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Purpose of Review: Implementation of effective interventions often requires evidence regarding value, that is, whether they are worth what we pay for them. This review explores recent evidence concerning cost-effectiveness in familial hypercholesterolemia, and discusses the cause of, and likelihood of solutions to, the paucity of such evidence., Recent Findings: Cost-effectiveness analysis in familial hypercholesterolemia has been limited almost exclusively to adult populations. However, there is growing evidence that childhood intervention offers substantial benefit in terms of downstream health gains. Statin therapy in adults has been demonstrated to be cost-effective, but the range of novel agents that might be used will require de novo economic evaluation alongside exploration of their effect and safety profile., Summary: The familial hypercholesterolemia field has limited evidence regarding cost-effectiveness, which limits optimum allocation of resources. Economic evaluations are necessary to appraise new agents and optimal timing of management approaches. Evaluations often have substantial data demands; consequentially, their applicability to medical decision-making or policy will be partly determined by the availability of data, particularly those providing information about the long-term trajectory of health benefit from familial hypercholesterolemia treatment.

Background: There has been increasing interest in improving the outcome of coronary surgery while also seeking to minimize cost. It was the purpose of the present study to determine changes in the outcome and cost of CABG between 1988 and 1996., Methods and Results: The outcome and costs for 12,266 patients undergoing CABG were evaluated. Clinical data were gathered from the Emory Cardiovascular Database, and financial data were obtained from the UB92 formulation of the hospital bill. Charges were reduced to cost through the use of departmental cost-to-charge ratios. Costs were inflated to 1996 costs by using the medical care inflation rate. The patients became sicker, especially with increased incidences of hypertension, diabetes, and prior myocardial infarctions and a decrease in ejection fraction over the study period. Mortality rates tended to decrease from 4.7% to 2.7% (P = 0.07). After accounting for increasing indexes of severity of disease over the period, there was a significant decrease in death (OR, 0.90/y; P = 0.0001). Q-wave myocardial infarction rate fell from 4.1% to 1.3% (P < 0.0001). Mean hospital cost decreased from $22,689 to $15,987. Length of stay after surgery decreased from 9.2 to 5.9 days. After accounting for other variables, cost decreased by $1118 per year, and annual length of stay decreased by 0.55 day., Conclusions: The outcome of CABG continues to improve with declines in mortality rate and Q-wave myocardial infarction. This was accomplished while decreasing costs and length of stay. Whether these favorable trends will continue remains to be seen.

This study evaluates the effect of length of stay and baseline health status on health status and readmission rates 3 months after coronary artery bypass graft surgery. Baseline health status showed a trend toward worse scores for patients who were readmitted. Readmitted patients had longer lengths of stay, and worse 3-month health status scores, and women and patients with heart failure had higher readmission rates. It may be possible to identify patients at risk for readmission using clinical variables, length of stay, and health status. If a predictive model can be developed, then interventions can be developed and tested to decrease the rate of unplanned readmissions.

Background: Previous studies have demonstrated increased risk in patients undergoing coronary artery bypass surgery (CABG), but the effect of this increasing risk on outcomes has not been well documented. The purposes of this study were (1) to evaluate patients who had CABG from 1993 to 1995 (group III) and compare them with patients from 1981 through 1987 (group I) and 1988 through 1992 (group II) to determine if the trend toward higher-risk patients continued and (2) to evaluate what effect risk had on in-hospital outcomes., Methods and Results: Data were collected prospectively on patients undergoing CABG. Patients from the three time periods were compared by use of univariate and multivariate statistics. Risk models for mortality were developed by use of logistic regression. Significant changes were noted in the three time periods, with risk increasing over time. Increased risk was associated with increased mortality in group II, but mortality declined in group III despite the continued increase in patient risk. Group II had an increase in complications, with little change in group III. The actual mortality rate was lower than predicted in group III., Conclusions: Patients undergoing CABG are increasingly high risk. In-hospital mortality rates declined during the period from 1993 through 1995 and were lower than predicted despite the increase in risk. This decreased mortality rate may reflect greater experience in providing care to high-risk patients and improved myocardial protection and surgical and anesthetic techniques. Although continued analysis of patient risk and benefit is needed, researchers must be cognizant of the rapid changes in technology and knowledge and should correlate changes in the process of care with outcomes.

Background: Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring > or = 75 cases per year for operator "competency" are considered by some physicians to be arbitrary., Methods and Results: From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12,985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with > or = 30 cases per year. The average physician performed a mean +/- SD of 163 +/- 24 cases per year and had been practicing angioplasty for 8 +/- 5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r = .37, P = .01; for death, Q-wave infarction, or bypass surgery, r = .58, P < .001) than to linear caseload., Conclusions: In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.

Background: The immediate and long-term outcomes of reoperative coronary artery bypass surgery (CABG) (n = 1561) and catheter-based coronary intervention (angioplasty) (n = 2613) were compared in patients from Emory University Hospitals who had previous CABG., Methods and Results: The surgical and angioplasty procedures and statistical methods were standard. Data were collected prospectively and entered into a computerized database. Followup was by letter, telephone, or additional events resulting in readmission. In the angioplasty group, 2.9% required in-hospital CABG. Hospital mortality was 1.2% after angioplasty versus 6.8% after repeat CABG (P < .0001). Recurrent angina was noted frequently at about 4 years and was more common after angioplasty. One-, 5-, and 10-year mortalities were 11%, 24%, and 49% after CABG versus 6%, 22%, and 38% after angioplasty. Survival corrected for baseline differences did not vary with the choice of procedure. There were more additional procedures after angioplasty. Patients undergoing angioplasty may be divided into those with procedures only in native coronary arteries (n = 1545), only in vein grafts (n = 869), and a mixture (n = 199), with respective 10 year survivals of 66%, 56%, and 65% (P < .0001)., Conclusions: These patients have a high incidence of events both in-hospital and in the long term. Although initial mortality was higher after CABG, after baseline differences were accounted for, there was no difference in the long term. Patients more frequently have additional procedures after angioplasty. Choice of therapy should consider clinical and angiographic suitability and patient preference.

Background: The Emory Angioplasty Versus Surgery Trial (EAST) was designed to determine whether percutaneous transluminal coronary angioplasty (PTCA) is as effective as coronary artery bypass graft surgery (CABG) in restoring arterial perfusion capacity in eligible patients with multivessel disease., Methods and Results: Of 392 patients in EAST, 198 were randomized to PTCA and 194 to CABG. Index lesions (2.7 +/- 1.0 per patient) were those with > or = 50% stenosis judged treatable by both angioplasty and surgery. Coronary segments jeopardized by these index lesions were designated as index segments (4.4 +/- 1.4 per patient). Percent stenosis was measured by quantitative angiography at the point of greatest obstruction in the main perfusion path of each index segment. The EAST primary arteriographic end point was the percent of a patient's index segments with < 50% stenosis in the main perfusion pathways at 1 and 3 years. At baseline, the percent of index segments for which revascularization was attempted was 85% for PTCA and 98% for CABG (P < .0001). At 1 year, PTCA patients had a smaller percentage of successfully revascularized index segments than CABG patients (59% versus 88%, P < .001). At 3 years, the findings were similar but less striking (70% versus 87%, P < .001). When only "high-priority" index segments (2.1 +/- 1.6 per patient) were considered, baseline attempts were comparable (96% versus 99%, P = NS); despite this, CABG remained more successful at 1 (64% versus 93%, P < .001) and 3 (76% versus 89%, P < .01) years. However, the mean percent of index segments free of severe stenosis (> or = 70%) did not differ between PTCA and CABG patients at 3 years (93% versus 95%, P = NS). Furthermore, the frequency of patients with all index segments free of severe stenosis did not differ between the two groups at 1 (76% versus 83%, P = NS) or 3 (82% for both PTCA and CABG) years., Conclusions: In patients with multivessel disease, index segment revascularization was more complete with CABG than PTCA at both 1 and 3 years. However, when the physiological priority of the target lesion and the measured severity of the residual stenosis are taken into account, the advantage of CABG becomes less significant or nonsignificant. This may, in part, explain why these two strategies did not differ in terms of the EAST primary clinical end points over 3 years.

Background: The Emory Angioplasty Versus Surgery Trial (EAST) is a randomized trial that compares, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary surgery for multivessel coronary artery disease., Methods and Results: The primary end point was a composite of death, Q-wave myocardial infarction, and a large reversible thallium defect at 3 years. Multiple measures of quality of life also were made. Charges were assessed from the hospital UB-82 bills; professional charges were assessed from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were deflated to 1987 dollars. Costs were assessed for the initial hospitalization and the cumulative costs of the initial hospitalization and additional revascularization procedures for up to 3 years. There was no difference in mortality or the primary end point. Mean initial hospital charges were $12,654 for the PTCA group and $20,214 for the surgery group (P < .0001). Professional charges were 4538 for PTCA and $9426 for surgery (P < .0001). Three-year hospital charges were $19,047 for PTCA and $21,174 for coronary surgery (P < .0001). Three-year professional charges were $6412 for PTCA and $9861 for surgery (P < .0001). Three-year total charges were $25,458 for PTCA and $31,033 for surgery (P < .0001). Total 3-year costs were $23,734 for PTCA and $25,310 for coronary surgery (P < .0001). There were more hospitalizations for angina and more antianginal medications used in the PTCA group, which would further narrow the differences in cost., Conclusions: There was no difference in the primary end point or its components at 3 years. Although the primary procedural costs of coronary surgery are more than for coronary angioplasty, this cost advantage is largely, although probably not completely, lost by 3 years because of more frequent additional procedures and other resource consumption after a first revascularization by PTCA.

Background: Increasingly over the past several years, patients have returned after coronary surgery for reoperative procedures, and the experience has become substantial. In this report, we describe immediate- and long-term outcomes after reoperative coronary artery bypass graft surgery., Methods and Results: The source of data was the clinical database at Emory University. The surgical procedure and statistical methods were standard. Data were collected prospectively and entered into a computerized database. Follow-up was by letter, telephone, or hospital records documenting additional events resulting in readmission. In-hospital correlates of survival were determined by logistic regression, and long-term correlates were determined by Cox model analysis. There were 2030 patients with a mean age of 61 and a mean of 7.8 +/- 4.1 years since the first surgery. The mean ejection fraction was close to 50%, and the majority had three-vessel or left main disease. Urgent or emergency surgery was required in 16.6%. The internal mammary was used in 60.1%. Q-wave myocardial infarctions occurred in just over 5%. Neurological events increased from 1.2% at less than age 50 to 4.1% at more than age 70. The hospital mortality increased from 5.7% at less than age 50 to 10% at more than age 70, with an overall rate of 7.0%. Mortality was 5.7% for elective, 10.9% for urgent, and 16.4% for emergency cases. Angina was noted at follow-up in 41.3%. Urgent or emergency surgery, reduced ejection fraction, hypertension, older age, and female sex were univariate and multivariate correlates of in-hospital death. Diabetes was a univariate correlate only. Five- and 10-year survival rates were 76% and 55%, respectively. Five- and 10-year myocardial infarction-free survival rates were 63% and 40%, respectively. By 12 years, few patients were free of cardiac events. The univariate and multivariate correlates of long-term mortality were older age, reduced ejection fraction, hypertension, diseased vessels, presence of diabetes, congestive failure, and emergency surgery, with a strong trend for female sex. The use of the internal mammary artery was not a correlate for long-term mortality., Conclusions: Patients undergoing reoperative procedures have higher mortality initially and at long term than patients undergoing a first procedure. Expected mortality based on covariates may help in the decision of whether to perform reoperative coronary artery bypass graft surgery.

Background: Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized., Methods and Results: Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics., Conclusions: Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.

Children who survive liver transplantation (LT) suffer the adverse effects of life-long immunosuppression. In an attempt to minimize these effects, we have instituted a program of tapering immunosuppression, resulting in chronic monotherapy for children after LT. Seventy-three children ages 4 months to 19 years received LT between January 1987 and December 1992. Patient survival was 85% (62/73), with graft survival of 73%, at one year. Triple therapy with prednisone, cyclosporine, and azathioprine begun at transplant was tapered as follows: 1-2 mg/kg prednisone at discharge was reduced by .2 mg/kg every 2 months until a .2 mg/kg total was reached. Alternate-day steroids (.2 mg/kg) were begun at 1 year and discontinued at 1.5 years. AZA (1 mg/kg) was begun posttransplant and discontinued after any serious viral illness or by 1 year. Currently 37 survivors are > 18 months post-LT and were considered candidates for monotherapy. Monotherapy was attempted in 28 (76%), and 25 of these remain on monotherapy an average of 2 years later. All have normal liver function. After monotherapy and alternate-day steroids were achieved, 66% of children < 5th percentile for height at the time of transplant improved to greater than the 5th percentile. There were 3 (11%) patients who rejected while on monotherapy an average of 1.15 years after it was started. These patients had the following predisposing factors that decreased cyclosporine levels and led to rejection: common bile duct stricture, chronic and intermittent antibiotic administration for urinary tract infection, and noncompliance. In the 9 potential candidates not tapered to monotherapy, 6 have had recurrent acute or chronic rejection; 2 of these now receive FK506. We conclude that the majority of stable pediatric LT recipients may be safely tapered to chronic cyclosporine monotherapy. Increased growth is a major benefit of decreased steroid dosing in these children. Cyclosporine absorption and adequate levels are crucial for success of this approach.

Background: There is uncertainty as to the relative efficacy of coronary artery bypass graft surgery (CABG) in men and women. Differences between sexes may be of greater importance than heretofore because of increased frequency of risk factors for adverse outcome. It is the purpose of this study to examine the changing clinical characteristics of patients undergoing CABG and to determine the influence of these changes on the results of CABG in men and in women., Methods and Results: The source of data was the clinical database at Emory University Hospitals. The population comprised 13,368 patients (2648 women, 10,720 men) who had cardiac catheterization followed by CABG between 1974 and 1991. The patients were divided into the time periods 1974 through 1979 (532 women, 2792 men), 1980 through 1983 (727 women, 3151 men), 1984 through 1987 (695 women, 2619 men), and 1988 through 1991 (694 women, 2158 men). Data were collected prospectively and entered into a computerized database. The women were older (63 +/- 10 versus 58 +/- 10 years, P < .0001) and more frequently had diabetes (26.0% versus 15.4%, P < .0001). The in-hospital mortality was 3.8% in women and 1.6% in men. The multivariate correlates of death were older age, emergent surgery, reduced ejection fraction, female sex, diabetes, and more severe distribution of coronary arterial narrowings. Each of these risk factors for death became more prevalent, such that the mortality in men increased from 1.0% in 1974 through 1979 to 2.7% in 1988 through 1991, whereas the mortality in women increased from 1.3% in 1974 through 1979 to 5.4% in 1988 through 1991., Conclusions: The population undergoing CABG has aged, with correlates of in-hospital death becoming more common. The higher mortality in women could only partially be explained by other clinical variables. In addition, the risk of death after CABG has increased in women more than in men because women have consistently been older, have more emergent surgery and diabetes, and in recent years more women undergoing CABG have three-vessel or left main disease.

Background: Restenosis remains a critical limitation after coronary angioplasty. There is little information comparing long-term prognosis in patients who suffer from restenosis and others who do not. The purpose of this paper is to determine the clinical events in patients with restenosis or continued patency documented by restudy coronary arteriography., Methods and Results: The source of data was the clinical data base at Emory University. Patients who had previous coronary surgery and patients who underwent angioplasty in the setting of acute myocardial infarction were excluded. A total of 3,363 patients undergoing angiographic restudy 4 months to 1 year after angioplasty were compared with 3,858 not undergoing restudy. In the restudy population, 1,570 had restenosis and 1,793 had patent arteries at all sites dilated. The restenosis patients were older and had more hypertension, more diabetes, more severe angina, more multivessel coronary artery disease, more severe stenoses, and less satisfactory original results. At restudy, in patients without restenosis, 38.7% had angina versus 70.7% in patients with restenosis (p < 0.0001). There were few deaths in the first 6 months. At 6 years, the survival rate was 0.95 without restenosis and 0.93 with restenosis (p = 0.16). At 6 months and 6 years, freedom from myocardial infarction was 0.97 and 0.88 without restenosis and 0.93 and 0.85 with restenosis (p = 0.0001). On multivariate analysis, restenosis was an independent correlate of myocardial infarction but not mortality. At 6 months and 6 years, freedom from coronary bypass surgery was 0.99 and 0.94 without restenosis and 0.91 and 0.78 with restenosis (p < 0.0001). At 6 months and 6 years, freedom from repeat angioplasty was 0.96 and 0.76 without restenosis and 0.44 and 0.20 with restenosis (p = 0.0001). The highest event rates were noted in the patients with restenosis with recurrent chest pain. Patients not undergoing restudy differed somewhat from the study group, and there were far fewer repeat revascularization procedures in the group not undergoing restudy., Conclusions: Patients with restenosis are more likely to have recurrent angina pectoris. Although there is no or little difference in survival, there is a difference in myocardial infarction rate in the patients with and without restenosis. The low myocardial infarction and death rates in the group suffering restenosis may be related to repeat revascularization in these patients; the principal events in the restenosis population are frequent repeat revascularization procedures.

Six hundred ninety-nine patients have required emergency coronary artery bypass after failed elective percutaneous coronary angioplasty during the decade September 1980 through December 1990. This represents 4% of 9860 patients having 12,146 elective percutaneous coronary angioplasty procedures during this interval. Emergency coronary artery bypass was required for acute refractory myocardial ischemia in 82%. Hospital mortality rate for all patients was 3.1%; 3.7% in patients with refractory myocardial ischemia but 0.8% in patients without refractory myocardial ischemia, p = 0.08. Postprocedural Q-wave myocardial infarctions were observed in 21% versus 2.4%, p less than 0.0001, and intra-aortic balloon pumping was required in 19% with versus 0.8% without refractory myocardial ischemia, p less than 0.0001. Multivessel disease, p = 0.004, age older than 65 years, p = 0.005, and refractory myocardial ischemia, p = 0.08, interacted to produce the highest risk of in-hospital death. Follow-up shows that there have been 28 additional late deaths, including 23 of cardiac causes for a 91% survival at 5 years. Freedom from both late death and Q-wave myocardial infarction at 5 years was 61%. In the group going to emergency coronary artery bypass with refractory myocardial ischemia, the late cardiac survival was 90%, and in those without ischemia, 92% at 5 years, p = not significant. The MI--free survival in the group with refractory ischemia, however, was 56% versus 83% in the group without ischemia, p less than 0.0001. Multivariate analysis showed the highest late event rates for patients with Q-wave myocardial infarction at the initial emergency coronary artery bypass, age older than 65 years, angina class III or IV, and prior coronary bypass surgery. In spite of a continuing high incidence of early acute myocardial infarction and an increasing operative mortality rate (7%) in the latest 3 years cohort of patients, excellent late survival and low subsequent cardiac event rates demonstrate the lasting effectiveness of prompt, successful emergency coronary bypass surgery for failed percutaneous coronary angioplasty.

Background: Angioplasty of chronically totally occluded vessels has been associated with a success rate well below and restenosis rate well above that for angioplasty of stenosed segments. However, long-term clinical outcome after successful revascularization of a chronically totally occluded vessel has not been reported in detail., Methods and Results: Accordingly, data for 480 patients undergoing angioplasty for chronic total occlusion at Emory University Hospital, Atlanta, Ga., from 1980 to 1988 were analyzed for predictors of in-hospital procedural and clinical (procedural success and absence of in-hospital complications) success, restenosis, and 4-year clinical follow-up. The study population was grouped by procedural and clinical success and failure. The groups were then compared for outcome, both in hospital and long term. The initial clinical success rate was 66% (317 of 480 patients). Independent correlates of failure were the number of vessels diseased (p less than 0.001), vessel location of the lesion (p = 0.016), and absence of any distal antegrade filling (p = 0.002). Follow-up data revealed 98% cardiac survival and 96% overall survival at 4 years for the group as a whole. Freedom from myocardial infarction or cardiac death was significantly greater in patients with clinical success (93%) than with clinical failure (89%, p = 0.0044). In the successful group, 87% were free from coronary surgery after 4 years compared with 64% in the failure group (p less than 0.0001). Two thirds of the patients were free of angina at last follow-up. The presence of angina at follow-up was the same for patients successfully treated and for those with failed angioplasty, which may be related to the frequent use of coronary surgery in the failure group., Conclusions: In well-selected cases, the success rate for angioplasty of chronic total occlusion is acceptable. Furthermore, long-term clinical benefit is suggested by the high freedom from coronary surgery, myocardial infarction, and death in the patients who underwent successful revascularization.

Coronary surgery is being used increasingly in older and more seriously ill patients. To evaluate the importance of age in predicting complications and mortality after coronary surgery, the results in 13,625 patients undergoing coronary surgery were evaluated. There were 321 patients under the age of 40, 1,758 were 40-49, 4,167 were 50-59, 5,049 were 60-69, 2,184 were 70-79, and 146 were over 80. As patients aged the proportion of women increased, the prevalence of severe angina and congestive heart failure increased, and the severity of the distributions of the coronary stenoses increased. The incidence of the complications of neurological events, wound infections, and death rose in every decade after the age of 40 years. The incidence of death was 0.6% for patients aged 40-49, 1.5% for those aged 50-59, 1.9% for those aged 60-69, 5.0% for those aged 70-79, and 8.3% for those aged 80-89. Advanced age was the most significant independent correlate of neurological events, wound infections, and death. The other multivariate correlates of neurological events were diabetes, hypertension, and, surprisingly, angina class. Again surprisingly, the only other multivariate correlate of wound infections was angina class. The other multivariate correlates of death were emergent surgery, female gender, ejection fraction, severity of coronary disease, diabetes, and a history of congestive heart failure. Of interest, periprocedural Q wave myocardial infarction was independent of age. The most predictive and significant correlate of periprocedural myocardial infarction was emergent surgery; hypertension, absence of a previous myocardial infarction, and a normal ejection fraction were weaker correlates. The ability to predict any complication was relatively weak compared with the ability to predict death. The relative infrequency of coronary surgery over the age of 80 years suggests that there is already strong selection against surgery in octogenarians. In addition, the risk of death, and to some extent other complications, may be predicted in advance based on extensive patient experience.

Background: The introduction of percutaneous transluminal coronary angioplasty (PTCA) has changed the pattern of intervention in coronary artery disease. However, the long-term results in patients undergoing successful, elective, native-vessel PTCA are not yet fully characterized. Because the healing and subsequent proliferative response after angioplasty are time related, it was the purpose of the present study to determine the long-term outcome in patients whose dilated arteries have been demonstrated to be patent 4-12 months after successful, uncomplicated PTCA., Methods and Results: The patients were grouped on the basis of the 4-12 month catheterization into those whose vessels were angiographically "normal" or had luminal irregularities only at the PTCA sites (396 patients), those whose vessels also had luminal irregularities elsewhere with or without PTCA site luminal irregularities (680 patients), and those with significant obstructive disease (more than 50% diameter narrowing) at sites other than the PTCA sites (426 patients). Of 1,502 such patients, long-term follow-up was available in 1,491. At the time of the original angioplasty, the normal patients had a 1.8% incidence of multivessel disease; luminal irregularity patients, 9.4%; and obstructive disease patients, 58.7%. At angiographic restudy, 16.4% of the obstructive disease patients continued to have multivessel disease. The patients were followed for the events of death, myocardial infarction, coronary surgery, and repeat PTCA. The 6-year survival rate was 95%; cardiac survival, 96%; and freedom from all events, 65%. The strongest correlate of events during follow-up was the angiographic status of the undilated segments. At 6 years, freedom from cardiac events was noted in 77% of the normal group, 61% of the luminal irregularity group, and 55% of the obstructive disease group. Diabetes and hypertension were also independent correlates of events., Conclusions: Results from the present study show that associated disease in undilated segments is a strong predictor of late events in patients after successful, uncomplicated, reatenosis-free PTCA. However, the need for further revascularization was frequent even in patients without obstructive disease. Completeness of revascularization is appropriate when possible, and limiting progression of coronary disease at sites remote from those dilated should improve on these late results.

This study was performed to define the in-hospital and late clinical outcome at 5 years in 430 patients who had a failed elective percutaneous transluminal coronary angioplasty (PTCA) and underwent coronary artery bypass graft (CABG) surgery during their hospitalization. This group comprised 5.9% of 7,246 patients undergoing elective PTCA. CABG surgery was performed in 346 patients with ongoing myocardial ischemia (80.5%) and in 84 patients without ischemia (19.5%). Their mean age was 56 +/- 9 years, and 76.3% were male. One-vessel disease was present in 72.3%, and the mean left ventricular ejection fraction was 59 +/- 11%. Overall, 1.9 +/- 0.9 bypass grafts were placed. There was increased use of the internal thoracic artery in the nonischemic group. A new nonfatal postprocedural Q wave myocardial infarction occurred in 21.2% and occurred more frequently in the ischemic (25.4%) than in the nonischemic (3.6%) group (p less than 0.0001). There were six in-hospital deaths (1.4%), an incidence that did not differ between the two groups. Follow-up was 99.8% complete. There were 25 deaths (93.2 +/- 1.5%, 5-year survival), including 16 of cardiac cause (95.3 +/- 1.3%, 5-year cardiac survival). Q wave myocardial infarction occurred in 111 patients (91 in-hospital), and freedom from cardiac death or nonfatal myocardial infarction at 5 years was 71 +/- 3%. In the group going to CABG surgery with ongoing ischemia, the 5-year cardiac survival was 94.9 +/- 1.6%, and in the group without ischemia, the corresponding survival was 96.2 +/- 2.2%. By multivariate analysis, the presence of preoperative myocardial ischemia, pre-PTCA diameter stenosis less than 90%, and the presence of multiple-vessel disease correlated with the occurrence of cardiac death or nonfatal myocardial infarction at 5 years. At this large-volume center with extensive PTCA operator and surgical experience, the excellent survival and low event rates over 5 years support the concept that despite the failed elective PTCA procedure, there was little effect on long-term survival provided the patient underwent prompt successful surgical revascularization.

We investigated the relationship between regional myocardial blood flow (MBF) and segmental shortening in 17 open-chest dogs. The left anterior descending coronary artery was cannulated and perfused from the left carotid while measuring perfusion pressure. Graded occlusion was produced by a screw clamp. Extent of occlusion was monitored by perfusion pressure. Percent systolic shortening (% delta L) was measured using ultrasonic crystals implanted in normal and ischemic endocardium and ischemic epicardium. MBF was measured in ischemic and normal endocardium and epicardium with tracer microspheres. Dogs underwent 1 to 4 grades of coronary stenosis. Myocardial blood flow both to endocardium and epicardium was found to be linearly related to diastolic perfusion pressure below 50 mmHg (r = 0.803 and 0.748, respectively). Normalized % delta L (N% delta L) was best related to fraction normal zone MBF in the endocardium by the sigmoidal equation, N% delta L = e9.01 MBF-4.03/1 + e9.01 MBF-4.03. % delta L was only weakly related to myocardial blood flow in the epicardium (r = 0.584), and, in four dogs, % delta L was zero in the epicardium despite normal regional blood flow. However, % delta L in the epicardium was linearly related to % delta L in the endocardium (r = 0.78). Thus, endocardial wall motion is related to MBF by a sigmoidal relationship while epicardial wall motion is tethered to endocardial wall motion.

To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent systolic shortening, percent systolic elongation, and early diastolic shortening were calculated. Blood withdrawal decreased left ventricular preload, increased percent systolic elongation (from 6.9 +/- 3.1% to 9.9 +/- 3.5%) and early diastolic shortening (12.9 +/- 5.3% to 16.6 +/- 5.3%), and decreased percent systolic shortening. Blood transfusion increased left ventricular preload, decreased percent systolic elongation (to 5.2 +/- 1.8%) and early diastolic shortening (8.8 +/- 2.9%), and increased percent systolic shortening. Manipulation of loading did not change regional myocardial blood flow. In acutely ischemic myocardium, the tension-length loop showed an exponential upstroke during isovolumic systole and a nearly superimposed exponential downstroke during the isovolumic relaxation phase after systole, compatible with essentially passive movement as seen with an elastic material. The changes in loading conditions affected the tension-length curve to a very minor extent. The uniformity of the curve and its exponential shape explain the load-dependency of systolic bulging and segmental motion. It is concluded that systolic bulging depends on the change in the preload tension due to the compliant portion of tension-length curve, and that shortening of ischemic myocardium during the isovolumic relaxation phase is a completely passive phenomenon.

The effect of nifedipine on myocardial blood flow at various grades of coronary stenosis is unknown, Thus 22 open-chest dogs underwent carotid to left anterior descending perfusion with flow and perfusion pressure monitoring. Grades of coronary occlusion were defined by minimum diastolic perfusion pressure. six dogs (group 1) underwent moderate occlusion to 50 to 55 mm Hg diastolic perfusion pressure; (group 2), severe occlusion to 40 mm Hg perfusion pressure; and six (group 3), more severe occlusion at 25 mm Hg. Regional myocardial blood flow was measured with radioactive microspheres before and after the intracoronary injection of 10 microgram of nifedipine. In group 1, nifedipine induced epicardial hyperemia and little change in endocardial flow in the ischemic zone. In group 2, nifedipine induced epicardial hyperemia from 1.06 to 1.39 mg/g per min, but endocardial flow decreased from 0.70 to 0.60 ml/g per min. In group 3, there was no change in blood flow. Thus the effect of nifedipine on myocardial blood flow depends on the extent of occlusion. Furthermore for certain degrees of occlusion, redistribution of blood flow from endocardium to epicardium has been shown to occur.

The introduction of aortic balloon valvuloplasty has prompted review of established techniques to treat aortic valve disease. To this end, the surgical results were reviewed for 1,148 patients undergoing aortic valve replacement, with and without associated coronary artery bypass grafting, for aortic stenosis between January 1, 1975 and September 1, 1987. The overall death rate was 4.6%. The neurological event rate (stroke or reversible ischemic event) was 4.2%, the myocardial infarction rate was 3.5%, and 30.7% had a hospital stay in excess of 10 days. Mortality for isolated elective aortic valve replacement rose from 2.5% for patients under age 70 to 7.3% for those over age 70. Mortality for elective aortic valve replacement plus coronary bypass was 3.8% for patients under age 70 and 11.6% for patients over age 70. The neurological event rate rose from 3.0% to 8.4% and the prolonged length of stay from 28% to 42%. By stepwise logistic regression analysis, the predictors of in-hospital mortality were age and emergent surgery. Age was the only multivariate predictor of neurological events. The year of surgery and emergent status were the multivariate predictors of prolonged length of hospital stay. Aortic valve replacement for aortic stenosis is a well-established technique with low neurological event rates and mortality, which may be predicted in advance. Newer techniques must be considered in light of data such as these.

The length of hospital stay after coronary surgery was studied in 4,683 patients undergoing cardiac catheterization followed by coronary surgery at Emory University Hospital or Crawford Long Hospital between the years 1981 and 1986. Length of stay after coronary surgery had a median and modal value of 7 days. There was, however, a long statistical tail of patients with a prolonged length of stay extending out to more than 180 days. Prolonged length of stay (greater than 10 days) could be correlated with preprocedural variables such as age, elective versus emergency status, angina class, ejection fraction, and gender. Length of stay increased from a mean of 6.9 +/- 1.4 days under the age of 40 years to 10.9 +/- 12.1 days over the age of 70 years (p less than 0.0001). Length of stay was correlated with the periprocedural variables of wound infection, neurologic event, arrhythmias, pneumonia, postoperative myocardial infarction, mortality, and pericarditis. Length of stay increased from 8.8 +/- 9.6 days without a neurologic event to 21.1 +/- 17.9 days with a neurologic event (p less than 0.0001). Similarly, without a wound infection, the average stay was 8.7 +/- 8.9 days; with a wound infection, the average stay was 32.2 +/- 25.8 days (p less than 0.0001). The correlates of prolonged stay were tested in another population comprising 781 patients undergoing cardiac catheterization followed by coronary artery bypass grafting in 1987. The predictors of prolonged stay in the 1987 population were wound infection, pneumonia, arrhythmias, age, neurologic events, postoperative infarction, and ejection fraction. Thus, length of hospital stay after coronary surgery may be predicted by multiple preprocedural and periprocedural variables.(ABSTRACT TRUNCATED AT 250 WORDS)

The change in left ventricular radionuclide ejection fraction after acute occlusion of the left anterior descending (LAD) or circumflex (LC) coronary artery was compared with the ultimate histologic extent of myocardial infarction in conscious dogs. The acute change in ejection fraction correlated with size of infarction in 14 dogs with occlusions of the LAD coronary artery (r = .89, y = 1.12x + 14.2) and in 27 dogs with occlusions of the LC coronary artery (r = .71, y = 0.73x + 7.9); the slope of the regression equation was greater (p less than .05) for those with LAD than for those with LC occlusions. Multivariate analysis revealed no independent contribution of left ventricular weight, the subendocardial extent of infarction, or change in heart rate to the acute change in ejection fraction. These data indicate that the decrease in ejection fraction after coronary occlusion is determined primarily by the size of the ischemic area, which also determines size of infarction. In dogs instrumented over a long term, infarcts in the LAD myocardial distribution result in greater decreases in ejection fraction than infarcts of comparable size in the LC distribution.

Nifedipine has been proposed as an agent to preserve viability and function of ischemic myocardium. We studied 23 open-chest dogs that underwent carotid-to-left anterior coronary artery perfusion with flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the ischemic and nonischemic endocardium. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to 25 mm Hg diastolic perfusion pressure. Ten dogs received intracoronary nifedipine, 10 micrograms, and 13 dogs received i.v. nifedipine, 3 micrograms/kg/min. Nifedipine resulted in an increase in segmental shortening in both groups, but nonischemic zone shortening did not change in either group. Nifedipine did not affect myocardial blood flow in the ischemic zone, but increased flow in the nonischemic zone in the group that received i.v. nifedipine. Thus, nifedipine appears to have a direct beneficial effect on ischemic myocardium.

To study the influence of left ventricular (LV) late diastolic filling on the A wave of the LV pressure, simultaneously recorded echocardiographic LV dimensions and high-fidelity LV pressure measurements were taken in 24 patients. Group 1 comprised eight patients without LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) less than or equal to 13 mm Hg. Group 2 comprised 16 patients with LVH secondary to aortic stenosis, idiopathic hypertrophic subaortic stenosis, or hypertension and increased LVEDP. Patients in group 2 had significantly thicker left ventricles, decreased mitral E-to-F slopes, and larger A waves in the LV pressure curve. On the basis of end-diastolic chamber stiffness, we divided group 2 into two populations: 12 patients (group 2A) with end-diastolic chamber stiffness similar to that in group 1, and four patients (group 2B) with markedly elevated end-diastolic chamber stiffness. Patients in group 2A had a larger atrial contribution to LV filling than those with markedly abnormal stiffness (group 2B). Therefore, in LVH an increased A wave in the LV pressure may be related to either elevated end-diastolic chamber stiffness or augmented left atrial volume transport.

This study was performed to define the 5 year clinical status of 427 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) in 1981. Their mean age was 54 +/- 10 years (+/- 1 SD). Sixty-one percent had unstable angina, 23% had prior myocardial infarction, 86% had one-vessel disease, and 92% had normal left ventricular function. Sixty-seven percent of patients had left anterior descending artery stenosis. Angiographic success was achieved in 84% of patients. Coronary bypass surgery was required in 9.6% of patients, in 5.9% as an emergency procedure. There were no in-hospital deaths. Follow-up at 5 years was 100% complete. There were 15 late deaths (96.3 +/- 1.0% survival), including seven of cardiac cause (98.1 +/- 0.7% cardiac survival). Myocardial infarction occurred in 24 patients (94% freedom from myocardial infarction), coronary bypass surgery was required in 63 (84% freedom from bypass surgery), and 365 patients (85%) were asymptomatic at follow-up. At 5 years, 83 patients (20%) had required an additional PTCA. Unstable angina pectoris and proximal left anterior descending coronary artery stenoses were present in 162 patients. The overall survival and cardiac survival in this subset was 94.4 +/- 1.8% and 98.1 +/- 1.1%, respectively. The excellent survival and low event rates over 5 years in this population support the concept that PTCA is safe and effective for patients with symptomatic angina pectoris, single-vessel disease, and normal left ventricular function.

This study was performed to determine the procedural characteristics and in-hospital complications associated with failed percutaneous transluminal coronary angioplasty that necessitates coronary artery bypass graft surgery. The study population consisted of 316 patients from 1980 to 1986; 202 patients (64%) had emergency coronary artery bypass graft surgery and the remainder elective surgery during the same hospitalization. Mean age of the population was 56 +/- 9 years, 69% were male, and 69% had single-vessel disease. The failed percutaneous transluminal coronary angioplasty occurred most commonly on the first vessel attempted and was usually secondary to coronary artery dissection. Analysis of surgical technique revealed increased use of intra-aortic balloon pump in the emergency group (24% vs. 2% in the elective group, p less than 0.05). Overall, 2.0 +/- 1.0 (mean +/- SD) bypass grafts were placed, with increased use of the internal thoracic artery in the elective (32%) versus the emergency group (20%, p less than 0.05). A new, nonfatal, postprocedural Q-wave myocardial infarction occurred in 18% and developed more frequently in the emergency (27%) than in the elective (4%) cohorts. There were six in-hospital deaths (1.9%), an incidence which did not differ between groups. This analysis revealed a significant difference in operative technique between the emergency and the elective coronary artery bypass graft patients. Preoperative ischemia was significantly related to the development of the Q-wave myocardial infarction, yet not to in-hospital mortality.(ABSTRACT TRUNCATED AT 250 WORDS)