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Interpretive analysis of epidemiological, clinical trials and practice pattern data for cardiovascular risk reduction in the contemporary setting of unprecedented demographic changes.Literature review and audit results of the Clinical Quality Improvement Network (CQIN).Coronary artery disease (CAD) is the largest single cause of death in Canada. CAD is age-related and the population is rapidly ageing, a combination that threatens an epidemic of future CAD events. Epidemiological data demonstrate a direct relation of CAD risk and serum cholesterol levels and no threshold cholesterol level below which there is no CAD risk. The epidemiological data also suggest CAD risk can be reduced by lowering serum cholesterol and this hypothesis has now been incontrovertibly confirmed by repeated randomized clinical trials. Most recently, reduction of all-cause mortality with cholesterol-lowering therapy in high risk subjects has also been confirmed. Despite the overwhelming trials and epidemiological evidence, CQIN effectiveness analyses reveal far from optimal risk assessment and management practices among high risk patients.Serum cholesterol is directly related to CAD risk. Reduction of cholesterol reduces CAD, and all-cause, mortality in high risk patients. There is a large window of opportunity to improve lipid-lowering practices, and patient outcomes, for the most deadly diseases in our society.

To evaluate the appropriateness of transplantation therapy for older patients with congestive heart failure (CHF).Comparative review of contemporary survival and quality of life data of CHF patients treated medically versus by transplantation.Approximately 300,000 Canadians have CHF and the incidence is increasing as the population ages; suitable donor allografts are found for about 300 CHF patients each year. Overall survival among cardiac allograft recipients, with a mean age of 48 years, is approximately 80% at two years. However, risk from all causes appears higher, and survival lower (range 40 to 78%), for transplant patients 55 years of age and older. Among medically treated patients, with mean age over 60 years, survival is inversely related to level of functional disability, averaging more than 90% at two years for patients with mild limitation and decreasing to 75% and 40% for patients with moderate and severe symptoms, respectively. Perceived quality of life is low in all CHF patients, but is significantly improved by intense out-patient care and education, irrespective of medical or transplant allocation.Among adults with CHF, the greatest benefit of transplantation is enhanced survival in younger severely disabled patients. However, noncardiac risks are substantial, particularly for older recipients. The great discrepancy between donor and candidate availability prohibits transplantation from being a life expanding therapy for the whole CHF population. When physicians are, simultaneously, patients' and society's advocates a utilitarian decision model using the totality of efficacy data, including degree of efficacy and population effectiveness, may assist determination of the most appropriate therapy.

To offer an attributive opinion of recent improvements in acute myocardial infarction (AMI) practice patterns and patient outcomes in the culture of an active health care research program.Review of original clinical data from five sequential, consecutively enrolled, AMI patient cohorts at the University of Alberta Hospitals from 1987-93.Early cohorts had low use of trial-proven efficacious therapies for AMI, particularly among high risk older and female patients. Over time, there were continuous and marked increases in the use of efficacious therapies and decreased use of nonefficacious therapies, with a parallel decrease in mortality among high risk patients.In a large tertiary care hospital between 1987 and 1993 the use of evidence-based AMI therapy and survival in high risk patients significantly increased. The continuity and large size of these improvements in AMI practice patterns, compared with similar populations reported in the contemporary literature, suggest it is unlikely they were due to chance. Rather, intercurrent repeated measurement and reporting of key health care performance indicators, and initiation of explicit critical path AMI practice guidelines provide a more likely explanation. Future studies by a network of community and university investigators will test whether these findings are true for a broad AMI population and whether similar practice definition and improvement tools are effective for other cardiac problems, including the management of congestive heart failure.

In animal models, dichloroacetate (DCA) facilitates recovery from severe myocardial ischemia by stimulating glucose oxidation.To evaluate the acute efficacy of DCA as a metabolic anti-ischemic intervention in patients with coronary artery disease (CAD) and exercise-induced myocardial ischemia in a clinical trial.Double-blind, randomized, crossover comparison of single dose (50 mg/kg intravenously) DCA versus placebo on clinical and electrocardiographic variables in seven patients with single vessel CAD and 34 patients with multiple vessel CAD during standard dynamic exercise testing.Blood pressure did not differ with placebo or DCA but mean heart rate was higher with DCA at rest (62 versus 59, P0.004) and at 5 mins of recovery (78 versus 75, P0.02). Exercise duration averaged 538 s with DCA and 534 s with placebo (not significant). Chest pain occurred in 14 patients in both tests, clinical ST depression occurred, in 34 placebo tests and 37 DCA tests (not significant). Body surface potential maps (BSPM) of the decrease in the area under the ST curve from rest to peak exercise averaged -5096 microV's with DCA and -5159 microV's with placebo (not significant). BSPM at 1 and 5 mins postexercise also showed no differences in rate of ST integral recovery.In the transient regional model of human myocardial ischemia induced by dynamic exercise, the acute administration of the pyruvate dehydrogenase agonist DCA was not associated with clinical or electrocardiographic moderation of, nor accelerated recovery from, ischemia. Whether DCA or metabolically similar agents that enhance oxidative metabolism are beneficial in other ischemic settings, such as the no-flow states of acute ST elevation myocardial infarction or angioplasty, requires further systematic evaluation.

To review the changing clinical profile of isolated coronary artery bypass graft (CABG) surgery patients at the University of Alberta Hospitals during the past two decades.Data were obtained retrospectively by review of patients' hospital charts and cardiologists' charts. The three patient cohorts consisted of the first 411 consecutive patients who underwent isolated CABG surgery between 1970 and 1974, 302 consecutive patients who had CABG surgery in 1984 and 346 consecutive patients who had the operation in 1989.Patients who underwent CABG surgery in 1984 and 1989 were older than patients undergoing the same operation in the 1970s. Emergency and/or urgent operations and the number of patients with prior myocardial infarct were increased significantly in 1984 and 1989. The incidence of patients with multiple vessel disease and left main stem stenosis increased significantly over the two decades. The number of bypass grafts per patient and the use of internal mammary grafts have increased since 1970. The endarterectomy procedure was performed less frequently in 1984 and 1989. The use of radial artery grafts has been discontinued. Perioperative mortality remained stable throughout the study period despite an increasing incidence of high risk patients. The major cause of death was pump failure. The incidence of peripostoperative myocardial infarct was higher in the 1970s. A multivariate analysis of the 1984 and 1989 cohorts was performed to identify temporal trends in risk factors. Emergency surgery, preoperative heart failure, age (older than 65 years), prior CABG surgery and preoperative renal failure are significant predictors of operative motility.The clinical profile of patients for isolated CABG surgery has changed over the years. The mortality rate has been stable over two decades despite the advancement of medical and surgical practices, representing a balance of increasingly high risk patients presenting for CABG surgery.

This study reviews the short and long term outcomes of patients who underwent isolated mitral valve replacement at the University of Alberta Hospitals during the past decade.Data were obtained retrospectively by review of patients' hospital charts, cardiologists' follow-up charts, contact with patients' physicians, and direct telephone or mail contact with patients and/or their surviving relatives.The clinical outcomes of 198 consecutive patients (124 women and 74 men) who underwent isolated mitral valve replacement from January 1981 to December 1990 at the University of Alberta Hospital were reviewed. Overall early operative mortality was 11%. Deaths were mainly related to pump failure and previous mitral valve replacement. Late mortality was 17%. Follow-up data were available except in five patients. Average follow-up was 6.3 years. Overall cumulative survival was 72.9 +/- 3.4% at five years and 63.1 +/- 4.8% at 10 years. The cumulative freedom from complications was 64.3 +/- 3.9% and 36.4 +/- 4.9% at five and 10 years, respectively. Long term survival rates obtained after isolated mitral valve replacement are higher than those reported in series of medically treated patients with mitral valve disease.Mitral valve replacement can prolong survival as well as improve symptoms in patients with symptomatic mitral valve disease.

The purpose of this study was to define temporally phosphorus metabolism and pH in the gastrocnemius muscles of 21 normal adult subjects during rest, dynamic exercise to exhaustion, and early and late recovery.In vivo nuclear magnetic resonance spectroscopy.At rest, the ratio of phosphocreatine to the alpha peak of ATP averaged 2.26 +/- 0.25, the inorganic phosphate to ATP ratio averaged 0.31 +/- 0.08 and pH averaged 7.10 +/- 0.04. The phosphorus metabolites exhibited immediate and progressive changes with exercise, reaching their minimum (phosphocreatine, 0.95 +/- 0.41) or maximum (inorganic phosphate, 1.95 +/- 0.75) values at exhaustion, after an average exercise of 11 +/- 4 mins. In contrast, pH changed slowly during early exercise, but fell abruptly thereafter and averaged 6.76 +/- 0.17 at exhaustion. Phosphocreatine and inorganic phosphate began to return rapidly towards preexercise values immediately on cessation of exercise. However, pH declined further in the period immediately following cessation of exercise, reaching a nadir of 6.56 +/- 0.24 an average of 2 mins into recovery. Exercise duration did not correlate highly with any metabolic variable.The data support the concept that the metabolic physiology underlying physical exhaustion of dynamic exercising muscle is multifactorial. The post exercise drop in pH also suggests that normal subjects have a greater contribution to high energy phosphate production from glycolysis, as opposed to oxidative metabolism, in early recovery.

In vivo nuclear magnetic resonance (NMR) spectroscopy was used to define several intracellular high energy phosphate variables of the gastrocnemius muscle of normal subjects during rest, graded plantar flexion exercise to exhaustion, and recovery. There were nine males and eight females with an average age of 34 +/- 8 years. At rest, pH averaged 7.09 +/- 0.03 and the energy cost index (ECI)--the ratio of inorganic phosphate to phosphocreatine--averaged 0.13 +/- 0.03. At peak exercise, the ECI increased markedly to 2.71 +/- 2.0 (P less than 0.001) and pH fell precipitately to 6.76 +/- 0.17 (P less than 0.001), indicating the high intensity of the exercise. Exercise endurance averaged 12 +/- 5 mins; it was not highly correlated with sex, age (r = 0.35), rest pH (r = 0.26), rest ECI (r = 0.38), peak exercise pH (r = 0.23) or peak exercise ECI (r = 0.38), nor exercise changes in pH (r = 0.17) and ECI (r = 0.28). At 23 mins post exercise all variables were similar to rest. Rest pH was the only variable different between males (7.10 +/- 0.03) and females (7.07 +/- 0.03) (P less than 0.05). Thus, dynamic exercise of large skeletal muscles in normal subjects was characterized by marked temporal changes in high energy phosphate profiles and very low pH at exhaustion. No single metabolic variable correlated highly with exercise endurance, suggesting that the intracellular pathophysiology of exhaustive muscle exercise and clinical fatigue may be multifactorial.

The in-hospital management and risk of death of 101 patients 70 years of age or older with acute myocardial infarction in 1987 (group 1) were compared with management and risk for 106 temporally matched patients less than 70 years old (group 2). In group 1, 49% had histories of previous myocardial infarction, compared to 25% in group 2 (P less than 0.001), and 23% of group 1 presented without cardiac pain, versus 7% of group 2 (P less than 0.001). Among the younger patients, other conventional risk factors were, in contrast, more common (Q wave infarction 84% in group 2 versus 70% in group 1; P less than 0.05) or higher (peak creatine kinase values 2222 iu/L in group 2 versus 1366 iu/L in group 1; P less than 0.001). Prior to infarction, all cardiac drugs were used more frequently in the older group 1 patients, whereas post infarction thrombolysis, beta-blockers and acetylsalicylic acid use were all more common (P less than 0.01 to P less than 0.001) in the younger group 2 patients. Post infarction exercise testing, left ventricular ejection fraction calculations and coronary angiography were all performed less frequently in group 1 (P less than 0.001). The in-hospital mortality was 35% for group 1 versus 7% for group 2 (P less than 0.001). Among all 207 study subjects, multiple logistic regression revealed thrombolysis, absence of cardiac pain, and age 70 years or older to be associated with the greatest relative mortality risk. Increased relative risk to a lesser degree was associated with previous infarction, male sex and post infarction use of antiarrhythmic medication.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical and angiographic variables of 26 coronary artery disease patients at the University of Alberta Hospitals requiring emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) were reviewed. Emergency CABG was judged necessary in 2% of 1300 consecutive patients undergoing PTCA. The most frequent indication for an emergency operation was dissection and acute closure of eccentric bend point target lesions associated with clinically severe, unremitting chest pain and ST-T abnormalities suggestive of impending myocardial infarction. The mortality rate for the combined procedures of failed PTCA and CABG was low (3.8%). The incidence of periprocedural infarction was high (61%); it was, however, associated with a benign clinical course and electrocardiographic evidence of significant reversibility of acute phase damage. Thus, overall, emergency CABG appears to be a clinically efficacious treatment for patients with threatened or impending infarction as a consequence of failed PTCA.