0001, 4 hr sampling), higher resting left ventricular ejection fraction (53% vs 46%; p = .0001), fewer akinetic or dyskinetic segments (1.2 vs 2.4; p = .0001), and fewer persistent 201Tl defects in the infarct zone (0.9 vs 1.9; p = .0001). Patients with NQMI also had more patent infarct-related vessels (54% vs 25%; p less than .0001) and a shorter time from onset of infarction to peak creatine kinase level (16.9 vs 22.5 hr; p = .0001). Importantly, the prevalence and extent of quantitatively determined 201Tl redistribution within the infarct zone on exercise scintigraphy was greater in patients with NQMI vs those with QMI (60% vs 36%, p = .007; and 0.98 vs 0.53 myocardial segments, p = .0003); when the two groups were stratified on the basis of the infarct-related vessel, subset analysis revealed the same findings. During 30 months median follow-up, cardiac mortality was low, 8.4% in the QMI group and 9.2% in the NQMI group (p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Postinfarction ventricular septal rupture: the importance of location of infarction and right ventricular function in determining survival.

Over a 5.5 year period, 1264 consecutive patients with acute myocardial infarction as confirmed by enzyme levels were prospectively identified. Of these, 25 (2%) suffered ventricular septal rupture (pulmonary/systemic flow range 1.5 to 6) 7 +/- 7 days after onset of myocardial infarction. Death occurred in 14 patients (56%) and was more common after inferior than anterior myocardial infarction (11 of 15 [73%] vs three of 10 [30%], p less than .05). Among 133 variables analyzed, survivors and nonsurvivors were similar with respect to all premorbid clinical characteristics, infarct size as assessed by peak creatine kinase values, shunt size, two-dimensional echocardiographic and hemodynamic indexes of left ventricular function, and extent of coronary disease. Compared with survivors, the nonsurvivors had greater impairment of right ventricular function as determined by a higher two-dimensional echocardiographically derived right ventricular wall motion index (RVWMI) (0.55 +/- 0.87 vs 1.70 +/- 0.45, p less than .001), greater elevation of right ventricular end-diastolic pressure (11 +/- 6 vs 17 +/- 6, p less than .02), and greater mean right atrial pressure (10 +/- 6 vs 16 +/- 3, p less than .01). Of interest, two of the three patients who presented with anterior myocardial infarction and who died had inferiorly extended infarcts and all had abnormal RVWMIs (greater than or equal to 1.0). As expected, cardiogenic shock shortly after onset of ventricular septal rupture was associated with a 91% mortality, but was more common after inferior than anterior myocardial infarction (60% vs 20%, p less than .05). The mean effective cardiac index was also higher in survivors than nonsurvivors (2.1 +/- 0.5 vs 1.2 +/- 0.5, p less than .001). Finally, multivariate analysis indicated that all nonsurvivors could be identified based on: an effective cardiac index of 1.75 liters/min/m2 or less, the presence of extensive right ventricular and septal dysfunction on the two-dimensional echocardiogram, a mean right atrial pressure of 12 mm Hg or more, and early onset of ventricular septal rupture. Thus, our data demonstrate that: mortality is higher when ventricular septal rupture complicates inferior than when it complicates anterior myocardial infarction, survivors can be distinguished from nonsurvivors and the prediction of outcome is highly accurate, and combined right ventricular and septal dysfunction has a substantial impact on prognosis.

Prognostic utility of the exercise thallium-201 test in ambulatory patients with chest pain: comparison with cardiac catheterization.

The goal of this study was to determine the prognostic utility of the exercise thallium-201 stress test in ambulatory patients with chest pain who were also referred for cardiac catheterization. Accordingly, 4 to 8 year (mean +/- 1SD, 4.6 +/- 2.6 years) follow-up data were obtained for all but one of 383 patients who underwent both exercise thallium-201 stress testing and cardiac catheterization from 1978 to 1981. Eighty-three patients had a revascularization procedure performed within 3 months of testing and were excluded from analysis. Of the remaining 299 patients, 210 had no events and 89 had events (41 deaths, nine nonfatal myocardial infarctions, and 39 revascularization procedures greater than or equal to 3 months after testing). When all clinical, exercise, thallium-201, and catheterization variables were analyzed by Cox regression analysis, the number of diseased vessels (when defined as greater than or equal to 50% luminal diameter narrowing) was the single most important predictor of future cardiac events (chi 2 = 38.1) followed by the number of segments demonstrating redistribution on delayed thallium-201 images (chi 2 = 16.3), except in the case of nonfatal myocardial infarction, for which redistribution was the most important predictor of future events. When coronary artery disease was defined as 70% or greater luminal diameter narrowing, the number of diseased vessels significantly (p less than .01) lost its power to predict events (chi 2 = 14.5). Other variables found to independently predict future events included change in heart rate from rest to exercise (chi 2 = 13.0), ST segment depression on exercise (chi 2 = 13.0), occurrence of ventricular arrhythmias on exercise (chi 2 = 5.9), and beta-blocker therapy (chi 2 = 4.3). The exclusion of myocardial revascularization procedures as an event did not change the results significantly. Although the number of diseased vessels was the single most important determinant of future events, the exercise thallium-201 stress test when considered as a whole (which included the number of segments demonstrating redistribution on delayed thallium-201 images, change in heart rate from rest to exercise, ST segment depression on the electrocardiogram, and ventricular premature beats on exercise) was equally powerful (chi 2 = 41.6). Combination of both catheterization and exercise thallium-201 data was superior to either alone (chi 2 = 57.5) for determining future events. Exercise stress test alone (without thallium-201 data) was inferior to the exercise thallium-201 stress test or cardiac catheterization for predicting future events (chi 2 = 30.6).(ABSTRACT TRUNCATED AT 400 WORDS)