Ronald E. Vlietstra

Restenosis and the proportional neointimal response to coronary artery injury: Results in a porcine model☆

Restenosis is a reparative response to arterial injury occurring with percutaneous coronary revascularization. However, the quantitative characteristics of the relation between vessel injury and the magnitude of restenotic response remain unknown. This study was thus performed to determine the relation between severity of vessel wall injury and the thickness of resulting neointimal proliferation in a porcine model of coronary restenosis. Twenty-six porcine coronary artery segments in 24 pigs were subjected to deep arterial injury with use of overexpanded, percutaneously delivered tantalum wire coils. The vessels were studied microscopically 4 weeks after coil implantation to measure the relation between the extent of injury and the resulting neointimal thickness. For each wire site, a histopathologic score proportional to injury depth and the neointimal thicknesses at that site were determined. Mean injury scores were compared with both mean neointimal thickness and planimetry-derived area percent lumen stenosis. The severity of vessel injury strongly correlated with neointimal thickness and percent diameter stenosis (p less than 0.001). Neointimal proliferation resulting from a given wire was related to injury severity in adjacent wires, suggesting an interaction among effects at injured sites. If the results in this model apply to human coronary arteries, restenosis may depend on the degree of vessel injury sustained during angioplasty.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA): A report from the PTCA registry of the national heart, lung, and blood institute

The results of follow-up angiography in patients from 27 clinical centers enrolled in the PTCA Registry were analyzed to evaluate restenosis after PTCA. Of 665 patients with successful PTCA, 557 (84%) had follow-up angiography (median follow-up 188 days). Restenosis, defined as an increase of at least 30% from the immediate post-PTCA stenosis to the follow-up stenosis or a loss of at least 50% of the gain achieved at PTCA, was seen in 187 patients (33.6%). The incidence of restenosis in patients who underwent follow-up angiography was highest within the first 5 months after PTCA. Restenosis was found in 56% of patients with definite or probable angina after PTCA and in 14% of patients without angina after PTCA. Twenty-four percent of patients with restenosis did not have either definite or probable angina. Multivariate analysis selected 4 factors associated with increased rate of restenosis: male sex, PTCA of bypass graft stenosis, severity of angina before PTCA and no history of MI before PTCA.

A Platelet-Inhibitor-Drug Trial in Coronary-Artery Bypass Operations: Benefit of Perioperative Dipyridamole and Aspirin Therapy on Early Postoperative Vein-Graft Patency

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.

Continuous-wave Doppler echocardiographic assessment of severity of calcific aortic stenosis: a simultaneous Doppler-catheter correlative study in 100 adult patients.

Studies of the correlation of aortic valve gradient determined by continuous-wave Doppler echocardiography and that determined at catheterization have, to date, involved young patients and nonsimultaneous measurements. We therefore obtained simultaneous Doppler echocardiographic and catheter measurements of pressure gradient in 100 consecutive adults (mean age 69, range 50 to 89 years). In 63 patients pressure measurements were obtained with dual-catheter techniques and in 37 they were obtained by withdrawal of the catheter from the left ventricle to the ascending aorta. Forty-six of these patients also underwent an outpatient Doppler study 7 days or less before catheterization. The simultaneous pressure waveforms and Doppler spectral velocity profiles were digitized at 10 msec intervals and maximum, mean, and instantaneous gradients (mm Hg) were derived for each. The correlation between the Doppler-determined gradient and the simultaneously measured maximum catheter gradient was r = .92 (SEE = 15 mm Hg), that between the Doppler-determined and mean catheter gradient was r = .93 (SEE = 10 mm Hg), and that between the Doppler and peak-to-peak catheter gradient was r = .91 (SEE = 14). The correlation between the nonsimultaneously Doppler-determined gradient and the maximum gradient measured by catheter was not as strong (r = .79, SEE = 24). The continuous-wave Doppler echocardiographic velocity profile represents the instantaneous transaortic pressure gradient throughout the cardiac cycle. The best correlation with continuous-wave Doppler-determined gradient was obtained with maximum and mean gradients measured by catheter. Continuous-wave Doppler echocardiography can be used to reliably predict the pressure gradient in adults with calcific aortic stenosis.

Seven year survival of patients with normal or near normal coronary arteriograms: A CASS registry study

The effect on 7 year survival of having a normal or near normal coronary arteriogram was examined using data from the CASS registry of 21,487 consecutive coronary arteriograms taken in 15 clinical sites. Of these, 4,051 arteriograms were normal or near normal, and the patients had normal left ventricular function as judged by absence of a history of congestive heart failure, no reported segmental wall motion abnormality and an ejection fraction of at least 50%; 3,136 arteriograms were entirely normal and the remaining 915 revealed mild disease with less than 50% stenosis in one or more segments. The 7 year survival rate was 96% for the patients with a normal arteriogram and 92% for those whose study revealed mild disease (p less than 0.0001). Nine risk variables recorded at entry were analyzed for predictive value for survival: age, sex, height, weight, history of smoking, presence of absence of mild disease, electrocardiographic response to exercise, family history of coronary heart disease and a history of hypertension. Of these, age, smoking history, presence or absence of disease and a history of hypertension had predictive value.

Predictors of in-hospital and 6-month outcome after acute myocardial infarction in the reperfusion era: The primary angioplasty in myocardial infarction (PAMI) trial

OBJECTIVES This study examined the predictors of in-hospital and 6-month outcome after different reperfusion strategies in acute myocardial infarction. BACKGROUND Thrombolytic therapy and primary angioplasty are both widely applied as reperfusion modalities in patients with myocardial infarction. Although it is accepted that restoration of early patency of the infarct-related artery can reduce mortality and salvage myocardium, the optimal reperfusion strategy remains controversial, and the predictors of outcome in the reperfusion era have been incompletely characterized. METHODS At 12 centers, 395 patients presenting within 12 h of onset of acute transmural myocardial infarction were prospectively randomized to receive tissue-type plasminogen activator (t-PA) or undergo primary angioplasty without antecedent thrombolysis. Sixteen clinical variables were examined with univariate and multiple logistic regression analysis to identify the predictors of clinical outcome. RESULTS By univariate analysis, in-hospital mortality was increased in the elderly, women, patients with diabetes and in patients treated with t-PA as opposed to angioplasty. Only advanced age and treatment by t-PA versus angioplasty independently correlated with increased in-hospital mortality (6.5% vs. 2.6%, respectively, p = 0.039 by multiple logistic regression analysis). Similarly, the only variables independently related to in-hospital death or nonfatal reinfarction were advanced age and treatment by t-PA versus angioplasty (12.0% vs. 5.1%, p = 0.02). The reduction in in-hospital death or reinfarction with angioplasty versus t-PA was particularly marked in patients > or = 65 years of age (8.6% vs. 20.0%, p = 0.048). Furthermore, primary management with angioplasty versus t-PA was the most powerful multivariate correlate of freedom from recurrent ischemic events (10.3% vs. 28.0%, p = 0.0001). The independent beneficial effect of angioplasty on freedom from death or reinfarction was maintained at 6-month follow-up (8.2% vs. 17.0%, p = 0.02). CONCLUSIONS In the reperfusion era, the two most powerful determinants of freedom from death, reinfarction and recurrent ischemia after myocardial infarction are young age and treatment by primary angioplasty.

Intracoronary thrombus: Role in coronary occlusion complicating percutaneous transluminal coronary angioplasty

Angiograms from 238 consecutive patients who underwent percutaneous transluminal coronary angioplasty at the Mayo Clinic were reviewed to determine the presence of intracoronary thrombus before dilation. Patients with previously occluded vessels and those receiving streptokinase therapy were excluded. Intracoronary thrombus before dilation was present in 15 patients (6%); complete occlusion occurred in 11 (73%) of these during or immediately after dilation. None of these patients had angiographic evidence of major intimal dissection. In contrast, among the 223 patients in whom no intracoronary thrombus was present before dilation, complete occlusion occurred in 18 (8%) and in 12 was associated with major intimal dissection. The difference between the complete occlusion rates for patients with and without prior intracoronary thrombus was highly significant (73 versus 8%, respectively, p less than 0.001). Therefore, the presence of intracoronary thrombus identifies a group of patients who are at increased risk of developing complete occlusion during or after attempted coronary artery dilation.

Comparison of complications during percutaneous transluminal coronary angioplasty from 1977 to 1981 and from 1985 to 1986: The National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry

Because the effects of changing technology in percutaneous transluminal coronary angioplasty, increased operator experience and use of the procedure in patients with extensive disease are unknown in regard to complication patterns, the initial 1977-1981 cohort and the recent 1985-1986 cohort of the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry were analyzed with respect to complications. Compared with the initial cohort of 1,155 patients, the 1,801 new cohort patients were older and had an increased prevalence of multivessel coronary artery disease, depressed left ventricular function and prior infarction. Overall complication rates in the recent cohort were either unchanged or decreased from the rates in the initial cohort despite a higher risk patient population. The most significant decreases were in the incidence of coronary spasm (p less than 0.001) and the need for emergency coronary bypass surgery (p less than 0.01). Overall in-hospital mortality was low but was dependent on the extent of vessel disease--0.2% for single vessel disease, 0.9% for double vessel disease and 2.2% for triple vessel disease (p less than 0.001 for linear trend). Acute coronary complications of branch occlusion, dissection or abrupt closure were associated with increased rates of death, nonfatal infarction or need for emergency surgery. Factors showing a multivariate association with increased mortality included a history of congestive heart failure (p less than 0.001), age greater than or equal to 65 years (p less than 0.01), triple vessel or left main coronary artery disease (p less than 0.05), female gender (p less than 0.05) and new onset angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Risks for Renal Dysfunction with Cardiac Angiography

In 139 patients with preexisting abnormal renal function (serum creatinine level of 2.0 mg/dL or greater) undergoing cardiac angiography (141 examinations), the incidence of contrast nephropathy, defined as a 1 mg/dL or greater rise in serum creatinine, was 23% (95% confidence interval, 17% to 30%). Stepwise logistic regression analysis showed that contrast nephropathy was independently associated with class IV heart failure with low cardiac output (71% incidence in this subgroup; p less than 0.0001), multiple radiocontrast studies within 72 hours (50%; p = 0.002), dose of radiocontrast administered (p = 0.009), and insulin-dependent diabetes mellitus (44%; p = 0.007). Age, hypertension, and hyperuricemia were not associated. In patients without low cardiac output, other radiocontrast tests, or insulin-dependent diabetes mellitus, there was a 2% incidence of contrast nephropathy in those who received less than 125 mL radiocontrast and a 19% incidence in those who received 125 mL or greater.

Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury

Human coronary artery restenosis after percutaneous revascularization is a response to mechanical injury. Smooth muscle cell proliferation is a major component of restenosis, resulting in obstructive neointimal hyperplasia. Because ionizing radiation inhibits cellular proliferation, this study tested in a porcine coronary injury model the hypothesis that the hyperplastic response to coronary artery injury would be attenuated by X-irradiation. Deep arterial injury was produced in 37 porcine left anterior descending coronary artery segments with overexpanded, percutaneously delivered tantalum wire coils. Three groups of pigs were irradiated with 300-kV X-rays after coil injury: Group I (n = 10), 400 cGy at 1 day; Group II (n = 10), 400 cGy at 1 day and 400 cGy at 4 days and Group III (n = 9), 800 cGy at 1 day. Eight pigs in the control group underwent identical injury but received no radiation. Treatment efficacy was histologically assessed by measuring neointimal thickness and percent area stenosis. Mean neointimal thickness in all irradiated groups was significantly higher than in the control groups and thickness was proportional to X-ray dose. X-irradiation delivered at these doses and times did not inhibit proliferative neointima. Rather, it accentuated the neointimal response to acute arterial injury and may have potentiated that injury.