Coronary artery disease and its management: influence on survival in patients undergoing aortic valve replacement.

Data from 1,156 patients greater than or equal to 30 years of age who underwent aortic valve replacement alone or with coronary artery bypass grafting from 1967 through 1976 (early series) and 227 similar patients operated on during 1982 and 1983 (late series) were reviewed. In the early series, 414 patients (36%) had preoperative coronary arteriography (group 1): group 1A (n = 224) did not have coronary artery disease, group 1B (n = 78) had coronary artery disease but did not undergo bypass grafting and group 1C (n = 112) had coronary artery disease and underwent bypass grafting. The 742 patients in group 2 did not have preoperative arteriography. Operative mortality rates (30 day) in groups 1A, 1B, 1C and 2 were 4.5, 10.3, 6.3 and 6.3%, respectively (p = NS). The 10 year survival in both groups 1 and 2 was 54%; in groups 1A, 1B and 1C it was 63, 36 and 49%, respectively (1A and 1B, p less than 0.01). In the late series, the 227 patients were divided into similar groups (group 1A, n = 73; 1B, n = 32; 1C, n = 99), and 90% had preoperative coronary arteriography. Operative mortality rates (30 day) for groups 1A, 1B and 1C were 1.4, 9.4 and 4.0%, respectively; that for group 2 (no preoperative arteriography, n = 23) was 4.3%. Definition of coronary anatomy by angiography seems important in most patients greater than or equal to 50 years old who are candidates for aortic valve replacement, and bypass grafting is recommended for those with significant coronary artery disease.

Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis.

Acetylcholine receptor (AChR) binding and AChR modulating antibodies were found with approximately the same frequency (86%) in 349 patients with myasthenia gravis (MG). However, the total yield of positive serological results was significantly improved (90%) by assaying AChR modulating antibodies when AChR binding antibodies were not detected, because in 27 patients (8%) only one of the two tests was positive. The immunoprecipitation test for AChR blocking antibodies yielded fewer positive results (52%), but there was a significant correlation between the degree of AChR blockade and generalization of muscle weakness. In no patient was this the only positive test, because the test for AChR modulating antibodies in this study detected both AChR blocking and modulating antibodies. Human muscle AChR was used as antigen in all tests. False positive results were rare and were attributed to unexplained antibodies to 125I-alpha-Bgt (AChR binding antibody assay) and recent general anesthesia using muscle relaxants (AChR blocking and AChR modulating antibody assays). Unexplained positive results, documented previously in 5% of patients with the Lambert-Eaton myasthenic syndrome and amyotrophic lateral sclerosis (ALS), were found in this study in two of 22 patients with ALS, but in none of 427 patients with miscellaneous neurological diseases. Patients with severe generalized MG and/or thymoma tended to have higher titers of AChR binding antibodies and greater AChR modulating antibody activity. However, some patients with severe muscle weakness had low titers of antibodies, and some patients in remission or with only ocular manifestations had high titers. These seemingly paradoxical results reflect heterogeneity in the specificities, affinities, and isotypes of anti-AChR antibodies. To effect pathogenicity, antibodies must have access in vivo to extracellular antigenic sites on the AChR. One would anticipate that antibodies with greatest pathophysiological potential would be of an IgG with greatest pathophysiological potential would be of an IgG subclass that activates complement, or of a specificity that competes for acetylcholine's binding site on the receptor or readily cross-links two AChR molecules to trigger receptor modulation (e.g., by binding to sites on the duplicated alpha-subunit). In patients with suspected MG who lack serological evidence of anti-AChR antibodies, motor endplate biopsy is required for microelectrophysiological, immunochemical, and ultrastructural studies to establish with certainty whether or not the condition is acquired MG.

Coronary heart disease in residents of Rochester, Minnesota. VII. Incidence, 1950 through 1982.

An epidemiologic study of coronary heart disease in residents of Rochester, Minnesota, has been updated through 1982. Between the time that mortality rates began to decline in the late 1960s and now, the age-adjusted incidence of all types of coronary heart disease in residents of Rochester decreased 11% in men but increased 9% in women. This difference was due mainly to changes in the incidence of myocardial infarction as the initial manifestation of coronary heart disease-in men, the rates declined by 20%, whereas the rates for women increased by 17%. The greatest changes were in the age group 50 to 69 years. From the 1965 through 1969 period to the 1979 through 1982 period, the age-adjusted incidence of sudden unexpected death as the initial manifestation of coronary heart disease decreased in both sexes, but the incidence of angina pectoris increased in both men and women. The 24-hour and 30-day case fatality rates for myocardial infarction and the incidence rates for sudden unexpected death have stabilized. Additional studies are needed to identify the reasons for the striking divergence in secular trends in coronary heart disease for men as compared with those for women.

The epidemiology of sarcoidosis in Rochester, Minnesota: a population-based study of incidence and survival.

Using the unique data resources of the Rochester Epidemiology Project, a community-based study of clinically diagnosed sarcoidosis was conducted. In this population-based study, the 75 Rochester, Minnesota, residents with sarcoidosis initially diagnosed between 1946 and 1975 (incidence cohort) were followed through their comprehensive medical records in the community to January 1, 1982. The age- and sex-adjusted incidence of sarcoidosis was 6.1 per 100,000 person-years. The age-adjusted incidence of sarcoidosis was similar in males (5.9) and females (6.3), with a peak incidence in males 30 to 39 years old (18.7) and in females 40 to 49 years old (15.6). A secular increase in sarcoidosis incidence was noted in the period 1946-1975 for females, with a marked increase in the number and percentage of biopsy-documented cases. Seasonal variation in sarcoidosis incidence was minimal, with a seasonal peak of 31% of the Rochester cases being diagnosed during the spring (March-May). Survival, compared with that of the North Central United States, was unimpaired in this sarcoidosis incidence cohort.

Coronary heart disease in residents of Rochester, Minnesota. VI. Hospital and posthospital course of patients with transmural and subendocardial myocardial infarction.

During the period 1960 through 1979, 1,221 residents of Rochester, Minnesota, who were 30 years of age or older had a myocardial infarction as the first manifestation of coronary heart disease. Patients who had a prior diagnosis of congestive heart failure or valvular heart disease were excluded from this study. Of the 1,221 patients, 784 had a transmural infarction, 353 had a subendocardial infarction, and 84 had infarctions that could not be classified (most of the unclassified infarctions were associated with sudden death in patients who were not hospitalized). The age- and sex-adjusted 30-day case fatality rate was 18% among those with transmural and 9% among those with subendocardial myocardial infarction. No significant difference was found in subsequent survivorship or in net survivorship free of reinfarction during the first 5 years of follow-up. Five-year net survivorship free of reinfarction, coronary artery bypass operation, and cardiac death was not significantly different between the two groups, nor was net survivorship free of five established events (the three aforementioned events plus the development of congestive heart failure or angina). When these five events were considered independently in the two infarction cohorts, however, development of congestive heart failure was more common among patients with transmural infarction (P less than 0.01), whereas the development of angina was more common among patients with subendocardial myocardial infarction (P less than or equal to 0.06).

Coronary heart disease in residents of Rochester, Minnesota. V. Prognosis of patients with coronary heart disease based on initial manifestation.

During the period 1960 through 1979, 1,014 residents of Rochester, Minnesota, had a diagnosis of classic angina pectoris as the first manifestation of coronary heart disease, and 1,013 had a myocardial infarction as the initial manifestation. In the angina cohort, about 50% were men, and of them, 20% were 70 years old or older. The female patients were an average of 6 years older than the men, and 43% were 70 years old or older. In this cohort, the 5-year survival rate increased from 77% in the 1960s to 87% in the 1970s (P less than 0.01). The 5-year net survivorship free of a myocardial infarction increased from 76% to 85% during that same time (P less than 0.01). In the myocardial infarction cohort, the 5-year death rate among the 30-day survivors of myocardial infarction was the same during both decades of the study. The age-adjusted reinfarction rate per 100 person-years at risk during teh first 5 years of follow-up decreased very slightly among men and increased among women; thus, it remained essentially unchanged overall. Although the case fatality rate in the myocardial infarction cohort declined sharply from the 1960s to the 1970s, the long-term prognosis of the 30-day survivors of a myocardial infarction did not improve.

Follow-up clinical results in patients undergoing percutaneous transluminal coronary angioplasty.

Complete follow-up data were obtained from 229 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1979 and 1982 (mean follow-up 14 months, range 6 to 37). Single-vessel disease was present in 143 and multivessel disease in 86. PTCA was successful in 153 patients (67%). Failure was followed initially by bypass surgery in 59 and by continued medical therapy in 17. After successful PTCA, 90% of patients were improved subjectively and 74% were asymptomatic at follow-up. After unsuccessful PTCA but prompt bypass, 90% were improved subjectively and 85% were asymptomatic. Among the 229 patients, 39 (17%) required an additional intervention because of angina during follow-up; 15 of these had repeat PTCA and 18 had bypass surgery. Among patients with successful PTCA, revascularization was complete in 77% and partial in 23%. The completeness of revascularization with PTCA had a significant impact on follow-up. The follow-up data of patients with successful single-vessel PTCA and of those with multivessel disease with complete revascularization were similar. When the patients with complete revascularization were compared with those with multivessel disease but incomplete revascularization, the follow-up data were characterized by a higher incidence of angina or need for bypass surgery in the latter group (63%) than in the former group (29%); those with incomplete revascularization also had a significantly reduced event-free survival.

Mitral regurgitation due to ruptured chordae tendineae. Early and late results of valve repair.

From 1958 through 1980, 131 patients had repair of ruptured chordae tendineae of the mitral valve; 62% were men. Ages ranged from 5 to 70 years (median 57). Chordae to the anterior mitral leaflet were ruptured in 44 patients (34%), to the posterior mitral leaflet in 85 (65%), and to both leaflets in two patients (1%). The mitral valve was repaired by leaflet plication without resection in 116 patients, plication after wedge resection of the unsupported leaflet in six, Ivalon sponge buttress of the posterior leaflet in three, resuspension of chordae in two, and annuloplasty alone in the remaining four. Mitral valve annuloplasty was performed in addition to leaflet repair in 115 patients (88%). Operative (less than 30 days) mortality was 6.1%. Survival rate of patients dismissed from the hospital was 92% at 5 years and 73% at 10 years. There were no differences in late survival or risk of reoperation for recurrent or residual mitral insufficiency between patients with ruptured chordae to the anterior leaflet and those with ruptured chordae to the posterior leaflet. Survival was significantly better for the group with repair than it was for a group that underwent mitral valve replacement for ruptured chordae during this same time interval (5 year survival rate, 92% versus 72%, p less than 0.003). The incidence of thromboembolism after repair was 1.8 episodes/100 patient-years compared with 8.0 episodes/100 patient-years after replacement. Our data indicate that valvuloplasty is the procedure of choice for most patients with mitral regurgitation owing to ruptured chordae tendineae, including selected patients with ruptured chordae to the anterior leaflet.

Epidemiology of systemic lupus erythematosus and other connective tissue diseases in Rochester, Minnesota, 1950 through 1979.

The incidence and prevalence rates of connective tissue disease syndromes in Rochester, Minnesota, from 1950 through 1979 are reported. The incidence of definite systemic lupus erythematosus (SLE) has not increased since 1960. The incidence of SLE in the elderly population was higher than that in previous reports. Rates of SLE and discoid lupus erythematosus were approximately equal. Other diagnoses (in decreasing order of frequency) were suspected lupus erythematosus, scleroderma, drug-induced lupus, and overlapping connective tissue disease syndromes. The 10-year survival of patients with definite SLE was decreased, and the survival of patients with suspected SLE was the same as that of the general population.

The angiographic spectrum of coronary artery disease.

A wide spectrum of coronary arteriographic anatomic findings exists in patients presenting with clinically stable and unstable angina pectoris. Although some generalizations about the clinical-angiographic correlations can be made, we are continuously reminded of the frequent individual patient whose findings fall well outside of these generalizations. The majority of patients will have double- or triple-vessel coronary disease, with approximately 10 percent having in addition a left main coronary artery stenosis of at least 50 percent luminal diameter narrowing. Patients with unstable angina tend to have slightly greater vessel involvement in terms of lesion severity, though major differences, in general, are not seen. Intracoronary thrombus is present more frequently in patients with unstable angina and in those with recent myocardial infarction, though the overall incidence of this finding is low. Knowledge of the anatomic extent of coronary atherosclerosis is useful for determining prognosis and for selection from an ever-increasing variety of medical and surgical treatment options. Cardiac imaging is a continuously evolving field with new techniques such as digital angiography, three-dimensional dynamic imaging (dynamic spatial reconstructor), and nuclear magnetic resonance undergoing preclinical or clinical evaluation. These modalities hold promise for ultimately evaluating the coronary vessels from unlimited angles, assessing regional transmural myocardial perfusion and the cellular metabolic consequences of ischemia. However, current therapies (bypass surgery or coronary angioplasty) are based upon modifications of major epicardial coronary anatomy, and techniques that adequately define this anatomy are required. Moreover, for imaging data to have prognostic application, it must have previously established clinical prognostic correlates and be broadly applicable or widely available for patients. Thus for the present and immediate foreseeable future, coronary angiography will be the primary method for establishing the anatomic abnormalities of the coronary arteries, and these angiographic studies will remain vital for the clinical management of ischemic heart disease.

Cold pressor test as a predictor of hypertension.

To determine the usefulness of the cold pressor test as a predictor of hypertension, we compared the blood pressure recordings available from 142 patients in 1979 with readings obtained during performance of two cold pressor tests, the first in 1934 when these subjects were children, and the second in 1961. Forty-eight subjects were hyperreactors to the tests in either 1934 or 1961, and 94 were normoreactors. At last follow-up, blood pressures in 14 of the hyperreactors were between 140 and 160 mm Hg systolic or 90 and 100 mm Hg diastolic (Stratum 1) and in 20 exceeded 160 mm Hg systolic or 100 mm Hg diastolic (Stratum 2). Ten normoreactors had casual blood pressures in Stratum 1 and eight in Stratum 2. Hypertension had thus occurred in 71% of the hyperreactors and 19% of the normoreactors. Fifteen hyperreactors were receiving antihypertensive therapy, and this reduced the severity of the casual blood pressure elevation in most patients to Stratum 1. Antihypertensive therapy had been started in three normoreactors. The duration of follow-up, 45 years, and the mean age at follow-up, almost 57 years, were greater in this study than in any previously reported study. Early hyperreactivity was related to future hypertension in enough subjects to suggest that an abnormal response to an external cold stimulus may be useful as an indicator of future hypertension.

Aortic and mitral valve incompetence: long-term follow-up (10 to 19 years) of patients treated with the Starr-Edwards prosthesis.

The long-term course (mean 15 years) of 336 patients with valvular incompetence who underwent Starr-Edwards ball valve implantation between 1962 and 1971 was reviewed. Eighteen patients (10%) with aortic valve replacement and 24 (16%) with mitral valve replacement died early postoperatively. Mortality remained high (31%) in the first 3 years after aortic valve replacement; it was highest (13%) in the first year after mitral valve replacement and then approached the normal rate. The most common mode of death was sudden death after aortic and cardiac failure after mitral valve replacement. At follow-up, 76% of survivors had improved symptomatically. Three instances of primary valve malfunction occurred. The probability of freedom from thromboembolism at 15 years postoperatively was 56% for aortic valve replacement and 52% for mitral valve replacement. The Starr-Edwards valve prosthesis is durable over prolonged follow-up period, but thromboembolism remains a persistent problem. Survival may be normal for patients surviving the early postoperative years.

Coronary heart disease in residents of Rochester, Minnesota. IV. Prognostic value of the resting electrocardiogram at the time of initial diagnosis of angina pectoris.

The data in this study were based on the 1,154 Rochester residents in whom a resting electrocardiogram had been obtained at the time of diagnosis of angina pectoris as the initial manifestation of coronary heart disease during the 26-year period 1950 through 1975. The finding of a normal electrocardiogram at the time of the initial diagnosis of angina pectoris was associated with a good prognosis. Survival at 5 years was equal to that expected, for the given age and sex distribution, under a cohort life table for the Minnesota white population. In contrast, in those patients who had an abnormal electrocardiogram at the time of diagnosis, the observed survival rate was 86% of that expected at 5 years.

ALS and heavy metals: a pilot case-control study.

We conducted a case-control study of suspected risk factors for ALS among referral patients seen at the Mayo Clinic. Responses to questions about demographic factors, diet, medical history, travel, infectious disease, and other variables were similar in ALS patients and controls. In all but a few items, the responses of the cases and controls did not differ significantly. A significant level of shared exposure to an exogenous agent or environmental insult among cases was noted mainly for heavy metals.

Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations.

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.

The dichotomy of myocardial and cerebral infarction.

The Mayo Clinic medical record linkage and indexing system was used to examine changes in incidence and case fatality of myocardial infarction (MI), sudden unexpected death (SUD), and cerebral infarction (CI). The average annual age and sex adjusted incidence rates for MI (including SUD) and CI declined by 14% and 55%, respectively, between 1950-54 and 1975-79. The decline in the incidence of MI was due to a reduction in sudden unexpected death (SUD), greatest in younger persons. 30-day case fatality after MI declined from 50% to 35% during this period.

Employment and recreation patterns in patients treated by percutaneous transluminal coronary angioplasty: a multicenter study.

Employment and recreational patterns were analyzed in 279 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) for treatment of symptomatic coronary artery disease. PTCA was successful in 180 patients (65%). When it was unsuccessful, coronary artery bypass graft surgery was usually performed (80%). Return-to-work rates were high irrespective of the outcome of PTCA. Of patients employed full-time or part-time before treatment, 98.5% of those who had successful PTCA alone and 97% of those whose PTCA was unsuccessful but who underwent uncomplicated coronary artery bypass surgery maintained or improved their work status. In a subgroup of men who had been employed in occupations requiring physical labor, 85% of the men whose PTCA was successful returned to work, compared with 68% of those whose PTCA was unsuccessful. The interval from attempted PTCA to return to work was significantly shorter in the successfully treated group; in patients with successful PTCA, the median time to return to work was 14 days, compared with 60 days in patients in whom PTCA was unsuccessful (p less than 0.001). During follow-up, patients with successful PTCA had less angina and were more active in recreational activities than patients who required alternative treatments.

Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole.

Despite the use of oral anticoagulation in patients with prosthetic heart valves, persistent thromboembolism over time warrants a search for improved methods of prevention. Thus, patients receiving 1 or more mechanical prosthetic heart valves were randomized to therapy with warfarin plus dipyridamole (400 mg/day) or warfarin plus aspirin (500 mg/day) on the basis of location and type of valve and surgeon, and followed up with a concurrent, nonrandomized control group taking warfarin alone. In 534 patients followed up 1,319 patient-years, excessive bleeding (necessitating blood transfusion or hospitalization) was noted in the warfarin plus aspirin group (23 of 170 [14%], or 6.0/100 patient-years) compared with warfarin plus dipyridamole (7 of 181 [4%], or 1.6/100 patient-years, p less than 0.001), or warfarin alone (9 of 183 [5%], or 1.8/100 patient-years, p less than 0.001). A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group (2 of 181 [1%], or 0.5/100 patient-years) as compared with warfarin plus aspirin (7 of 170 [4%], or 1.8/100 patient-years), or warfarin alone (6 of 183 [4%], or 1.2/100 patient-years). Adequacy of anticoagulation (based on 12,720 prothrombin time determinations) was similar in all 3 groups with 65% of prothrombin times in the therapeutic range (1.5 less than or equal to prothrombin time/control less than or equal to 2.5), 30% too low, and 5% too high. Warfarin plus aspirin therapy resulted in excessive bleeding and is contraindicated. Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected.

Coronary heart disease in residents of Rochester, Minnesota, 1950-1975. III. Effect of hypertension and its treatment on survival of patients with coronary artery disease.

The data in this blood pressure study were obtained from 1,069 patients who had their first manifestation of coronary artery disease during the 16-year period 1960 through 1975. Case fatality rates (death within 30 days) were least in the normotensive and treated hypertensive patients with myocardial infarction and greatest in the untreated hypertensive patients. Women were less likely than men to acquire coronary artery disease, but a higher proportion of women with coronary artery disease had hypertension. Patients with definite hypertension were older than those with borderline hypertension, and patients with borderline hypertension were older than normotensive patients with coronary artery disease. The data demonstrate that hypertension is a prognostic factor of serious significance in patients who have symptomatic coronary artery disease, and the prognostic significance of borderline hypertension is almost as serious as that of definite hypertension in these patients. Treatment improved survival in patients with definite hypertension, and adequate treatment improved survival to a greater degree than did inadequate treatment.