Michael L. Stadius

The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial.

Three hundred sixty-eight patients were randomly assigned to receive intravenous streptokinase (IVSK) (n = 191) or standard therapy (n = 177) to determine the efficacy of IVSK in the treatment of acute myocardial infarction. The mean time to treatment was 3.5 hr. At 14 days there were 12 deaths in the treatment group (6.3%) and 17 deaths in the control group (9.6%) (p = .23). Early mortality was related to infarct location. Fourteen day mortality for anterior infarctions was 10.4% for treatment with IVSK and 22.4% for control patients (p = .06) and was similar for IVSK-treated patients with inferior infarctions, 4.0% vs 1.8% (p = .32). For those randomized under 3 hr, 14 day mortality tends to be lower in treated patients, 5.2% vs 11.5% (p = .11). There was significant improvement in long-term survival for patients with anterior infarction; 2 year survival was 81% for IVSK-treated patients and 65% for control patients (p = .05). There was no improvement in survival for patients with inferior myocardial infarction (p = .27). We conclude that patients with anterior myocardial infarction have improved survival when treated within the first 6 hr of symptoms. Patients with inferior infarction do not appear to have improved survival with thrombolytic therapy. Some of this improvement in survival in patients with anterior infarction may be due to a higher frequency of revascularization procedures in the treatment group.

Intravascular Ultrasound Imaging of Angiographically Normal Coronary Arteries: An In Vivo Comparison With Quantitative Angiography

Intravascular ultrasound, a new technique for real-time two-dimensional visualization of arteries and veins, delineates vessel wall morphology and measures luminal dimensions. This imaging method has been validated with in vitro systems and in peripheral vessels, but there are few in vivo coronary artery studies. Twenty cardiac transplant recipients with no angiographic coronary artery disease were scanned with a 30-MHz intravascular ultrasound catheter from the left main coronary ostium to the mid-left anterior descending coronary artery. Simultaneous angiographic measurements were performed at 76 sites. Ultrasound end-diastolic diameters in two perpendicular axes were 3.8 +/- 0.9 and 3.9 +/- 0.6 mm, respectively, and mean diameter derived from an area determined by planimetry was 3.9 +/- 0.9 mm. Angiographic coronary artery diameters measured with a computer-assisted edge detection system perpendicular to the long axis of the vessel and to the long axis of the catheter were 3.4 +/- 0.8 and 3.6 +/- 0.8 mm, respectively. Luminal diameters measured with the two imaging systems correlated closely, with an r value of 0.86 when ultrasound was compared with the angiographic diameter measured perpendicular to the vessel and 0.88 when compared with the angiographic diameter measured perpendicular to the imaging catheter. Eighty-three percent of the ultrasound-measured diameters were above the line of identity when compared with the simultaneous angiographic measurement. The more the imaging catheter deviated from the long axis of the vessel, the greater was the discrepancy between the ultrasound and angiographic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk stratification for 1 year survival based on characteristics identified in the early hours of acute myocardial infarction: the Western Washington Intracoronary Streptokinase Trial

We evaluated the relationship between baseline factors defined at 4.6 +/- 2.1 hr after onset of acute myocardial infarction and 1 year survival in 245 patients entered in the Western Washington Intracoronary Streptokinase Trial. Univariate statistics identified a significant relationship between 10 of these factors and survival. Multivariate analysis identified three factors as being most closely related to survival: (1) left ventricular ejection fraction (LVEF) (p less than .0001), (2) treatment with streptokinase (p = .03), and (3) location of infarction (p = .04). Mathematic models based on this analysis and applied to our patients identified high- and low-risk subgroups for 1 year mortality. Patients receiving standard, not interventional, therapy with anterior infarction and an LVEF of 50% or less and those with inferior infarction and an LVEF of 39% or less comprised the high-risk group. For patients receiving standard therapy, 1 year mortality was 41% in the high-risk group and 4% in the low-risk group. The models illustrated the magnitude of benefit of streptokinase treatment and achievement of complete reperfusion for those at low and high risk. We conclude that LVEF determined in the first hours of acute myocardial infarction is the most important of all baseline factors for prediction of 1 year survival. Mathematic models based on left ventricular function measured as ejection fraction are useful for risk stratification in this setting.

Survival Following Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Anatomic Subsets in Which Coronary Artery Bypass Surgery Improves Survival Compared With Medical Therapy Results From the Bypass Angioplasty Revascularization Investigation (BARI)

OBJECTIVES We sought to compare survival after coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in high-risk anatomic subsets. BACKGROUND Compared with medical therapy, CABG decreases mortality in patients with three-vessel disease and two-vessel disease involving the proximal left anterior descending artery (LAD), particularly if left ventricular (LV) dysfunction is present. How survival after PTCA and CABG compares in these high-risk anatomic subsets is unknown. METHODS In the Bypass Angioplasty Revascularization Investigation (BARI), 1,829 patients with multivessel disease were randomized to an initial strategy of PTCA or CABG between 1988 and 1991. Stents and IIb/IIIa inhibitors were not utilized. Since patients in BARI with diabetes mellitus had greater survival with CABG, separate analyses of patients without diabetes were performed. RESULTS Seven-year survival among patients with three-vessel disease undergoing PTCA and CABG (n = 754) was 79% versus 84% (p = 0.06), respectively, and 85% versus 87% (p = 0.36) when only non-diabetics (n = 592) were analyzed. In patients with three-vessel disease and reduced LV function (ejection fraction <50%), seven-year survival was 70% versus 74% (p = 0.6) in all PTCA and CABG patients (n = 176), and 82% versus 73% (p = 0.29) among non-diabetic patients (n = 124). Seven-year survival was 87% versus 84% (p = 0.9) in all PTCA and CABG patients (including diabetics) with two-vessel disease involving the proximal LAD (n = 352), and 78% versus 71% (p = 0.7) in patients with two-vessel disease involving the proximal LAD with reduced LV function (n = 72). CONCLUSION In high-risk anatomic subsets in which survival is prolonged by CABG versus medical therapy, revascularization by PTCA and CABG yielded equivalent survival over seven years.

Determinants of normal coronary artery dimensions in humans.

BackgroundStudies of normal human coronary dimensions have been performed primarily in postmortem hearts. We evaluated the influence of age, body habitus, and regional myocardial mass on coronary dimensions in living patients with normal coronary vessels. Methods and ResultsArteriographically normal coronary angiograms were analyzed from the following groups of subjects: group 1 (age, 15–34 years) consisted of 30 post-cardiac transplant patients with donor hearts from male subjects aged 15–34 years, group 2 (age, 35–54 years) consisted of 12 post-cardiac transplant patients with donor hearts from male subjects aged 35–54 years and 26 male subjects investigated for atypical chest pain, and group 3 (age, 55–74 years) consisted of 26 male subjects investigated for atypical chest pain. All angiograms were performed after sublingual nitroglycerin. Measurements of the dimensions of the left main, proximal left anterior descending, proximal left circumflex, and proximal right coronary arteries were made using a computer-assisted edge-detection algorithm. The regional myocardial mass supplied by each vessel was derived from echocardiographically derived total left ventricular mass and a semiquantitative angiographic territory scoring system based primarily on the number and length of its terminal nutrient branches. ConclusionsLinear regression analysis showed that coronary vessel cross-sectional area and total coronary cross-sectional area increase with regional myocardial mass and decrease linearly with age. Multivariate regression analysis revealed that regional myocardial mass and age were independent predictors of cross-sectional area for each vessel and for the total coronary cross-sectional area. We speculate that age-related decline in physical activity, in part, may be responsible.

External beam irradiation inhibits neointimal hyperplasia following balloon angioplasty.

Restenosis is a serious problem limiting the long-term efficacy of percutaneous transluminal coronary angioplasty. Neointimal smooth muscle proliferation is the major process underlying restenosis. The objective of this study was to investigate the effects of external irradiation on neointimal hyperplasia following balloon angioplasty. We examined the ability of external X-ray irradiation to inhibit intimal hyperplasia following balloon angioplasty in a non-atherosclerotic rabbit model. Baseline quantitative angiography (day 0) was performed in all rabbits and balloon angioplasty was performed in the right (control) and the left iliac arteries. Five days after balloon angioplasty, the left iliac in each rabbit was irradiated with either 600 cGy (n = 5) or 1200 cGy (n = 5). Twenty-eight days following angioplasty final angiography was performed. All rabbits were sacrificed, and the iliac arteries were fixed for morphometric measurements. Comparison of baseline and final angiographic measurements revealed a significant decrease in average and minimum lumen dimensions for both control and irradiated segments (600 and 1200 cGy) [average: P (baseline vs. final) 0.008 (control), 0.001 (600 cGy); 0.05 (control), 0.007 (1200 cGy)]. Morphometric analysis showed no difference in neointimal cross-sectional area between control (0.29 +/- 0.05 mm2) and 600 cGy irradiated segments (0.32 +/- 0.07 mm2) (P = 0.82). However, there was a statistically significant reduction in neointimal hyperplasia in the 1200 cGy irradiated segments (0.09 +/- 0.02 mm2) compared to control (0.23 +/- 0.06 mm2, P = 0.02). There was no significant difference in medial cross-sectional area between control and irradiated segments (600 and 1200 cGy). We conclude that in this model, external beam X-ray irradiation (1200 cGy) was successful in reducing neointimal proliferation after balloon angioplasty. Whether or not this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.

Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function.

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had significantly better wall motion of noninfarct areas (SD, 0.36 vs. -0.08, p = 0.02). Treatment effects on function of noninfarct regions were most apparent in the subset of patients with multivessel disease. Thus, intravenous streptokinase preserves left ventricular function in patients with acute myocardial infarction. This benefit includes favorable effects on the function of regions remote from the site of infarction.

Nitroglycerin-induced coronary vasodilation in cardiac transplant recipients. Evaluation with in vivo intracoronary ultrasound.

BackgroundCoronary artery vasomotion is altered after cardiac transplantation. The impact of accelerated transplant coronary atherosclerosis and myocardial rejection on vasomotion is not well understood. Intravascular ultrasound is a new imaging method with the ability to study real-time changes in coronary artery dimensions. Methods and ResultsEpicardial coronary artery response to nitroglycerin was studied in 32 cardiac transplant recipients (age, 47±11 years) 3 weeks to 10 years after transplantation with intracoronary ultrasound. Cross-sectional luminal area and diameter were measured at a fixed position in the left anterior descending artery immediately before and every 30 seconds for 5 minutes after 0.4 mg of sublingual nitroglycerin. Cross-sectional area increased from a baseline of 13.1±3.9 mm2 to 15.8±3.9 mm2 at maximal vasodilation; luminal diameter increased from 4.0±0.6 mm to 4.5±0.6 mm. This increase reached statistical significance (p < 0.001) at 1.5 minutes after administration of nitroglycerin; mean maximum increase occurred at 4.5 minutes (24% for cross-sectional area and 11% for luminal diameter). Patients with biopsy-proven mild or moderate concurrent rejection had a significantly blunted vasodilatory response versus the nonrejection group (9% versus 27% for cross-sectional area, p < 0.04), although a vasodilatory effect was still present. Nitroglycerin response was well preserved in patients up to 10 years after transplantation; however, there was a trend toward a decreased response in patients studied immediately after transplantation (21% versus 29%, p = 0.37). Coronary intimal thickness, as measured by ultrasound, had no impact on the vasodilatory response (R = 0.23, p = 0.34) ConclusionsVasodilatory response to nitroglycerin in cardiac transplant recipients is attenuated during episodes of cardiac rejection. This response is preserved in long-term survivors and is independent of the degree of intimal thickening. Intravascular ultrasound provides a new method to document real-time epicardial coronary vasomotion.

Time course and cellular characteristics of the iliac artery response to acute balloon injury. An angiographic, morphometric, and immunocytochemical analysis in the cholesterol-fed New Zealand white rabbit.

Evaluation of the response of the arterial vessel wall to acute arterial injury in experimental models has taken on substantial importance because of an increasing interest in angioplasty treatment of human atherosclerotic lesions. In this study, the response of normal arterial vessels to acute balloon injury was studied in 45 iliac artery segments from 24 New Zealand White rabbits fed a 2% cholesterol diet. At specified time points between 1 and 41 days after the initial balloon pullback injury, the iliac arteries were analyzed by angiographic, morphometric, and immunocytochemical techniques. Angiographic measurements indicated progressive compromise of the iliac artery lumen with increasing duration of time from injury. Morphometric measurements showed that intimal area increased from 0.004 +/- 0.01 mm2 3 days after injury to 1.15 +/- 0.30 mm2 34-41 days after injury. Cell line-specific immunocytochemical analysis identified the macrophage as a prominent component of the earliest intimal cellular infiltrate. Smooth muscle cells appeared within the intima 7-9 days after injury. As the intima increased in area, macrophages predominated along the internal elastic lamina aspect of the intimal lesion while smooth muscle cells occupied the portion of the intima adjacent to the lumen. In summary, retrograde balloon pullback injury followed by cholesterol feeding results in progressive arterial luminal narrowing due to a progressively enlarging intimal cellular infiltrate. The temporal and spatial contributions of smooth muscle cell and macrophage components of the developing intimal cellular infiltrate have been characterized.

Left ventricular volume determination using single-photon emission computed tomography

A new method for measuring left ventricular (LV) volume based on gated single-photon emission computed tomography (SPECT) is described. Preliminary phantom studies showed an excellent correlation between SPECT and observed volumes (r = 0.99, standard error of the estimate [SEE] = 4.9 ml). SPECT was performed 24 hours after biplane contrast LV angiography in 36 patients. Transaxial blood pool tomograms were reconstructed by filtered back projection and reoriented to views orthogonal to the cardiac axes. Volume was calculated from serial short-axis tomograms by determining the base, apex and lateral borders of the LV blood pool, ascertaining the number of pixels in this volume and multiplying by the known volume of a pixel. Gated SPECT volumes were compared with contrast angiographic volumes. At end-systole, r = 0.96 and SEE = 12 ml; at end-diastole, r = 0.81 and SEE = 27 ml. For ejection fraction, r = 0.85 and SEE = 0.06. To test interobserver variation in processing, count data from 5 patients were processed twice (r = 0.98, SEE = 8.3 ml). There is an excellent correlation between SPECT and contrast angiographic volumes at end-systole; at end-diastole the relation is good. SPECT requires no arbitrary background correction, allows systematic isolation of the left ventricle from other overlapping cardiac chambers and requires no geometric assumptions for volume determination. It has promise as a direct method for measuring LV volume in a minimally invasive manner.