Emeritus Faculty, Acad Council, Medicine - Cardiovascular Medicine
Clinical coronary artery disease:
Outcome of coronary revascularization procedures compared to medical treatment. Comparison of coronary surgery with percutaneous coronary angioplasty (PTCA) for treatment of multi-vessel disease.
Angiographic assessment of coronary disease severity and angiographic predictors of disease progression and of clinical events.
Angiographic trials of anti-atherosclerotic interventions:
Randomized clinical trials of behavioral and pharmacologic interventions for inhibiting progression or causing regression of coronary atheroma. Use of computer assisted angiographic quantitation for measurement of small changes in dimensions of coronary vessels in serial studies. Use of intra-coronary ultrasonic imaging for quantitation of changes in the thickness and characteristics of coronary atheromas.
Coronary artery disease in cardiac transplant recipients:
Cardiac transplant recipients develop an aggressive form of atherosclerosis with progression substantially more rapid than in non-transplant patients with coronary disease. Using coronary quantitation and intra-coronary ultrasound, it is possible to assess the efficacy of different drugs in randomized studies.
Studies of cardiac hemodynamics in patients with coronary, valvular and cardiomyopathic disease. Effect of physiologic and drug interventions in patients with heart failure, angina or asymptomatic LV dysfunction.
The Bypass Angioplasty Revascularization Investigation (BARI) randomized 1,829 patients to percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Clinical site angiographers categorized lesions of > or = 50% diameter stenosis (n = 4,977) as clinically significant (86.4%) or nonsignificant (13.6%), and as favorable or nonfavorable for PTCA or CABG. More lesions were considered favorable for revascularization by CABG than by PTCA (91.5% vs 78.4%; p <0.001), particularly in the subgroup of 99% to 100% lesions (77.6% for CABG vs 21.9% for PTCA, p <0.001). Lesion features, characterized by the BARI core laboratory, were correlated with clinical site angiographers' assessment of clinical importance and suitability for PTCA or CABG. By multivariate analysis, positive predictors of clinical importance for 50% to 95% stenoses were greater stenosis severity, more jeopardized myocardium, larger reference diameter, and proximal vessel location. For 99% to 100% occlusions, predictors were shorter duration of occlusion and more jeopardized myocardium. PTCA suitability for 50% to 95% stenoses was inversely related to lesion length, ostial location, location on a bend, difficult access, and age, and was directly associated with greater Thrombolysis in Myocardial Infarction (TIMI) trial flow rate and more jeopardized myocardium. Predictors of PTCA suitability for 99% to 100% lesions were a lower American College of Cardiology/American Heart Association class and higher TIMI grade. Predictors for 50% to 95% stenoses were more jeopardized myocardium, larger reference diameter, and more proximal vessel location, and for 99% to 100% occlusions, more jeopardized myocardium and shorter duration of occlusion. Suitability for PTCA depended on lesion potency (<99%) and multiple morphologic characteristics that contrasted with the few angiographic features that adversely affect CABG suitability.
View details for Web of Science ID A1996UJ93800003
View details for PubMedID 8623731
Although intracoronary ultrasound (ICUS) has been validated for the early detection of transplant coronary artery disease (TxCAD), the prognostic importance of findings detected by this new imaging technique is unknown.This study examined the relation of clinical outcome in 145 heart transplant recipients (mean age, 45.1 +/- 11.1 years) with the amount of intimal thickness measured by ICUS during routine annual coronary angiography 1 to 10 years (mean, 3.1 +/- 2.2 years) after transplantation. From published autopsy data, a mean intimal thickness of > 0.3 mm was considered significant. During a mean follow-up time of 48.2 +/- 10.2 months, 23 deaths (12 cardiac) occurred, and 6 patients required retransplantation. Angiographic TxCAD developed in 22 of 125 patients (17.6%) in the subgroup with normal angiograms at the time of ICUS and a follow-up annual angiographic study. In the total population and the subgroup, mean intimal thicknesses of > 0.3 and < or = 0.3 mm, respectively, were associated with significantly inferior 4-year actuarial overall survival (73% versus 96%, P = .005; 72% versus 92%, P = .05), cardiac survival (79% versus 96%, P = .005; 80% versus 98%, P = .04), and freedom from cardiac death and retransplantation (74% versus 98%, P < .0001; 70% versus 96%, P = .001). In addition, ICUS predicted freedom from development of subsequent angiographic TxCAD in the subgroup that was initially normal (26% versus 72%, P = .02). A mean intimal thickness by ICUS of > 0.3 mm was associated with inferior clinical outcome regardless of the presence of angiographic TxCAD and predicted the development of subsequent angiographic TxCAD. Despite significantly longer duration after transplantation, higher rejection incidence, and lower average daily cyclosporine dose, none of these covariates were independent risk factors for outcome.These findings confirm the prognostic importance of mean intimal thickening of > 0.3 mm in heart transplant recipients and suggest that these patients should be candidates for early interventional strategies.
View details for Web of Science ID A1995TJ65500018
View details for PubMedID 8521566
The mechanisms responsible for transplant coronary artery disease (CAD) and its predisposing factors remain incompletely understood. The influence of donor characteristics as predisposing factors has not been studied systematically. We examined the correlation of donor demographic, clinical, and immunologic parameters with transplant CAD assessed by both intracoronary ultrasound (ICUS) and coronary angiography in 116 heart transplant recipients (age 44.7 +/- 12.0 years) studied 3.4 years (range 1.0 to 14.6) after transplantation. Quantitative ultrasound data were obtained by calculating mean intimal thickness from several distinct coronary sites. Coronary angiograms were categorized visually as normal or showing any transplant CAD. By multivariate regression analysis, donor undersize of > 20% of recipient weight (p < 0.02) and duration after transplantation (p < 0.005) were independently correlated with the amount of ICUS intimal thickness (r = 0.36, p = 0.0007), and older donor age with angiographic evidence for the disease (r = 0.34, p < 0.006). In a subgroup analysis of the 39 patients studied 1 year after transplantation, white donor race (p < 0.05), fewer human leukocyte antigen-DR mismatches (p < 0.002), shorter ischemic time (p < 0.04), and donor smoking history (p < 0.02) were independent predictors for severity of ICUS intimal thickening (r = 0.92, p = 0.0009); higher donor age (p < 0.006) and higher arterial partial pressure of oxygen (p < 0.003) were independent predictors for angiographic disease (r = 0.67, p < 0.002). In conclusion, donor characteristics may contribute to the probably multifactorial pathogenesis of transplant CAD.
View details for Web of Science ID A1995RN75900005
View details for PubMedID 7639157
Accelerated coronary artery disease is a major cause of late morbidity and mortality among heart-transplant recipients. Because calcium-channel blockers can suppress diet-induced atherosclerosis in laboratory animals, we assessed the efficacy of diltiazem in preventing coronary artery disease in transplanted hearts.Consecutive eligible cardiac-transplant recipients were randomly assigned to receive diltiazem (n = 52) or no calcium-channel blocker (n = 54). Coronary angiograms obtained early after cardiac transplantation and annually thereafter were used for the visual assessment of the extent of coronary artery disease. The average diameters of identical coronary artery segments were measured on the angiograms obtained at base line and at the first and second follow-up examinations.In the 57 patients who had all three angiograms, the average coronary artery diameter (+/- SD) 0.27 decreased in the group that received no calcium-channel blocker from 2.41 +/- 0.27 mm at base line to 2.19 +/- 0.28 mm at one year, and to 2.22 +/- 0.26 mm at two years (P < 0.001 for both years). The average diameter in the diltiazem group changed little from the base-line value of 2.32 +/- 0.22 mm (2.32 +/- 0.27 mm at one year and 2.36 +/- 0.22 mm at two years). The average change in the diameter of the segment differed significantly between the two treatment groups (P < 0.001), and the estimated effect of treatment changed only negligibly after adjustment for other relevant clinical variables. New angiographic evidence of coronary artery disease developed in 14 patients not given calcium-channel blockers, as compared with 5 diltiazem-treated patients (P = 0.082). Coronary stenoses greater than 50 percent of the luminal diameter developed in seven patients not given calcium-channel blockers, as compared with two patients given diltiazem; death due to coronary artery disease or retransplantation occurred in five patients in the group that did not receive calcium-channel blockers and none of those who received diltiazem.Our preliminary results suggest that diltiazem can prevent the usual reduction in the diameter of the coronary artery in cardiac-transplant recipients, but further follow-up will be required to determine whether diltiazem can decrease the long-term incidence of symptomatic coronary artery disease.
View details for Web of Science ID A1993KG62500003
View details for PubMedID 8417382