Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Use of nonprescription medications by patients with congestive heart failure.

OBJECTIVE: To define the utilization pattern of nonprescription therapies in patients with congestive heart failure (CHF) and to compare this pattern with that of an age- and gender-matched control group without any self-reported heart conditions. DESIGN: Survey questionnaire completed by participants at home. SETTING: Ambulatory CHF clinic in a tertiary care hospital. SUBJECTS: Patients attending the clinic between July 1995 and May 1996 who agreed to participate. Control subjects were age- and gender-matched participants identified and approached by participating patients. OUTCOME MEASURES: Nonprescription therapies used at least once weekly. RESULTS: Completed questionnaires were received from 180 (75%) of the 239 patients who agreed to participate and from 133 controls. Mean age of responding patients was 69 years (63% men). Controls were younger, with a mean age of 64 years (63% men). The most commonly used nonprescription medication categories for both patients and controls, with no significant intergroup differences, were vitamins and minerals (59% patients, 50% controls), pain relievers (48% and 43%, respectively), herbal or health food products (38% and 38%), antacids (26% and 28%), and laxatives (24% and 21%). Significantly fewer patients than controls used cough and cold products (9% vs. 17%; p < 0.05), specifically oral decongestants (0.6% vs. 5%; p < 0.01), and more patients than controls used nutritional supplements (17% vs. 4%; p < 0.01). CONCLUSIONS: Overall, use of nonprescription therapies by our CHF clinic patients is similar to that of an age- and gender-matched population without a self-reported heart condition. The differences in medication use observed between patients and controls included cough and cold products that might be harmful. This likely reflects appropriate caution with which CHF patients approach nonprescription therapies.

Insights into the contemporary epidemiology and outpatient management of congestive heart failure.

OBJECTIVES: To evaluate the epidemiology, prognosis, and patterns of practice in patients with chronic congestive heart failure (CHF) treated and followed at a specialized clinic. METHODS: Prospective cohort study of consecutive patients referred to and followed up in a specialized heart failure clinic between September 1989 and March 1996. RESULTS: Of the 628 patients referred, 566 were confirmed to have CHF. Mean duration of follow-up was 518 +/- 490 days (range 1 to 2192 days). Vital status was available for 99.3% of patients. Mean age at enrollment was 66 years, 68% were men, 67% had an ischemic cause of heart disease, and 78% had systolic dysfunction. Patients with preserved systolic function were older, more often female, had higher mean systolic blood pressures, and a lower prevalence of ischemic heart disease, ventricular arrhythmias, or impaired renal function when compared with those with systolic dysfunction (all P

The treatment and prevention of coronary heart disease in Canada: do older patients receive efficacious therapies? The Clinical Quality Improvement Network (CQIN) Investigators.

OBJECTIVES: To review the evidence for clinical efficacy and cost-effectiveness of proven medications in the treatment and prevention of myocardial infarction (MI) in older patients; to summarize Canadian data on treatment patterns and clinical outcomes for younger and older patients with coronary heart disease; to explore the reasons for gaps between best care, based on the evidence of efficacy from trials, and usual care, based on the population effectiveness audits; and to explore potential approaches to closing the care gaps. DESIGN: Review of the recent clinical trial literature on the management of MI, highlighting results in older patients. Review of medication utilization and outcomes data from a series of large, consecutively enrolled patient cohorts with acute MI (N = 7070) in a variety of cardiac care settings (10 centers in five Canadian provinces, including university-based teaching hospitals, community hospitals, cardiologist and family physician out-patient clinics) from 1987 to 1996. RESULTS: There is no qualitative interaction of cardiac therapies: thrombolytics, beta-blockers, acetylsalicylic acid (ASA), and statins are efficacious in all clinically relevant patient subgroups, including older people. However, there are consistent gaps between usual care and best care, particularly among older patients (in whom there is also a concomitantly higher mortality risk). Repeated multivariate analyses confirm older age to be an independent contributor to increased risk. Use of efficacious medications is, in contrast, consistently associated with increased survival. Analysis of temporal trends suggests beneficial changes in practice patterns and outcomes are possible to achieve. However, "best care" has not been rapidly or completely achieved. Review of strategies to close these care gaps suggests that audit and feedback, critical pathways, and multifactorial interventions involving patients and other members of the healthcare team as well as physicians may be the most efficacious strategies for change. CONCLUSIONS: Despite equal or enhanced efficacy, there is consistently less prescription of proven drugs among older cardiac patients. These care patterns may contribute to their enhanced risk. The causes underlying these practice patterns are complex, and their population impact may be undervalued by clinicians and managers. Improvement of these patterns is difficult, but ultimately it would be beneficial for this presently disadvantaged, readily identified, high risk patient population.

Contemporary practice patterns in the management of newly diagnosed hypertension.

OBJECTIVE: To determine what proportion of patients with hypertension are managed in accordance with guidelines established by the Canadian Hypertension Society. DESIGN: Retrospective medical record review. SETTING: Outpatients seen in primary care offices and internal medicine referral clinics in Edmonton. PATIENTS: All 969 adults who presented with a new diagnosis of essential hypertension from Sept. 1, 1993, to Dec. 31, 1995. OUTCOME MEASURES: Initial laboratory tests performed, advice concerning nonpharmacologic treatment given, antihypertensive drugs prescribed and any contraindications to thiazide diuretics or beta-adrenergic blocking agents documented. RESULTS: The mean age of the 969 patients in the sample was 52.5 years; 129 (13%) of the patients were older than 70 years of age; and 500 (52%) were women. Most of the patients (704, 73%) had mild or moderate diastolic hypertension. In the 617 patients who underwent laboratory tests related to hypertension, the creatinine level was determined in 466 (76%), the cholesterol level in 372 (60%), a urinalysis was conducted in 378 (61%), the serum potassium level was checked in 343 (56%), the sodium level in 323 (52%) and an electrocardiogram was performed in 303 (49%). Liver function tests, which are not recommended in the guidelines, were performed in 338 patients (55%). Although there were differences in prescribing among physicians in the 711 patients given first-line therapy, most (238, 34%) were prescribed angiotensin-converting-enzyme (ACE) inhibitors. Lifestyle modification, without drug therapy, was suggested for 180 (25%) of the patients. Although the guidelines recommend their use for first-line drug therapy, only 82 patients (12%) were given beta-adrenergic blocking agents and only 75 (11%) were given thiazide diuretics. Of the patients who were prescribed an antihypertensive other than a thiazide or beta-adrenergic blocking agent as first-line drug therapy, only 161 (43%) had a documented contraindication to thiazides or beta-adrenergic blocking agents. CONCLUSIONS: There is variation in the contemporary care of patients with hypertension. Further studies are required to determine the reasons underlying physicians' noncompliance with the evidence-based guidelines established by the Canadian Hypertension Society.

A survey of clinician attitudes and management practices in hypertension.

In order to determine the compliance of Canadian physicians with evidence-based hypertension guidelines, a self-administered questionnaire survey was distributed to a stratified random sample of 473 physicians in Central Alberta, Canada in December 1995. Excluding non-deliverable questionnaires, a response rate of 67% was obtained. Twenty-five per cent of respondents routinely used the fourth Korotkoff sound to define diastolic blood pressure (DBP). Investigations recommended for the initial workup of a patient with mild hypertension included serum creatinine (90%), electrolytes (72%), glucose (50%), cholesterol (44%), electrocardiogram (65%), and urinalysis (76%). The non-pharmacologic treatment advice routinely advocated for patients with mild hypertension included salt restriction (87%), weight loss (100%), and regular aerobic exercise (92%). While 46% of respondents recommended antihypertensive therapy for an otherwise healthy patient with an average DBP of 95 mm Hg, 76% recommended therapy for patients with the same BP plus target organ damage or other cardiovascular risk factors. Medication choices varied, although angiotensin-converting enzyme inhibitors were chosen by 46% for patients with uncomplicated essential hypertension and 67% for patients with other cardiovascular risk factors, and beta-blockers were the most frequently chosen first-line agents (56%) for the patient with target organ damage. There was considerable variability in the self-reported practice patterns, and concordance was greater for those recommendations which were consistent across the currently available guidelines. Consistent with the principle underlying all of the current hypertension guidelines, respondents were more aggressive in their treatment of hypertensive patients with other cardiovascular risk factors or target organ damage.

Rationale and design features of a clinical trial examining the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). SCAT Investigators.

BACKGROUND: In the treatment of coronary atherosclerotic artery disease (CAD), the mechanisms by which lipid lowering, a proven therapy, produces beneficial clinical effects remain unclear. Moreover, although potential mechanisms of benefit are well known and increasingly applied clinically, there are no conclusive data from clinical trials studying primarily the antiischemic effects of angiotensin-converting enzyme (ACE) inhibition in patients with normal heart function. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) is designed to clarify some of these issues in CAD patients with normal or mildly elevated cholesterol. DESIGN AND OBJECTIVES: SCAT is a three- to five-year, multicentre, randomized, double-blind, placebo controlled, 2 x 2 factorial trial evaluating the effects of cholesterol lowering therapy by simvastatin and/or ACE inhibition by enalapril on anatomic coronary atherosclerosis progression assessed by quantitative coronary angiography in CAD patients with preserved left ventricular function and total cholesterol levels between 4.1 and 6.2 mmol/L. PATIENTS: Of 460 patients (age 61 +/- 9 years; 409 males, 51 females) enrolled between June 1991 and July 1995, 230 were randomized to simvastatin and 230 to placebo, and 229 to enalapril and 231 to placebo. Average baseline total cholesterol level was 5.20 +/- 0.61 mmol/L, high density lipoprotein cholesterol was 0.99 +/- 0.25 mmol/L, low density lipoprotein cholesterol was 3.36 +/- 0.57 mmol/L and triglycerides were 1.82 +/- 0.75 mmol/L. The trial will be completed in June 1998. SIGNIFICANCE: Insights gained from this long term angiographic trial will lead to a better understanding of the mechanisms of benefits of these two treatments, both alone and in combination. Of particular interest is that this trial will be able to examine a suspected beneficial interaction, if present, between these two treatments.

Quantitative relation of electrocardiographic and angiocardiographic measures of risk in patients with coronary atherosclerosis. Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) Investigators.

OBJECTIVE: To correlate angiocardiographic and electrocardiographic (ECG) measures of risk in coronary artery disease (CAD) patients. SETTING: Baseline substudy of the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT), a 2 x 2 factorial, randomized, controlled trial of CAD regression. PATIENTS: One hundred and twenty-three CAD patients, 113 males and 10 females; average age, 59 years. METHODS: Bivariate correlations of multiple quantitative measures of epicardial coronary angiographic luminal narrowing (quantitative coronary angiography [QCA]) and body surface ECG maps of the sum of the decrease in the potential time integral of the ST segment (SST decrease) between rest and symptom-limited exercise and between rest and 1 and 5 mins postexercise recovery. RESULTS: The average number of epicardial coronary segments analyzed per patient was 12. The mean diameter averaged 2.78 mm; the minimal diameter, 2.01 mm. The mean percentage coronary stenosis averaged 29.6% and the most severe averaged 62.9%. sigma ST decrease averaged -5323 microV.s between rest and peak exercise and recovered slowly, averaging -5117 microV.s at 1 min postexercise and -4562 microV.s at 5 mins. No QCA measure correlated with any ECG variable (range of r, 0.002 to -0.179; not significant). CONCLUSIONS: Among CAD patients there are no close, or causal, relations between angiographic measures of anatomic epicardial coronary atherosclerosis and ECG functional measures of exercise-induced myocardial ischemia. These data suggest that demonstrated values of stress ECG and coronary angiography for the prediction of clinical risk in CAD patients are largely independent of each other.

Cause-specific noncardiac mortality in patients with congestive heart failure--a contemporary Canadian audit. Clinical Quality Improvement Network (CQIN) Investigators.

BACKGROUND: Noncardiac mortality in congestive heart failure (CHF) is substantial. OBJECTIVE: To define the specific causes of noncardiac mortality among hospitalized CHF patients. DESIGN: Retrospective medical record audit. SETTING: Three hospitals in British Columbia and Alberta, 1992-93. PATIENTS: A total of 2216 consecutive patients admitted with CHF. MAIN RESULTS: The overall mortality rate was 404 of 2216 (18%). Cause of death was cardiac in 290 of 404 (72%) patients, with an average age of 76 years. However, 114 of 404 (28%) deaths, in patients with an average age of 69 years, had noncardiac causes. Four causes accounted for almost 70%, of the noncardiac deaths: cancer (24%); pneumonia (16%); other pulmonary diseases, including embolism (15%); and cerebrovascular disease (11%). Renal disease (9%), gastrointestinal disorders (9%), non-pulmonic sepsis (7%), multiple system failure (5%) and trauma or surgical complications (4%) accounted for most of the remaining noncardiac deaths. CONCLUSIONS: Noncardiac causes produce a substantial proportion of deaths among elderly and sick CHF patients. As the survival of patients with CHF improves, the relative risk of noncardiac mortality in this population will likely increase. However, since hospitalized CHF patients so closely reflect their general population counterparts in terms of cause-specific mortality risk, the search for an ideal therapy might be viewed as a quixotic search for the cure of death.

Nonrheumatic atrial fibrillation: a brief overview.

OBJECTIVE: To review the effectiveness of current approaches in the treatment of patients with nonrheumatic atrial fibrillation (NRAF). DESIGN: Review of the available English-language articles on the epidemiology, clinical consequences, management and prevention of stroke in patients with NRAF. RESULTS: The incidence of atrial fibrillation increases steadily in both sexes in relation to age. The clinical independent risk factors for NRAF are diabetes mellitus, hypertension, recent heart failure, valvular heart disease and myocardial infarction. The echocardiographic predictors are left atrial enlargement, reduced left ventricular function and left ventricular wall thickness. The clinical consequences of NRAF are increased risk of stroke, mortality and left ventricular dysfunction. The management of NRAF includes correction of cause, termination of acute episode, maintenance of sinus rhythm, ventricular rate control and prevention of systemic embolism. CONCLUSION: NRAF is a common cardiac arrhythmia that is associated with high incidence of mortality and systemic embolism. Anticoagulation is effective in preventing embolism with acceptable risk of major bleeding. Acetylsalicylic acid is less effective but a reasonable alternative when anticoagulation is contraindicated.

Plasma fatty acid levels in infants and adults after myocardial ischemia.

High levels of fatty acids are detrimental during reperfusion of ischemic hearts in part because of an inhibition of myocardial glucose use. We therefore measured plasma fatty acids during and after myocardial ischemia in both adult and pediatric patients. In adult patients undergoing thrombolytic therapy after an acute myocardial infarction, plasma fatty acids levels were elevated on admission to hospital (0.96 +/- 0.06 vs 0.40 +/- 0.01 mmol/L in healthy control subjects) and remained elevated throughout the initial 48 hours of hospitalization. In adult patients undergoing cardiac surgery, plasma fatty acids were markedly increased during surgery and at the time of the release of the aortic cross clamp (2.21 +/- 0.54 and 1.61 +/- 0.32 mmol/L, respectively). In children and infants (mean age 4.33 +/- 0.44 years) who had surgery to correct congenital heart defects, fatty acid levels during surgery increased to 3.27 +/- 0.26 mmol/L and remained elevated during immediate reperfusion (1.91 +/- 0.15 mmol/L) and for 24 hours after surgery (1.67 +/- 0.22 mmol/L). Because experimental studies have shown that high levels of fatty acids are detrimental to recovery of adult animal hearts, we determined the effect of high fatty acid levels on reperfusion recovery of isolated working hearts from 1-day-old rabbits perfused with 0.4 mmol/L palmitate (normal fat) or 1.2 mmol/L palmitate (high fat) and subjected to 50 minutes of global ischemia followed by aerobic reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Mortality risk and patterns of practice in 2,070 patients with acute myocardial infarction, 1987-92. Relative importance of age, sex, and medical therapy.

OBJECTIVE: To define contemporary age- and sex-related mortality risks and patterns of medical practice in acute myocardial infarction (AMI). DESIGN: Retrospective comparison of demographic and clinical variables, including the use of proven effective AMI medical therapy, among AMI patients cohorts from 1987 to 1992. PATIENTS/SETTING: Of a total of 2,070 AMI patients, 629 were women and 1,441, men; 951 patients were managed in university hospitals, 641 in a regional hospital, and 478 in community hospitals. INTERVENTIONS: No direct study interventions; results of practice patterns and risk analyses of the earlier (1987-90) AMI cohorts, however, were published concurrently with the actual practices of the more recent (1991-92) cohorts and may have had some indirect effect on the recent practice patterns. RESULTS: Univariate analysis showed that mortality was higher (p < 0.0001) and use of thrombolysis, beta blockers, and acetylsalicylic acid was lower (p < 0.0001) in patients 70 years of age and older, compared with younger patients, and in women, compared with men. Multivariate analysis of the entire patient sample revealed age of 75 years or older (154 percent) and age 70 to 74 years (141 percent) to be associated with the highest relative risk of death in hospital. The increased relative risk associated with previous AMI was 45 percent. Acetylsalicylic acid use was associated with the greatest decrease in relative risk of death (-69 percent), followed by beta blockers (-36 percent) and thrombolysis (-31 percent). These patterns of relative risk were the same for men and women. CONCLUSIONS: Among contemporary AMI patients, advanced age and female sex are associated with relative under-utilization of proven effective medical therapy and increased risk of dying in the hospital. Although the contribution of age to AMI risk appears greater than that of gender, survival in any high risk group would likely be improved by increased use of proven medical therapy.

QRST changes during and after percutaneous transluminal coronary angioplasty.

This study reports preliminary results on 45 patients who underwent percutaneous transluminal coronary angioplasty (PTCA); 120-lead data (including the 12-lead standard electrocardiogram [ECG]) were recorded before, during, and after balloon inflation. Twenty-one patients underwent PTCA for left anterior descending coronary disease, 13 for right coronary artery disease, and 10 for left circumflex; 1 patient had combined left anterior descending and right coronary artery disease. In each patient, voltage data recorded during the various phases of the procedure were compared with the patient's own baseline data. In 18 patients, 120 leads were also recorded 24 hours after PTCA. In this study, the usefulness of the standard 12-lead ECG was investigated in locating the coronary artery being occluded, in elucidating the mechanisms of the QRS changes, and in identifying changes occurring 24 hours after completion of the procedure. Results indicate that the observation of ST elevation in the 12-lead ECG may lead to ambiguous interpretation. Also, limiting observation to ST-T patterns alone instead of including QRS changes further hampers correct identification of the involved vessel. QRS modifications during inflation are interpreted as conduction disturbances, although other mechanisms are evoked: study of surface maps may contribute to the understanding of these mechanisms. Changes present 24 hours later are visible in the standard leads, but again, in the absence of the thoracic potential distribution, these are difficult to interpret. These changes were different from those observed after cessation of inflation at the end of the procedure. It is hypothesized that next-day changes may reflect reperfusion injury and/or represent myocardial stunning. Presence of injury and reversibility of changes require further investigation. Also, biochemical markers such as creatine kinase-MB mass, creatine kinase-MB activity, myoglobin, and troponin-T may help elucidate the significance of these findings.

Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose.

Plasma concentrations and urinary excretion of DTZ and its metabolites were determined in 20 healthy volunteers (10 males and 10 females) after they had each been given a single oral 90 mg dose of DTZ. DTZ and six of its metabolites which included N-monodesmethyl DTZ (MA), deacetyl DTZ (M1), deacetyl N-monodesmethyl DTZ (M2), deacetyl O-desmethyl DTZ (M4) and deacetyl DTZ N-oxide (M1NO) and deacetyl N,O-didesmethyl DTZ (M6), were determined by a sensitive and specific HPLC assay. The major metabolites measurable in the plasma of all the volunteers were MA, M1, and M2. The terminal half-lives (t1/2) of M1 and M2 were considerably longer than those of DTZ and MA. Less than 5% of the dose was excreted as unchanged DTZ in the urine over the 24 h period. The major urinary metabolite was MA, followed by M6, M2, and then M1. Except for the urinary excretion of M4 there were no statistically significant differences in any of the pharmacokinetic parameters between the males and the females. The mean 24 h urinary recovery of M4 was higher in the males than in the females (P < 0.05). However there were large inter-individual variations in the plasma concentrations and urinary excretion of DTZ and its metabolites with some parameters differing by more than 20-fold. In addition, O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) were identified as two other major urinary metabolites.

Body surface potential mapping of ST segment changes in acute myocardial infarction. Implications for ECG enrollment criteria for thrombolytic therapy.

BACKGROUND: Several large, randomized clinical trials have shown that early thrombolytic therapy substantially reduces early mortality after acute myocardial infarction (MI). In most trials, eligibility criteria include typical chest pain and diagnostic ST segment elevation in two or more contiguous leads of the standard 12-lead ECG. Unfortunately, large areas of the thoracic surface are left unexplored by the standard electrode positions. As a consequence, acute MI patients with ST elevation in regions not interrogated by the conventional electrodes may not receive reperfusion therapy and its attendant benefits. METHODS AND RESULTS: The present study compares 120-lead body surface potential map (BSPM) data from 131 patients with acute MI and 159 normal control subjects (N). The MI population was stratified according to the location of ventricular wall motion abnormalities evidenced by radionuclide imaging into 76 patients with anterior MI (AMI), 32 patients with inferior MI (IMI), and 23 patients with posterior MI (PMI). BSPM were recorded within 24 hours of admission. Group mean BSPM of the ST segment were obtained for N, AMI, IMI, and PMI by sampling the time-normalized ST-T waveform at 18 equal intervals and averaging the voltages at each electrode site over the first five of these 18 ST-T time instants. Corresponding discriminant maps were also computed for each pairwise comparison (AMI versus N, IMI versus N, and PMI versus N) by subtracting the normal group mean voltages from each MI group mean voltages and by further dividing each resulting difference by the composite standard deviation calculated from the pooled groups. Discriminant analysis for each bigroup classification was also performed using as measurements the ST magnitudes in 120 electrode sites from each individual. Finally, the number of patients in each MI group with ST changes outside the 95% normal range was calculated for each electrode position. The following results were obtained: 1) In each MI group, ST depression departs more significantly from normal values than ST elevation. 2) The most significant ST changes (both ST elevation and ST depression) are observed in IMI, the least significant in AMI. 3) For each pairwise comparison, measurements from two lead sites are entered into the stepwise discriminant procedure: the first measurement is ST depression, the second ST elevation. Classification rates are 82% for AMI, 93% for PMI, and 100% for IMI at a specificity level of 95%. 4) From the six leads selected for optimal classification of the three MI groups, five are outside the area sampled by the conventional precordial electrodes. 5) The use of site-dependent thresholds for ST measurements based on 95% normal range yields the best compromise between sensitivity and specificity. A fixed threshold of 1 mm for ST elevation or ST depression produces increased sensitivity in AMI at the cost of marked loss in specificity and reduces sensitivity in both IMI and PMI with no benefit in specificity. CONCLUSIONS: Analysis of BSPM identifies areas on the torso where the most significant ST changes most frequently occur in acute MI. Two leads from areas with the most abnormal ST changes achieve optimal classification in each MI class. Of these six leads, five are outside the standard precordial lead positions. ST depression is the most potent discriminator for each MI group and contains information independent from ST elevation. Quantitative analysis of ST magnitude at each electrode site allows determination of best thresholds for ECG criteria. Appropriate selection of ECG leads may help remove inconsistencies in current ECG selection criteria and improve comparability of treatment results.

Changes in acute myocardial infarction risk and patterns of practice for patients older and younger than 70 years, 1987-90.

OBJECTIVE: To evaluate temporal changes in risk and patterns of hospital practice for acute myocardial infarction (AMI). DESIGN/PATIENTS: Retrospective analysis of age-related medical therapy and outcome of 342 consecutive patients (132 at least 70 years old and 210 younger than 70) with AMI between July 1, 1989, and June 30, 1990, and comparison with data from two previous analyses of AMI practice in 1987 (n = 207) and 1988-89 (n = 402). SETTING: Tertiary care medical centre. INTERVENTIONS: No direct interventions; results of the two previous AMI practice pattern analyses, however, were propagated during the practice time of the most recent analysis. RESULTS: In 1989-90, hospital mortality was higher (19%) among patients at least 70 years old compared with patients younger than 70 (8%) (P less than 0.01). Therapies proven by repeated clinical trials to be effective in reducing AMI risk were all used less frequently in patients aged at least 70 years: thrombolysis (20 versus 43%); beta-blockers (41 versus 62%); acetylsalicylic acid (71 versus 87%); and nitrates (86 versus 97%). Qualitatively, these age-specific patterns of AMI mortality and therapy were similar to previous studies. Quantitatively, however, comparing 1987 with 1989-90 demonstrated parallel and marked increases in the use of all proven medications in both age groups, ranging from 42 to 230% (P less than 0.01). There was also a significant overall decrease in mortality from the 1987 patient cohort (20%) to the 1989-90 cohort (13%) (P less than 0.05). The decrease in mortality was entirely due to decreased mortality within the group 70 years or older; 35% in 1987 versus 19% in 1989-90 (P less than 0.05). Mortality in the AMI patients younger than 70 years old remained unchanged from 1987 to 1989-90. CONCLUSIONS: Pattern of practice analyses were associated with, and may have contributed to, improved patient care and outcomes in AMI. Increased use of effective AMI medical therapy had a greater benefit in elderly higher risk AMI patients than lower risk younger patients. Persisting age-specific differences in AMI therapy may respond to more direct quality improvement measures, such as critical path management.

Contemporary medical management of left ventricular dysfunction and congestive heart failure.

OBJECTIVE: The primary purpose of this review was to address the following question: based on the best available evidence, what should be the current medical management of congestive heart failure (CHF)? DATA SOURCES: The major sources for this review were from searches of the English language literature, including computer and bibliography reviews, of all randomized, controlled clinical trials and overview analyses of positive inotropic agents, preload/afterload reduction agents and beta-blocker medications in CHF. STUDY SELECTION: The number of studies reviewed was approximately 40. The major criterion for selection was that the studies be of CHF patients in randomized controlled clinical trials, particularly with a mortality/survival endpoint. Additional clinical trials of nonmortality endpoints in CHF patients and mortality trials in non-CHF patients were also selected to support possible pathophysiological insights for future CHF trials. DATA EXTRACTION: The data, particularly for the accompanying tables, were initially extracted by a single reviewer using common qualitative guidelines as far as was possible within the different temporal, etiological and geographic frameworks of the original component studies. Conclusions are drawn from this data synthesis and from published overviews. DATA SYNTHESIS: Angiotensin converting enzyme (ACE) inhibition therapy is effective in reducing mortality and morbidity in severe left ventricular dysfunction and CHF. Other systemic vasodilators may also be beneficial. The effects of digitalis on survival and morbidity in CHF are presently uncertain, but should be resolved in the near future. Other inotropic agents, at least in the long term, are clinically detrimental. Diuretics decrease morbidity, but their effect on mortality in CHF remains unknown. Beta-blocker and magnesium therapy offer promise in CHF, but await definitive clinical trials evaluation. CONCLUSIONS: The current medical therapy of CHF should definitely include ACE inhibitors, probably diuretics and possibly other vasodilators. Further viable trials of promising new, and older heretofore under-evaluated, CHF therapies are needed. Additionally, innovative strategies are needed to deal with this disease which has an increasing prevalence. Two strategies, primary prevention of CHF and a 'Heart Function Clinic', are discussed.