Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias.

BACKGROUND: In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance. METHODS: The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years). RESULTS: At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up. CONCLUSION: At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.

Program on the Surgical Control of the Hyperlipidemias (POSCH): patient entry characteristics. The POSCH Group.

The entry characteristics of patients in the Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized, controlled, clinical trial, are described in this article. The primary objective addressed by POSCH was whether lowering total plasma cholesterol by partial ileal bypass surgery results in a reduction in mortality and morbidity in post-myocardial infarction patients. Between 1975 and 1983, 838 patients between the ages of 30 and 64 years were randomized into POSCH. The mean age at entry was 51 years, and 91% of the patients were men. The mean time between myocardial infarction and entry was 2.2 years. The mean baseline total plasma cholesterol was 251 mg/dl, with a mean LDL-cholesterol of 179 mg/dl and a mean HDL-cholesterol of 40 mg/dl. Significant disease (greater than or equal to 50% occlusion) of one or more major coronary arteries was found in 91% of the patients. In addition to a description of the POSCH patient population at entry, comparisons of the POSCH patient population to populations of participants in other lipid-lowering trials are presented to provide a perspective on how POSCH relates to these trials.

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)

BACKGROUND AND METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS: When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS: Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression.

Flow characteristics of bioprosthetic heart valves.

A review of the in vivo and in vitro fluid dynamic performance of three bioprosthetic heart valves is presented. Data on Hancock porcine valves (standard models 242 aortic and 342 mitral and modified orifice model 250 aortic), Carpentier-Edwards porcine valves (model 2625 aortic and 6625 mitral), and the Ionescu-Shiley pericardial valve are reviewed. These valves were chosen because of their past or present popularity in clinical use and because of the variation in fluid dynamic performance reported by different investigators. The flow parameters that are reported include in vivo and in vitro mean pressure drop, cardiac output or cardiac index, regurgitant volume, effective orifice area, and performance index. These data provide a framework for differentiation of normal and abnormal bioprosthetic valve function.

Efficacy of propranolol therapy after acute myocardial infarction related to coronary arterial anatomy and left ventricular function.

The effect of the beta-adrenergic blocking agent propranolol on morbidity and mortality risk after acute myocardial infarction was studied relative to coronary anatomy and left ventricular (LV) ejection fraction in a subset of 406 patients participating in a randomized study of 3,837 patients in the Beta Blocker Heart Attack Trial (BHAT). Median follow-up for this subset of patients was 28 months. The mortality rate was 2% (2 of 100) in patients with 2- and 3-vessel coronary artery disease taking propranolol and 10% (12 of 126) in those taking placebo (p less than 0.02). In patients with 2- and 3-vessel coronary artery disease with decreased LV function (defined as ejection fraction less than 50%), no patient taking propranolol died, whereas 17% (7 of 42) taking placebo died (p less than 0.04). The salutary effect of propranolol on mortality in the larger BHAT after acute myocardial infarction also was evident in this population studied in regard to their coronary and LV anatomy and function.

Efficacy of bucindolol in systemic hypertension.

The hemodynamic effects of oral bucindolol, a non-selective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilating properties, were studied at rest and during handgrip exercise with a flotation-directed pulmonary artery catheter in 12 patients with mild to moderate essential hypertension. After the initial dose of 150 mg of bucindolol, blood pressure (BP) was significantly reduced and cardiac output was increased (from 5.9 +/- 0.8 to 6.8 +/- 1.6 liters/min) in the supine position and during exercise (p less than 0.05). Systemic vascular resistance was reduced (from 1,555 +/- 339 to 1,311 +/- 467 dynes s cm-5, p less than 0.01) at rest and without significant changes during exercise. There were increases in heart rate (13 +/- 13%, p less than 0.01) and right atrial (69 +/- 77%, p less than 0.05), pulmonary arterial (38 +/- 24 %, p less than 0.001) and pulmonary artery wedge pressures (62 +/- 46%, p less than 0.001) during exercise. Bucindolol did not change these variables at rest or during exercise. Bucindolol increased plasma norepinephrine levels both at rest (from 330 +/- 151 to 588 +/- 320 ng/liter, p less than 0.01) and during exercise (from 468 +/- 220 to 685 +/- 390 ng/liter, p less than 0.05). After 4 weeks of bucindolol with doses of 50 to 200 mg 3 times daily, BP was reduced in both supine and standing positions (mean arterial BP of 11 +/- 7% [p less than 0.001] and 11 +/- 6% [p less than 0.001], respectively), without changes in cardiac output, systemic vascular resistance or plasma norepinephrine level.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow characteristics of four commonly used mechanical heart valves.

The in vivo and in vitro fluid dynamic performance of 4 mechanical heart valves was reviewed: Starr-Edwards silicon-rubber ball valves (models 1200/1260 aortic and 6120 mitral valves), Björk-Shiley tilting disc valves (standard spherical model, modified and unmodified convexo-concave [60 degrees and 70 degrees C-C] models), the Medtronic-Hall (Hall-Kaster) tilting disc valve and the St. Jude Medical bileaflet valve. These valves were chosen because of their past or present popularity in clinical use and because they encompass most of the basic mechanical valve designs used during the past 2 decades. The flow measurements reported include in vivo and in vitro mean pressure drop, cardiac output or cardiac index, regurgitant volume, effective orifice area and performance index.

Clinical data versus noninvasive testing as an estimate of coronary status.

The step from coronary angiography to surgery is taken primarily on the basis of the ejection fraction (EF) and number of diseased vessels (NV), taken jointly as coronary status (CS). This study reviewed (1) how well EF, NV and CS are estimated from clinical data, (2) how much improvement is gained by adding noninvasive data, (3) how good this model is when applied to a larger cohort and (4) whether the decision to angiography can be made on the basis of CS estimated from clinical data alone. A quantitative definition of CS was established as a principal component of EF and NV. Estimates of EF, NV and CS were made from clinical data of 60 patients. Correlations with the actual values were EF 87%, NV 93% and CS 93%. When noninvasive data were added to this model, the correlations increased to EF 95%, NV 99% and CS 98%. When the clinical data model was applied to 169 patients, the correlations decreased to EF 77%, NV 71% and CS 74%. CS estimated from clinical data alone was set up as a test for angiography for 169 patients. This test had a sensitivity of 98% and a specificity of 63%, demonstrating the feasibility of using clinical data alone in deciding angiography.

Mitral E point septal separation: a reliable index of left ventricular performance in coronary artery disease.

The diagnostic value of E point septal separation (EPSS) was assessed in 108 patients with coronary artery disease who underwent coronary angiography and M-mode echocardiography within a 2-year period at LAC/USC Medical Center. In patients with anterior myocardial infarction, EPSS correlated well with angiographic ejection fraction, with a specificity of 85% and sensitivity of 82%. In inferior myocardial infarction, a 21% frequency of falsely elevated EPSS values was encountered; the sensitivity for detecting reduced ejection fraction was 100% and the specificity was 67%. In combined anterior and inferior myocardial infarction, EPSS accurately estimated abnormal ejection fractions with a sensitivity and specificity of 100%. An abnormal EPSS (more than 7 mm) was found to be more sensitive (87%) and specific (75%) in detecting individuals with angiographically reduced ejection fraction (less than 50%) compared to other echocardiographic indices of pump function. Importantly, EPSS was effective in estimating left ventricular function in the presence of left bundle branch block, paradoxical septal motion, and angiographic septal, posterior, and anterior wall motion abnormalities.

Late, late doxorubicin cardiotoxicity.

Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.

Thyrotoxicosis presenting as unstable angina and ventricular tachycardia with normal coronary arteries.

A 38-year-old black woman with thyrotoxicosis, whose first symptom was angina pectoris, is described. Chest pain became progressively more frequent, and an unstable angina pattern developed. Angina attacks were associated with transient ischemic electrocardiographic changes and recurrent ventricular tachycardia was documented. Coronary angiography revealed no significant obstructive lesions. The patient became free of pain with antithyroid treatment and angina has not recurred.It is important to recognize that angina pectoris may be the major presenting symptom of thyrotoxicosis; unstable angina requires careful work-up and management including the performance of coronary angiography.

Hemoptysis, recurrent cerebrovascular accident, and emergency mitral valve replacement.

Hemoptysis in mitral stenosis may occur frequently, but massive pulmonary hemorrhage is uncommon. We describe a patient with mitral stenosis who had severe hemoptysis and required anticoagulation for recurrent embolic cerebrovascular accidents. The patient underwent successful mitral valve replacement with a Hancock bioprosthesis. There was no evidence of pulmonary bleeding following operation. This case illustrated that mitral valve operation may be performed in acutely ill patients for the relief of hemoptysis.

Clinical experience with the Kay-Shiley mitral valve prosthesis: an eleven-year follow-up study.

A total of 63 patients, who survived mitral valve replacement with the Kay--Shiley caged disc mitral valve prosthesis, were followed for 11 years by single clinic group to assess long-term results post valve replacement. Sixty-one patients (97%) received a muscle guard type Kay--Shiley prosthesis. All patients received oral anticoagulation therapy. The valvular damage was caused by rheumatic disease in 51 patients, infectious endocarditis in six patients, myxomatous degeneration in two patients, coronary artery disease in two patients, and idiopathic ruptured chordae tendineae in two patients. Late death occurred in 21 patients (33%); the 10-year actuarial survival was 65%. Twenty-six patients had at least one thromboembolic event, and the total number of thromboembolic events was 10.3 per 1000 patient months. Two patients developed prosthetic valve endocarditis. Both patients were heroin addicts and died of valve ring abscess. Long-term periods of clinical observation are necessary to assess the effects and benefits of prosthetic valve implantation. These data are important for comparison with other "10-years" valves.

Coronary artery-left ventricular communications: a report of two cases and review of the literature.

Two patients with chest pain had angiographically-demonstrated communications between the three coronary arteries and the left ventricular chamber. Communications between coronary arteries and the left ventricle are unusual and communications between all three coronary arteries and the left ventricle are rare. These anomalies are, however, commonly associated with symptoms of chest pain. The presence of left ventricular hypertrophy and a widened pulse pressure may suggest a greater hemodynamic effect of the shunt flow than often suspected angiographically.

Aorta--coronary artery revascularization with an expanded polytetrafluoroethylene vascular graft. A preliminary report.

Patients requiring coronary artery surgery may have had bilateral saphenous vein stripping, and the arm veins may not be adequate for use for coronary artery grafting. The internal mammary artery may not be long enough for use for the circumflex or right coronary artery anastomoses. A suitable substitute would be most welcome for these patients or for those with marked varicosities of the saphenous vein. Five patients received expanded polytetrafluoroethylene (PTFE) grafts (Gore-Tex vascular grafts) for coronary artery revascularization because veins of adequate size or length were not available at the time of operation. These five patients are alive 9 to 14 months after graft insertion. Four of the five grafts were patent at the time of restudy 3 to 6 months postoperatively. More follow-up studies for far longer periods of time will be necessary before Gore-Tex vascular grafts can be recommended as the ideal material for coronary artery bypass surgery.

Problems in ultrasonic estimates of septal thickness.

Problems related to cardiac anatomy and ultrasonic instrumentation affect the accuracy of echographic identification of endocardial echoes. A cadaver model and 13 patients were studied, with direct identification or with the aid of echographic contrast techniques, to identify accurately the endocardial echo. The study showed that (1) echographic contrast agents delineate an endocardial echo in the central portion of the ultransonic beam; (2) a specular reflector exists within the right ventricular cavity; (3) specular reflectors within the septum may give the false appearance of border-forming echoes; (4) septal thickness varies by 1 to 5 mm after the endocardial echo has been identified by the contrast agent; and (5) spurious echoes, related to a wide beam angle, can be confused with the endocardial echo. In light of these problems, three criteria were utilized for endocardial echo identification: the prominent notch in the left septal echo, the specular quality of the right septal echo, and the association of multiple myocardial echoes moving in parallel. With these criteria, the endocardial echoes in 11 of the 13 patients could be accurately identified without the use of a contrast agent. The identification of these problems should provide helpful guidelines in developing more accurate and reproducible criteria for septal thickness measurements.

Splanchnic extraction and conversion of testosterone and dihydrotestosterone in man.

The splanchnic extraction and interconversion of testosterone and dihydrotestosterone (DHT) were studied in 7 healthy men (ages 29-46 years) undergoing cardiac catheterization. During a constant infusion of [1,2-3H]testosterone and [4-14C]DHT, the arterial and hepatic vein blood samples were taken and radioactive and non-radioactive testosterone and DHT were determined. Metabolic clearance rate (MCR), splanchnic extraction (SE), splanchnic clearance (SC), extrasplanchnic clearance (ESC), transfer constant in blood (T-DHT rhoBB) and transfer constant across the liver (T-DHT rhoSB) were calculated. The MCRT was 952 +- 172 (mean +- SD) 1/day and MCRDHT was 764 +/- 67 1/day in agreement with data from non-catheterized subjects. SET was 68.8 +/- 7.1% (mean +/- SD) and SEDHT was 37.6 +/- 5.9%. SET was significantly greater than SEDHT (P less than 0.001). The calculated SCT and ESCT were 638 +/- 112 (mean +/- SD) 1/day and 314 +/- 190 1/day, respectively. SCDHT and ESCDHT were 343 +/- 95 (mean +/-SD) 1/day and 421 +/-105 1/day, suggesting that a major fraction of testosterone is metabolized in the splanchnic organs and a higher fraction of DHT is metabolized in extrasplanchnic organs. In the interconversion study, overall conversion of testosterone to DHT in blood (T-DHT rhoBB) was 4.0 +/- 0.6% (mean +/- SD). No evidence for a net appearance of DHT by either mass or specific activity analysis in hepatic vein blood was observed in any infusion leading to the conclusion that the overall contribution of testosterone to circulating DHT from the liver (T-DHTrhoSB) was undetectable. This work indicates that conversion of testosterone to DHT occurs entirely in extrasplanchnic tissue in man.

Cholelithiasis: a frequent complication of artificial heart valve replacement.

The results of this investigation reveal that 39 per cent of patients in a study group of 46 patients with heart valve prostheses had gallstones if they survived 18 months or longer following valve replacement. In contrast, the prevalence of gallstones in a general population of autopsied rheumatic heart disease patients, including those who had been operated for severe valvular heart disease and had not survived for more than one month, was only 12 per cent. These findings suggest that gallstones are a frequent late complication of heart valve replacement.