Edward D. Folland

A Comparison of Angioplasty with Medical Therapy in the Treatment of Single-Vessel Coronary Artery Disease

BACKGROUND Despite the widespread use of percutaneous transluminal coronary angioplasty (PTCA), only a few prospective trials have assessed its efficacy. We compared the effects of PTCA with those of medical therapy on angina and exercise tolerance in patients with stable single-vessel coronary artery disease. METHODS Patients with 70 to 99 percent stenosis of one epicardial coronary artery and with exercise-induced myocardial ischemia were randomly assigned either to undergo PTCA or to receive medical therapy and were evaluated monthly. The patients assigned to PTCA were urged to have repeat angioplasty if their symptoms suggested restenosis. After six months, all the patients had repeat exercise testing and coronary angiography. RESULTS A total of 107 patients were randomly assigned to medical therapy and 105 to PTCA. PTCA was clinically successful in 80 of the 100 patients who actually had the procedure, with an initial reduction in mean percent stenosis from 76 to 36 percent. Two patients in the PTCA group required emergency coronary-artery bypass surgery. By six months after the procedure, 16 patients had had repeat PTCA. Myocardial infarction occurred in five patients assigned to PTCA and in three patients assigned to medical therapy. At six months 64 percent of the patients in the PTCA group (61 of 96) were free of angina, as compared with 46 percent of the medically treated patients (47 of 102; P less than 0.01). The patients in the PTCA group were able to increase their total duration of exercise more than the medical patients (2.1 vs. 0.5 minutes, P less than 0.0001) and were able to exercise longer without angina on treadmill testing (P less than 0.01). CONCLUSIONS For patients with single-vessel coronary artery disease, PTCA offers earlier and more complete relief of angina than medical therapy and is associated with better performance on the exercise test. However, PTCA initially costs more than medical treatment and is associated with a higher frequency of complications.

Assessment of left ventricular ejection fraction and volumes by real-time, two-dimensional echocardiography. A comparison of cineangiographic and radionuclide techniques.

Five different algorithms for determining left ventricular (LV) ejection fraction (EF) and volumes from two-dimensional echocardiographic examination (TDE) were compared with standard methods for obtaining EF and volume from x-ray cineangiography (cine) and EF from radionuclide ventriculography (RVG) in 35 patients. Although all methods correlated positively, the degree of correlation varied with the algorithm used. For EF determination, TDE algorithms (especially those using multiple planes of section) were superior to unidimensional algorithms commonly used with M-mode echocardiography. The best algorithm (modified Simpsons rule) correlated well enough with cine EF (r = 0.78; SEE 0.097) and RVG EF (r = 0.75; SEE 0.087) to make clinically useful estimates. TDE volumes also correlated meaningfully with cine end-diastolic and end-systolic volumes (r = 0.84; n = 70) but were associated with a large standard error of the estimate (43 ml) and offered less advantage over unidimensional volume estimations. Quantitative application of TDE appears to be a useful noninvasive method of evaluating LVEF, but is not as useful for estimating LV volumes.

Percutaneous transluminal coronary angioplasty versus medical therapy for stable angina pectoris : Outcomes for patients with double-vessel versus single vessel coronary artery disease in a Veterans Affairs cooperative randomized trial

Abstract Objectives. This study sought to assess outcomes of men with double-vessel coronary artery disease randomly assigned to treatment by percutaneous transluminal coronary angioplasty (PTCA) or medical therapy, compared with previously reported outcomes for men with single-vessel disease. Background. We previously reported that PTCA provides better symptom relief and treadmill performance than medical therapy for men with stable angina pectoris due to single-vessel disease. Whether this advantage applies to patients with double-vessel disease is unknown. Methods. Male patients (n = 328) with stable angina pectoris and ischemia on treadmill testing were randomly assigned to PTCA or medical therapy; 101 patients had double-vessel disease, and 227 had single-vessel disease. Symptoms, treadmill performance, quality of life score, coronary stenosis and myocardial perfusion were compared at baseline and at 6 months. Patients were followed up for up to 6 years and underwent additional treadmill testing 2 to 3 years after randomization. Results. PTCA-treated and medically treated patients with double-vessel disease experienced comparable improvement in exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with baseline. This contrasts with greater advantages favoring PTCA by these criteria in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6 months persisted at late follow-up. Patients undergoing double-vessel dilation had less complete initial revascularization (45% vs. 83%) and greater average stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with double-vessel disease showed less improved myocardial perfusion imaging (59% vs. 75%). Conclusions. PTCA is beneficial in male patients with double-vessel disease; however, we cannot demonstrate the same advantage over medical therapy seen in similar patients with single-vessel disease. Less complete revascularization and greater restenosis for patients having multiple dilations would account for these findings. Alternatively, a type 2 error might be operative. Technical advances since completion of this trial might improve these outcomes. These findings warrant further investigation in a larger trial. (J Am Coll Cardiol 1997;29:1505–11)

Quantitative detection of regional left ventricular contraction abnormalities by two-dimensional echocardiography. II. Accuracy in coronary artery disease.

The quantitative approaches to the assessment of regional left ventricular (LV) function described in the preceding paper were applied in a well-defined population of patients with coronary artery disease. Two groups were chosen by electrocardiographic and angiographic criteria: group 1 had infarction and regional wall motion abnormalities and group 2 had no infarction and normal wall motion. Sensitivity to detect wall motion defects, specificity to correctly categorize normal segments, and overall predictive accuracy were evaluated for each two-dimensional echocardiographic approach. In addition, the ability of each method to localize regional contraction defects properly was evaluated. Area methods yielded better predictive accuracy than linear methods (87-95% vs 76-84%). No significant differences in accuracy were noted between quadrant and octant approaches. The fixed external-axis system was superior to a floating one for localizing contraction defects. We conclude that an area-based method, using a fixed-axis system and either octant or quadrant image subdivision, provides the best combination of predictive accuracy in categorizing LV segments as normal or abnormal and the greatest ability to localize LV regional abnormalities.

A Comparison of Quality of Life Scores in Patients With Angina Pectoris After Angioplasty Compared With After Medical Therapy Outcomes of a Randomized Clinical Trial

Background Evaluations of therapy for the treatment of angina have traditionally consisted of a combination of objective measures, such as exercise tolerance, and subjective markers, such as angina attack rate. Recently, the need to assess how patients feel-their quality of life (QOL)-has been regarded with increasing importance. Standard instruments are available to assess QOL and its change after therapeutic intervention. Although QOL instruments have been used to assess the efficacy of percutaneous transluminal coronary angioplasty (PTCA), they have not been used previously to compare the impact of PTCA with that of medical therapy in patients with angina pectoris. We report on the changes in self-assessed QOL among patients randomly assigned to treatment by PTCA or medical therapy and relate these measurements to changes in exercise performance and coronary angiograms. Methods and Results Patients with stable angina, a positive exercise tolerance test, and at least 70% stenosis (index lesion) in the proximal two thirds of one major coronary artery were randomly assigned to receive PTCA or medical therapy. Six months after randomization, each patient underwent repeat exercise testing and coronary angiography. Before randomization and at the 6-month visit, patients completed a self-administered QOL questionnaire that measured physical functioning and psychological well-being. We compared the changes in QOL with changes between the baseline and 6-month exercise tests, stratified by terciles (decrease in duration, 0- to 2-minute increase, and >2-minute improvement). We also stratified patients by whether there was more or less than 2 SD change (18.8%) in diameter stenosis of the index lesion (initial minus follow-up angiogram), and we related these to changes in QOL measures. One hundred eighty-two patients with one-vessel disease completed baseline and 6-month questionnaires. At baseline, there were no differences in any QOL measurements between treatment groups. At the 6-month follow-up visit, there was greater improvement in both physical functioning and psychological well-being scores for patients receiving PTCA (+7.36±15.6, PTCA ; +1.98±14.7, medical therapy; P<.02). Improvement in QOL variables was noted only in patients demonstrating an increase in exercise performance. Also, patients assigned to either treatment whose angiograms demonstrated more than 18.8% improvement in index lesion percent stenosis experienced a significant increase in their QOL scores. Conclusions This was the first study of the relative changes in QOL measures assessed with the use of previously validated and standardized instruments in patients randomly assigned to treatment with PTCA or medical therapy. Patients assigned to PTCA demonstrated a significantly greater improvement in both physical and psychological measures. This improvement was noted in patients whose exercise performance improved and whose angiograms demonstrated an improvement in lesion severity. (Circulation. 1995 ;92 :1710-1719.)

Serial evaluation of myocardial thickening and thinning in acute experimental infarction: identification and quantification using two-dimensional echocardiography.

Regional left ventricular function was studied serially by quantitative two-dimensional echocardiography (2-D echo) in 20 dogs after left anterior descending coronary artery ligation. Normal values for regional myocardial thickening were established in 20 healthy dogs and used as a standard to recognize abnormally contracting segments (ACS). In normal hearts, the mean percent thickening tended to increase from base (25.8%) to apex (34.0%), but showed considerable diversity from segment to segment (range 20.0-40.0%); nevertheless, at least some degree of thickening was seen in every segment. After coronary occlusion, myocardial segments either thinned or failed to thicken. At the papillary muscle level, there was an improvement in function between 2 and 48 hours, with thinning at 2 hours and thickening at 48 hours. Tissue infarct size (IS) determined at 48 hours was related to IS derived from a weighted summation of ACS at 2, 24 and 48 hours. At 2 hours, ACS considerably overpredicted and correlated poorly with tissue IS (25.3% vs 13.4%; r = 0.60); by 48 hours, IS predicted by ACS had decreased to 15.3% (p < 0.05) and had an improved, but only fair correlation with tissue IS (r = 0.73, SEE = 4.9%).We conclude that there is considerable heterogeneity to myocardial thickening by 2-D echo, but failure to thicken is not seen in the normal dog heart. In many dogs, the extent of myocardial dysfunction 2 hours after coronary ligation exceeds that seen later. Tissue IS is difficult to predict accurately from ACS. Since the amount of muscle dysfunction is not necessarily equivalent to the amount of tissue necrosis in acute myocardial infarction, ACS may be more appropriately used to track the course of infarction rather than to predict IS.

Long-term benefit of thrombolytic therapy in patients with pulmonary embolism

A total of 23 of the 40 patients who had angiographically proven pulmonary embolism and who had initially been randomized to an IV infusion of heparin (n = 11) or a thrombolytic agent (urokinase or streptokinase, n = 12) were restudied after a mean follow-up of 7.4 years to measure the right-sided pressures and to evaluate their response to exercise during supine bicycle ergometry. Results showed that, at rest, the pulmonary artery (PA) mean pressure and the pulmonary vascular resistance (PVR) were significantly higher in the heparin group compared with the thrombolytic group (22 vs. 17 mmHg, p < 0.05, and 351 vs. 171 dynes s- 1 cm- 5, p < 0.02, respectively). During exercise both parameters rose to a significantly higher level in the heparin group (from rest to exercise, PA: 22-32 mmHg, p < 0.01; PVR: 351-437 dynes s- 1 cm- 5, p < 0.01, respectively), but not in the thrombolytic group (rest to exercise, PA: 17-19 mmHg, p = NS; PVR: 171-179 dynes s- 1 cm- 5, p = NS). It is concluded that thrombolytic therapy preserves the normal hemodynamic response to exercise in the long term and may prevent recurrences of venous thromboembolism and the development of pulmonary hypertension.

Evaluation of exercise thallium scintigraphy versus exercise electrocardiography in predicting survival outcomes and morbid cardiac events in patients with single- and double-vessel disease. Findings from the Angioplasty Compared to Medicine (ACME) Study.

OBJECTIVES We sought to evaluate the prognostic ability of cardiac exercise stress tests in predicting cardiac mortality and morbidity in a low risk group of patients with established coronary artery disease (CAD). BACKGROUND Although previous studies have demonstrated the superior value of stress nuclear cardiac scintigraphy in the prognosis of patients with CAD, none of these studies have focused on patients with a proven angiographic low risk profile (i.e., single- and double-vessel CAD). METHODS Three hundred twenty-eight patients with documented single- and double-vessel disease were treated by random assignment to percutaneous transluminal coronary angioplasty or medical therapy in the Angioplasty Compared to Medicine (ACME) trial. Six months after randomization, maximal symptom-limited exercise tests were performed with electrocardiography (n = 300) and thallium scintigraphy (n = 270). Patients were followed up for a minimum of 5 years thereafter. RESULTS A reversible thallium perfusion deficit documented after 6 months of either therapy was associated with an adverse mortality outcome (18% mortality rate with a reversible thallium perfusion defect and 8% mortality rate with no reversible thallium perfusion deficit, p = 0.02). Moreover, an important mortality gradient was demonstrated in relation to the number of reperfusing defects (0 = 7%, 1 to 2 = 15%, >3 = 20%, p = 0.04). Exercise electrocardiography did not predict this mortality outcome. CONCLUSIONS A reversible thallium perfusion deficit demonstrated 6 months after medical therapy or coronary angioplasty is a valuable prognostic marker in patients with angiographically documented single- and double-vessel disease and is superior to exercise electrocardiography in this regard.

Comparison of outcome after valve replacement with a bioprosthesis versus a mechanical prosthesis: Initial 5 year results of a randomized trial

The Veterans Administration Cooperative Study on Valvular Heart Disease was organized to compare survival and incidence of valve-related complications between patients receiving a bioprosthesis (the Hancock porcine heterograft) and a mechanical prosthesis (the Björk-Shiley spherical disc valve). Five hundred seventy-five patients undergoing single aortic or mitral valve replacement were randomized at surgery to one of the two valve types. At an average follow-up of 5 years (range 3 to 8) there are no statistically significant differences in survival between patients with the two valve types in the aortic valve replacement group. There is a statistically nonsignificant trend toward improved survival in patients undergoing mitral valve replacement with a bioprosthesis compared with a mechanical prosthesis (5 year survival probability was 0.70 +/- 0.05 and 0.58 +/- 0.06, respectively). Fatal and nonfatal valve-related complications occurred significantly less frequently in patients with a bioprosthesis compared with a mechanical prosthesis for both mitral and aortic valve replacement. Five year complication-free probability was 0.67 +/- 0.05 and 0.45 +/- 0.06, respectively, for patients with mitral valve replacement and 0.63 +/- 0.04 and 0.53 +/- 0.04, respectively, for those with aortic valve replacement. The difference in overall complication rates was largely due to the increased number of clinically significant but nonfatal bleeding episodes in patients receiving a mechanical prosthesis. Adjustment for differences in baseline characteristics between patients receiving a mitral mechanical prosthesis and a mitral bioprosthesis reduced the statistical significance of the difference in both mortality and complications.

Two- to three-year follow-up of patients with single-vessel coronary artery disease randomized to PTCA or medical therapy (results of a VA cooperative study)

Despite increasing use of percutaneous transluminal coronary angioplasty (PTCA) to treat stenotic coronary artery disease, there are relatively few prospective studies evaluating its long-term effectiveness. We prospectively randomized 212 stable patients with provocable myocardial ischemia and single-vessel subocclusive coronary disease to receive primary therapy with either PTCA or medical therapy. This report presents the clinical follow-up of these patients at a mean, after randomization, of 2.4 years for interview and 3.0 years for exercise testing. Of the 212 patients originally randomized, 175 received an extended follow-up interview, and 132 underwent exercise testing; 62% of patients in the PTCA group were angina free compared with 47% of patients in the medical group (p <0.05). Furthermore, exercise duration as measured by treadmill testing was prolonged by 1.33 minutes over baseline in the PTCA group, whereas it decreased by 0.28 minutes in the medical group (p <0.04). Although the angina-free time on the treadmill was not different (p=0.50), fewer patients in the medical group developed angina on the treadmill at 3 years than those in the PTCA group (p=0.04). By 36 months, excluding the initial randomized PTCA, use of PTCA and use of coronary artery bypass surgery were not different in the 2 treatment groups. These data indicate that some of the early benefits derived from PTCA in patients with single-vessel coronary artery disease are sustained, making it an attractive therapeutic option for these patients.