Mathematically aggregating experts' predictions of possible futures.

Structured protocols offer a transparent and systematic way to elicit and combine/aggregate, probabilistic predictions from multiple experts. These judgements can be aggregated behaviourally or mathematically to derive a final group prediction. Mathematical rules (e.g., weighted linear combinations of judgments) provide an objective approach to aggregation. The quality of this aggregation can be defined in terms of accuracy, calibration and informativeness. These measures can be used to compare different aggregation approaches and help decide on which aggregation produces the "best" final prediction. When experts' performance can be scored on similar questions ahead of time, these scores can be translated into performance-based weights, and a performance-based weighted aggregation can then be used. When this is not possible though, several other aggregation methods, informed by measurable proxies for good performance, can be formulated and compared. Here, we develop a suite of aggregation methods, informed by previous experience and the available literature. We differentially weight our experts' estimates by measures of reasoning, engagement, openness to changing their mind, informativeness, prior knowledge, and extremity, asymmetry or granularity of estimates. Next, we investigate the relative performance of these aggregation methods using three datasets. The main goal of this research is to explore how measures of knowledge and behaviour of individuals can be leveraged to produce a better performing combined group judgment. Although the accuracy, calibration, and informativeness of the majority of methods are very similar, a couple of the aggregation methods consistently distinguish themselves as among the best or worst. Moreover, the majority of methods outperform the usual benchmarks provided by the simple average or the median of estimates.

Dipyridamole-thallium/sestamibi before vascular surgery: a prospective blinded study in moderate-risk patients.

PURPOSE: This study assessed in a prospective, blinded fashion whether a reversible defect on dipyridamole-thallium (DTHAL)/sestamibi (DMIBI) can predict adverse cardiac events after elective vascular surgery in patients with one or more clinical risk factors. METHODS: Consecutive patients with one or more clinical risk factors underwent a preoperative blinded DTHAL/DMIBI. Patients with recent congestive heart failure (CHF) or myocardial infarction (MI) or severe or unstable angina were excluded. RESULTS: Eighty patients (78% men; mean age, 65 years) completed the study. Diabetes mellitus was the most frequent clinical risk factor (73%), followed by age older than 70 years (41%), angina (29%), Q wave on electrocardiogram (26%), history of CHF (7%), and ventricular ectopy (3%). The results of DTHAL/DMIBI were normal in 36 patients (45%); a reversible plus or minus fixed defect was demonstrated in 28 patients (36%), and a fixed defect alone was demonstrated in 15 patients (19%). Nine adverse cardiac events (11%) occurred, including three cases of CHF, and one case each of unstable angina, Q wave MI, non-Q wave MI, and cardiac arrest (successfully resuscitated). Two cardiac deaths occurred (2% overall mortality), one after a Q wave MI and one after CHF and a non-Q wave MI. The cardiac event rate was 14% for reversible defect and 9.8% without reversible defect (P =.71). The cardiac event rate was 12.5% (one of eight cases) for two or more reversible defects, versus 11.1% (eight of 72 cases) for fewer than two reversible defects (P = 1.0). The sensitivity rate of two or more areas of redistribution was 11% (95% CI, 0.3%-48%), the specificity rate was 90%, and the positive and negative predictive values were 12.5% and 89%, respectively. CONCLUSION: Our study demonstrated no association between reversible defects on DTHAL/DMIBI and adverse cardiac events in moderate-risk patients undergoing elective vascular surgery.

Antiarrhythmic agents for atrial fibrillation: focus on prolonging atrial repolarization.

Atrial fibrillation (AF) has been the subject of considerable attention and intensive clinical research in recent years. Current opinion among physicians on the management of AF favors the restoration and maintenance of normal sinus rhythm. This has several potential benefits, including the alleviation of arrhythmia-associated symptoms, hemodynamic improvements, and possibly a reduced risk of thromboembolic events. After normal sinus rhythm has been restored, antiarrhythmic therapy is necessary to reduce the frequency of AF recurrence. In the selection of an antiarrhythmic agent, both efficacy and safety should be taken into consideration. Many antiarrhythmic agents have the capacity to provoke proarrhythmia, which may result in an increase in mortality. This is of particular concern with sodium-channel blockers in the context of patients with structural heart disease. Flecainide and propafenone are well tolerated and effective in maintaining sinus rhythm in patients without significant cardiac disease but with AF. Recent interest has focused on the use of class III antiarrhythmic agents, such as amiodarone, sotalol, dofetilide (recently approved), ibutilide (approved for chemical conversion of AF and atrial flutter), and azimilide (still to be approved) in patients with AF and structural heart disease. To date, amiodarone and sotalol still hold the greatest interest, and although controlled clinical trials with these agents have been few, a number are in progress and some have been recently completed. These agents are effective in maintaining normal sinus rhythm in patients with paroxysmal and persistent AF and are associated with a low incidence of proarrhythmia when used appropriately. Because of the relative paucity of placebo-controlled trials of antiarrhythmic agents in patients with AF, experience until recently has tended to dictate treatment decisions. Increasingly, selection of drug therapy is being based on a careful and individualized benefit-risk evaluation by means of controlled clinical trials, an approach that is likely to dominate the overall approach to the control of atrial fibrillation in the largest numbers of cases of the arrhythmia. Pharmacologic therapy is likely to be dominated by compounds that exert their predominant effect by prolonging atrial repolarization.

Trimetazidine-induced enhancement of myocardial glucose utilization in normal and ischemic myocardial tissue: an evaluation by positron emission tomography.

Trimetazidine has an anti-ischemic effect in angina pectoris. This agent has no hemodynamic effects, and its benefit is presumed to be based on a metabolic mechanism of action. A group of 33 dogs undergoing openchest left anterior descending coronary artery (LAD) ligation causing prolonged ischemia were imaged with quantitative positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) to measure regional glucose metabolic utilization (rGMU) and [11C]acetate to measure regional monoexponential washout rate constant (Kmono) for oxidative metabolism in nonrisk and ischemic-risk myocardium. A total of 20 dogs were pretreated with trimetazidine at low dose (n = 10, 1 mg/kg) and high dose (n = 10, 5 mg/kg) and compared with 13 control dogs. Microsphere-measured myocardial blood flow (mL/min/g) was measured preocclusion and repeated hourly after occlusion and expressed as a ratio of preocclusion myocardial blood flow to verify a stable level of ischemia during PET. No differences were seen in postocclusion ischemic risk/nonrisk myocardial blood flow between treatment groups (p = not significant [NS]). Preocclusion and hourly measurements of heart rate and blood pressure corrected for baseline revealed no difference in control dogs versus trimetazidine (low-dose and high-dose) groups (p = NS). 18FDG-derived rGMU (micromol/min/g) was increased in high-dose trimetazidine versus control dogs in nonrisk and ischemic risk groups, respectively (1.16+/-0.57 vs 0.51+/-0.38 and 0.43+/-0.29 vs 0.20+/-0.14; p <0.05). rGMU was increased proportionately in nonrisk and ischemic risk in all groups without significant differences when corrected for nonrisk rGMU (ischemic risk/nonrisk was 0.92+/-1.3 vs 0.64+/-0.66 vs 0.40+/-0.22 for control dogs, all trimetazidine and high-dose trimetazidine groups). Kmono (min(-1) was not altered in any group (nonrisk = 0.13+/-0.03 vs 0.13+/-0.03 vs 0.14+/-0.02 and ischemic risk = 0.18+/-0.05 vs 0.17+/-0.06 vs 0.16+/-0.06 for control dogs, all trimetazidine and high-dose trimetazidine groups, respectively; p = NS for nonrisk vs ischemic risk, between and within groups). Our data verify that trimetazidine does not alter hemodynamic porameters. It increases total glucose utilization (oxidative and glycolytic) in myocardium without preferential increase in ischemic tissue. Absence of change in total oxidative metabolism suggests increased glucose metabolism is predominantly glycolysis or an increase in glucose oxidation with similar decrease in fatty acid oxidation.

Efficacy of a nicotine inhaler in smoking cessation: a double-blind, placebo-controlled trial.

A non-combustible nicotine inhaler, administered orally, has been developed for treatment of smokers. The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking. Subjects were randomly assigned to active (n = 112) and placebo (n = 111) groups. Some behavioral intervention occurred as a function of participation. Strict abstinence (primary outcome criterion) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year. Survival analysis showed active inhaler was superior to placebo (p < 0.01). Active vs. placebo success rates were: 63% vs. 47% (day 3), 46% vs. 28% (week 1), 36% vs. 19% (week 2), 33% vs. 16% (week 3), 29% vs. 14% (week 6), 24% vs. 10% (3 months), 17% vs. 9% (6 months) and 13% vs. 8% (1 year). chi 2 analyses were significant through 3 months but not at 6 months (p < 0.08) or 1 year. Craving was relieved with active inhalers at day 3 and week 1. Subjects averaged six inhalers/day. Cotinine levels were 57-61% of smoking levels. Common side effects included throat/mouth irritation and coughing. Failure was predicted by early slips. The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy. Extended access to the inhaler and relapse prevention training could improve success rates. Another promising approach would be to combine the inhaler with a nicotine patch.

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial.

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safety and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8-32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO < or = 8 ppm; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.

Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction.

Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction have a high but variable annual mortality and some may benefit from myocardial revascularization. This study aimed to evaluate the prognostic value of positron emission tomography (PET), and its interrelation with the choice of medical therapy or revascularization for predicting survival and improvement in symptoms of heart failure in patients with CAD and LV dysfunction. Ninety-three consecutive patients with angiographic CAD and a mean LV ejection fraction of 0.25 who underwent cardiac PET studies for assessment of hypoperfused yet viable myocardium ("mismatch pattern") using N-13 ammonia and 18-F deoxyglucose were followed up for an average of 13.6 months. Fifty patients underwent medical treatment and 43 underwent revascularization. The Cox model analysis showed that the extent of mismatch had a negative effect (p = 0.02), whereas revascularization had a positive effect on survival (p = 0.04). The annual survival probability of patients with mismatch receiving medical therapy was lower than of those without mismatch (50 vs 92%, p = 0.007). Patients with mismatch who underwent revascularization had a higher survival rate than those treated medically (88 vs 50%, P = 0.03). The presence of mismatch also predicted improvement in heart failure symptoms after revascularization (p < 0.001). These results suggest that the presence of mismatch in patients with CAD and severe LV dysfunction is associated with poor annual survival with medical therapy. Revascularization in patients with PET mismatch appears to be associated with improved survival and heart failure symptoms.

Persistent twenty-four hour SPECT thallium-201 defects, plasma thallium-201 concentrations and PET metabolic viability.

Previous studies have shown that defects on four hour thallium-201 redistribution images often exhibit late reversibility, suggesting that the thallium-201 scintigraphic assessment of myocardial viability might be influenced by delayed redistribution imaging. To assess tissue metabolic activity in segments with late thallium-201 defects, positron emission tomography (PET) with 13NH3 and 18FDG was performed in 26 coronary artery disease patients with left ventricular dysfunction undergoing twenty-four hour SPECT thallium-201 scintigraphy. In 13 patients, plasma thallium-201 levels were obtained at the time of SPECT study and integrated tracer concentrations were determined one, two, four and twenty-four hours following injection. On circumferential profile image analysis of the PET images, ischemia was defined by preserved glucose metabolism in hypoperfused myocardium while infarction was identified by concordant reductions in both perfusion and glucose metabolism. Nineteen patients had stress-redistribution SPECT studies and seven had rest-redistribution SPECT studies. Using a semi-quantitative scoring system, four experienced observers visually identified 100 fixed, 17 partially reversible and twelve completely reversible segmental SPECT thallium-201 defects. On PET, metabolic activity was identified in 51 (51%) fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) partially reversible defects (five PET ischemia, four PET normal). Of the twelve completely reversible thallium-201 defects, six (50%) were normal on PET, five (42%) had PET ischemia and one (8%) had PET infarction. The relative number of fixed thallium-201 defects with metabolic activity on PET did not depend on whether a stress or rest thallium-201 study was performed, or on whether the plasma thallium-201 integral concentration was high or low relative to mean values at any time point. Despite delayed redistribution imaging, PET imaging identifies glucose metabolic activity, and therefore residual tissue viability, in the majority of fixed twenty-four hour thallium-201 defects.

Metabolism in non-ischemic myocardium during coronary artery occlusion and reperfusion.

Blood flow and metabolism in non-ischemic myocardium were studied at baseline and during occlusion and reperfusion of the left anterior descending coronary artery in closed chest dogs using positron emission tomography. Myocardial blood flow (MBF) and oxygen consumption (MVO2) in non-ischemic tissue were each increased by 28% relative to the rate pressure product during occlusion, consistent with increased work to compensate for the dyskinetic segment. MVO2 in non-ischemic sectors remained elevated relative to the rate pressure product early (1-2 h) post-reperfusion, 21% above baseline, but subsequently normalized. When sectors with normal blood flow during occlusion were divided into sectors adjacent to and remote from the risk zone, MBF in the 2 sector groups was similar at all times, but metabolic differences were found. MVO2 was depressed by 15% in adjacent relative to remote sectors 1 day post-reperfusion, with a concomitant 62% increase in glucose metabolic rate; relative increases in glucose metabolism were found only when glucose metabolism was low in remote myocardium, suggesting a decreased suppressibility of glucose metabolism in adjacent myocardium. The kinetics of (1-11C] palmitate were also altered in adjacent sectors, consistent with a small increase in esterification relative to oxidation of long chain fatty acids. Thus, sectors adjacent to ischemic segments show metabolic changes similar to those seen in reversibly injured post-ischemic tissue, despite normal blood flow during occlusion.

Regional myocardial blood flow and glucose utilization in symptomatic patients with hypertrophic cardiomyopathy.

BACKGROUND: Previous studies suggested the presence of myocardial ischemia in symptomatic patients with hypertrophic cardiomyopathy. Positron emission tomography, a technique that can identify metabolic consequences of ischemia in coronary artery disease, permits the noninvasive measurements of regional myocardial blood flow and glucose metabolism. This new quantitative imaging approach should therefore be suitable for detecting a possible enhancement of glucose utilization in myocardium of patients with hypertrophic cardiomyopathy and thus may help to elucidate the pathomechanism of ischemia in this disease. METHODS AND RESULTS: In 13 symptomatic patients with hypertrophic cardiomyopathy, myocardial blood flow and glucose utilization were measured with intravenous N-13-ammonia and F-18 deoxyglucose at rest and, in four patients, again during supine bicycle exercise. At rest, blood flow was significantly lower in hypertrophied than in normal myocardium (0.78 +/- 0.19 versus 0.99 +/- 0.13 mL.min-1.g-1, p < 0.025), whereas rates of glucose utilization were similar (0.88 +/- 0.31 versus 0.87 +/- 0.35 mumol.min-1.g-1). With exercise, blood flow and glucose utilization failed to increase in hypertrophic and normal segments but became more heterogeneously distributed throughout the left ventricular myocardium. Blood flow-metabolism mismatches indicative of myocardial ischemia were noted in three patients at rest and in three of the four patients during exercise and were due to reduced flow in the presence of maintained glucose uptake. The discordance between flow and glucose metabolism in hypertrophied myocardium was significantly more prominent in younger than in older patients. CONCLUSIONS: Normal or even elevated rates of glucose utilization and the presence of diminished blood flow in hypertrophied relative to normal myocardium suggest the presence of myocardial ischemia in symptomatic hypertrophic cardiomyopathy. The age dependence of blood flow metabolism disparity suggests differences in the underlying pathophysiology or severity of disease.

Blood flow-dependent uptake of indium-111 monoclonal antimyosin antibody in canine acute myocardial infarction.

OBJECTIVES: The relation of myocardial blood flow and indium-111 (111In) antimyosin antibody uptake was studied by inducing myocardial infarction in 18 dogs, 8 with closed chest left anterior descending artery balloon occlusion for 3 h followed by reperfusion (group A) and 10 dogs with open chest left anterior descending artery ligation (without reperfusion, group B). BACKGROUND: The relation of antimyosin uptake to myocardial injury has been documented. However, its relation to tracer delivery by myocardial blood flow has not been studied and has been assumed to be independent. METHODS: Indium-111 antimyosin antibody, 2 mCi, was injected 20 min after reperfusion and 3 h after coronary artery ligation in groups A and B, respectively. Regional blood flows were determined by radiolabeled microspheres during occlusion and 24 h later in both groups. On day 2, dogs were killed after risk zone delineation with gentian violet. The heart was excised and stained with triphenyltetrazolium chloride solution and graded for increasing severity of tissue injury based on extent of staining. Microsphere activity and 111In antimyosin activity were measured in control tissue (grade 1), noninfarct tissue at risk (grade 2), mixed tissue (grade 3), infarct tissue (grade 4) and hemorrhagic infarct tissue (grade 5, present only in group A dogs). Count activity was normalized to that of the mean value in control tissue (grade 1) and expressed as a ratio of activity. RESULTS: Indium-111 antimyosin activity was high in triphenyltetrazolium chloride grade 4 tissue in both groups but was attenuated in grade 4 tissue in group B dogs (10.6 +/- 5.1 vs. 5.0 +/- 4.5; p < 0.05 group A vs. group B), which had lower blood flow on day 2 (0.51 +/- 0.36 vs. 0.23 vs. 0.22; p < 0.01). Normalizing 111In antimyosin activity for blood flow on day 2 resulted in equivalent 111In antimyosin uptake for infarct tissue (32.6 +/- 21.6 vs. 36.6 +/- 29.8 for group A vs. group B; p = NS). CONCLUSIONS: Thus, 111In antimyosin uptake is a specific marker of necrotic tissue with a high signal ratio in reperfused tissue. However, its uptake is dependent on residual blood flow in the infarct territory. Indium-111 antimyosin could potentially serve as a suitable tracer for infarct sizing if myocardial blood flow in the same region were factored simultaneously.

Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.

BACKGROUND: Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS: On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS: In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

BACKGROUND: Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography. METHODS AND RESULTS: Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was decreased less than myocardial blood flow, consistent with increased oxygen extraction in the ischemic tissue. After reperfusion, blood flow normalized rapidly in reversibly injured tissue but remained depressed in infarct-containing sectors. Regional myocardial function, assessed by two-dimensional echocardiography, was severely depressed during occlusion and did not improve significantly until 1 week after reperfusion. MVO2 remained depressed after reperfusion in both reversibly injured and infarct-containing sectors, did not improve from occlusion levels until 1 week after reperfusion, and remained significantly depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate kinetics were also abnormal in postischemic tissue. As reported previously, glucose metabolic rates were increased relative to baseline in normal but not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose metabolism tended to be higher in postischemic relative to normal myocardium. CONCLUSIONS: The results demonstrate decreased oxidative metabolism in postischemic tissue, with concomitant abnormalities in palmitate kinetics and glucose metabolism. Oxidative metabolism and regional function demonstrated a parallel recovery with time.

Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography.

To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients). Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%. Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease. The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%. An index incorporating both number and severity of defects derived from circumferential profile analysis was significantly lower in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/- 0.8 versus 2.7 +/- 2.4; p less than 0.005). Thus, noninvasive positron emission tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy, and a semiquantitative index such as circumferential profile analysis is superior to that of visual analysis alone.

Myocardial ischemia during cocaine withdrawal.

STUDY OBJECTIVE: To determine the prevalence of myocardial ischemia in patients with cocaine addiction. DESIGN: Myocardial ischemia in chronic cocaine users was detected by serial 24-hour electrocardiographic ambulatory (Holter) monitoring and exercise treadmill testing in chronic cocaine users. The Holter tapes were coded, scanned in a blinded manner, and mixed with the tapes of 42 normal volunteers and 119 patients with either stable or unstable angina. SETTING: A 28-day inpatient, substance abuse treatment program followed by an outpatient treatment program. PATIENTS: Twenty-one consecutive male chronic cocaine users. MAIN RESULTS: Eight of the 21 patients with cocaine addiction had frequent episodes of ST elevation during Holter monitoring; these episodes occurred almost exclusively during the first 2 weeks of withdrawal. None of the volunteers and patients with stable angina and only 4% of the patients with unstable angina had episodes of ST elevation during Holter monitoring (cocaine users compared with volunteers, P = 0.0004). Of the 20 cocaine patients who had exercise treadmill testing, only 1 had a positive test for ischemia. CONCLUSIONS: Cocaine users frequently develop silent myocardial ischemia manifesting as episodes of ST elevation during the first weeks of withdrawal. The underlying mechanisms for these changes remain unknown, but our observations support the hypothesis that coronary vasospasm plays an important role in cocaine-related ischemic syndromes.

Variability of indexes for myocardial ischemia: a comparison of exercise treadmill test, ambulatory electrocardiographic monitoring and symptoms of myocardial ischemia.

Fifty-four patients with chronic stable angina were studied to determine and compare weekly variability of indexes for the detection of myocardial ischemia. All patients underwent three single-blind placebo periods, each lasting 1 week. An exercise treadmill test, 24 h ambulatory electrocardiographic (Holter) monitoring (analyzed blindly) and an accurate diary of anginal attacks and nitroglycerin use were obtained at the end of each placebo period. An unbalanced, completely random component of variance analysis was used to calculate a component for within subject variability and a component for among subject variability. The coefficient of variation and percent variation (within subjects) of onset of chest pain during exercise were 19% and 30%, respectively; the corresponding values were 28% and 33% for onset of 1 mm ST depression, 15% and 15% for exercise duration, 44% and 27% for number of ischemic episodes/24 h, 56% and 43% for anginal frequency and 55% and 27% for nitroglycerin consumption, respectively. With use of this statistical method and variation within subjects, the change in the value of each variable necessary to exceed those attributable to spontaneous variation was determined. The trade-off between repeated measurements and number of subjects, the sample size estimated for planning studies and the minimal sample size for using various designs were also determined. Although the data indicate that all indexes for myocardial ischemia, both during exercise and during daily activity, vary considerably, but the exercise variables have less variability and are more reproducible.(ABSTRACT TRUNCATED AT 250 WORDS)

Severity of silent myocardial ischemia on ambulatory electrocardiographic monitoring in patients with stable angina pectoris: relation to prognostic determinants during exercise stress testing and coronary angiography.

The relation of silent ischemia in patients with stable angina to known predictors of severity of coronary disease on exercise stress testing and coronary angiography is poorly defined. This issue was therefore examined with use of Holter electrocardiographic (ECG) recordings, treadmill exercise tests and angiographic indexes in 102 patients (not taking antianginal therapy) and the results were compared with Holter and treadmill findings in 42 volunteers. A total of 159 ischemic episodes (90% silent) were identified during 2,503 h on Holter recording in 97 patients (mean duration per episode 22.7 +/- 147 min; range 1 to 234). Holter recordings had a 92% specificity and an 80% positive predictive value, but a sensitivity of only 37% and a negative predictive value of 27% for coronary disease. Sixty-three patients (Group I) had no ischemia on Holter recording, 22 (Group II) had a cumulative duration of 1 to 60 min/24 h and in 12 (Group III) ischemia exceeded 60 min/24 h. There was no significant correlation between cumulative ischemia duration on Holter recording and exercise duration or time to ST segment depression on treadmill exercise. In general, the greater the number of coronary vessels involved and the higher the proximal coronary artery stenosis score, the greater the likelihood of ischemia and the longer the cumulative ischemia duration on Holter recording. Irrespective of the severity of coronary disease, in about 25% of Holter recordings in each angiographic category there were no ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of silent myocardial ischemia in patients with unstable angina.

Silent myocardial ischemia is common in unstable angina, but its prognostic significance is unknown. Fifty-two (42 with subsequent angiography) of 81 patients prospectively evaluated for unstable angina had ambulatory electrocardiographic (Holter) recordings analyzed by compact analog technique after they had received medical treatment (3 of the 52 had unanalyzable recordings and were excluded). From 1,103 hours of recordings, 298 ischemic episodes were identified, only 9% associated with angina. By Ridit analysis a significant correlation was found between the cumulative duration of transient myocardial ischemia and the number of diseased coronary vessels and indexes of proximal stenosis. During a 3 to 6 month follow-up period, there was one death and one patient was lost to follow-up among 20 patients without transient ischemia; in the group of 11 patients with a cumulative duration of transient ischemia less than 60 minutes/24 h, 7 were alive and well, 2 required coronary bypass surgery, 1 had coronary angioplasty for recurrence of angina and 1 was lost to follow-up. In the group of 18 patients with ischemia duration greater than 60 minutes/24 h, only 1 developed a stable angina pattern; 12 required coronary surgery (n = 11) or angioplasty (n = 1) and 5 developed myocardial infarction (2 died, 2 needed surgery for postinfarction angina and 1 recovered). A favorable clinical outcome occurred in only 6% of patients in the group with ischemia duration greater than 60 minutes/24 h; this rate was significantly lower (p less than 0.001) than that (70%) for the group with ischemia duration less than 60 minutes/24 h or that (95%) for the group without ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)