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Objectives: This study examined gender differences and temporal changes in the clinical characteristics of patients referred for nuclear stress imaging, their imaging results and subsequent utilization of coronary angiography and revascularization., Background: Gender bias may influence resource utilization in patients with coronary artery disease (CAD). No study has analyzed gender differences and time trends in patients referred for noninvasive testing and subsequent use of invasive procedures., Methods: Between January 1986 and December 1995, 14,499 patients (5,910 women and 8,589 men) without established CAD underwent stress myocardial perfusion imaging. The clinical characteristics, imaging results, coronary angiograms and revascularization outcomes were compared in women and men over time., Results: The mean pretest probability of CAD was lower in women (45%) than in men (70%) (p < 0.001). More women (69%) than men (42%) had normal nuclear images (p < 0.001). Men (17%) were more likely than women (8%) to undergo coronary angiography (p < 0.001). Male gender was independently associated with referral for coronary angiography (multivariate model: chi-square = 16, p < 0.001) but was considerably weaker than the imaging variables (summed reversibility score: chi-square = 273, p < 0.001). Revascularization was performed in more men (46% of the population undergoing angiography) than women (39%) (p = 0.01), but gender was not independently associated with referral to revascularization. There were no significant differences in clinical, imaging or invasive variables between the genders over time., Conclusions: There was little evidence for a bias against women in this study. Women were somewhat less likely to undergo coronary angiography but were referred for stress perfusion imaging more liberally. Practice patterns remained constant over this 10-year period.

Objective: The objective was to investigate mechanisms of vasovagal syncope by identifying laboratory techniques that characterize cardiovascular profiles in patients with vasovagal syncope., Background: The triggering mechanisms of vasovagal syncope are complex. The patient population is likely heterogeneous. We hypothesized that distinct hemodynamic profiles are definable with provocative maneuvers., Methods: Three groups of subjects were matched for age and gender: 16 patients with a history of syncope and an inducible vasovagal response during passive tilt table testing (70 degrees, 45 min, group I), 16 with a history of syncope, negative passive tilt table testing but positive isoproterenol tilt table testing (0.05 microg/kg per min, 70 degrees, 10 min, group II), and 16 control subjects. Beat-to-beat hemodynamic functions were determined noninvasively by photo-plethysmography and impedance cardiography., Results: At baseline, hemodynamic functions were not different among the three groups (supine). In response to tilt before any symptoms developed, total peripheral resistance decreased 9% +/- 14% in group I from baseline supine to tilt position but increased 27% +/- 18% in group II and 28% +/- 17% in controls (p < 0.001). Responses to isoproterenol were not significantly different between group II and controls in supine position. In response to tilt during isoproterenol infusion before any symptoms developed, total peripheral resistance decreased 24% +/- 20% in group II and increased 20% +/- 48% in controls (p = 0.002)., Conclusions: Group I patients may have impaired ability to increase vascular resistance during orthostatic stress. The inability to overcome isoproterenol-induced vasodilatation during tilt is important in triggering a vasovagal response in group II patients. These data suggest that the population with vasovagal response is heterogeneous. Distinct hemodynamic profiles in response to various provocative maneuvers are definable with noninvasive, continuous monitoring techniques.

Objectives: The aim of this study was to determine which clinical, exercise and thallium variables can aid in the identification of three-vessel or left main coronary artery disease (3VLMD) in patients with one abnormal coronary territory (either a reversible or fixed defect) on exercise thallium testing and to test the prognostic value of these variables., Background: Although the sensitivity of detection of coronary artery disease by thallium-201 imaging is high, the actual detection of 3VLMD by thallium tomographic images alone is not optimal., Methods: A multivariate model for prediction of 3VLMD was developed from several clinical, exercise and thallium-201 variables in a training population of 264 patients who had one abnormal coronary artery territory on exercise thallium testing and had undergone coronary angiography. Using this model, patients were stratified into risk groups for prediction of 3VLMD. A separate validation cohort of 474 consecutive patients who were treated initially with medical therapy and who had one abnormal coronary territory were divided into identical risk groupings by the variables derived from the training population, and they were followed for a median of 7.0 years to evaluate the prognostic value of this model., Results: The prevalence of 3VLMD was 26% in the training population despite one abnormal thallium coronary territory. Four clinical and exercise variables--diabetes, hypertension, magnitude of ST segment depression, and exercise rate-pressure product-were found to be independent predictors of 3VLMD. In the training population, the prevalence of 3VLMD in low-, intermediate- and high-risk groups was 15%, 22% and 51%, respectively. When the multivariate model was applied to the validation population, the eight-year overall survival rates in the low-, intermediate- and high-risk groups were 89%, 73% and 75%, respectively (p < 0.001)., Conclusions: A substantial proportion of patients with one abnormal thallium coronary territory have 3VLMD with subsequent divergent outcomes based upon risk stratification by clinical and exercise variables. Consequently, the finding of only a single abnormal coronary territory by thallium-201 perfusion imaging does not necessarily confer a benign prognosis in the absence of consideration of nonimaging variables.

Objectives: This study analyzes the relationship between pacing mode and long-term survival in a large group of very elderly patients (> or = 80 years old)., Background: The relationship between pacing mode and long-term survival is not clear. Because the number of very elderly who are candidates for pacing is increasing, issues related to pacemaker (PM) use in the elderly have important clinical and economic implications., Methods: We retrospectively reviewed 432 patients (mean age, 84.5+/-3.9 years) who received their initial PM (ventricular in 310 and dual chamber in 122) between 1980 and 1992. Follow-up was complete (3.5+/-2.6 years). Observed survival was estimated by the Kaplan-Meier method. Age- and gender-matched cohorts from the Minnesota population were used for expected survival. Log-rank test and Cox regression hazard model were used for univariate and multivariate analyses., Results: Patients with ventricular PMs appeared to have poor overall survival compared with those with dual-chamber PMs. Observed survival after PM implantation in high grade atrioventricular block (AVB) patients was significantly worse than expected survival of the age- and gender-matched population (p < 0.0001), whereas observed survival of patients with sinus node dysfunction was not significantly different from expected survival of the matched population (p = 0.413). By univariate analysis, ventricular pacing in patients with AVB appeared to be associated with poor survival compared with dual-chamber pacing (hazard ratio [HR] 2.08; 95% confidence interval [CI] 1.33 to 3.33). After multivariate analysis, this difference was no longer significant (HR 1.41; 95% CI 0.88 to 2.27). Independent predictors of all-cause mortality were number of comorbid illnesses, New York Heart Association functional class, left ventricular depression and older age at implant. Pacing mode was not an independent predictor of overall survival. Older age at implantation, diabetes mellitus, dementia, history of paroxysmal atrial fibrillation and earlier year of implantation were independent predictors of ventricular pacemaker selection., Conclusions: After PM implantation, long-term survival among very elderly patients was not affected by pacing mode after correction of baseline differences. Selection bias was present in pacing mode in the very elderly, with ventricular pacing selected for sicker and older patients, perhaps partly explaining the apparent "beneficial impact on survival" observed with dual-chamber pacing.

Objectives: This study was conducted to develop a time-efficient tilt table test., Background: Current protocols of tilt table testing are quite time-consuming. This study was designed to assess the diagnostic value, tolerance and procedural time of a single-stage isoproterenol tilt table protocol., Methods: A single-stage isoproterenol tilt table test was compared with the passive tilt table test. The study was prospectively designed in a randomized and crossover fashion., Results: The study population consisted of 111 patients with a history of syncope (mean age 55 +/- 20 years). Of the total, 62 patients (56%; 95% confidence interval, 46% to 65%) had a positive vasovagal response during isoproterenol tilt table testing and 35 (32%; 23% to 41%) during passive tilt table testing (p = 0.002). The mean procedural times of the study population were 11.7 +/- 3.6 min and 36.9 +/- 13.3 min for isoproterenol and passive tilt table testing, respectively (p < 0.001). All patients tolerated single-stage isoproterenol testing. In the 23 control subjects (mean age 34 +/- 11 years), the apparent specificities were 91% (72% to 99%) and 83% (61% to 99%) for passive and single-stage tilt table testing, respectively., Conclusions: The single-stage isoproterenol tilt table test was more effective in inducing a positive vasovagal response in an adult population than the standard passive tilt table test, and it significantly reduced the procedural time. The increase in positive yield was associated with a moderate decrease in apparent specificity. These observations support the conclusion that single-stage tilt table testing could be a reasonable diagnostic option in patients undergoing syncope evaluation.

Objectives: We sought to determine the prognostic capabilities of exercise thallium (Tl)-201 tomographic imaging performed relatively early (within 2 years) after coronary artery bypass graft surgery (CABG)., Background: Exercise testing is commonly performed after CABG, but few data exist demonstrating its prognostic value in this setting., Methods: Four hundred eleven patients were followed up for a median duration of 5.8 years. Eleven prospectively chosen clinical, exercise and Tl-201 variables were tested for their associations with outcome end points by means of proportional hazards regression models., Results: During follow-up there were 60 deaths from any cause, 53 initial cardiac deaths or nonfatal myocardial infarctions (MIs) and 22 late (>3 months after the Tl-201 study) revascularization procedures. The number of abnormal Tl-201 segments on the postexercise image was the only variable in the multivariate analyses to show a significant association with all three outcome end points: chi-square 7.3, p = 0.007 for overall mortality; chi-square 8.1, p = 0.004 for cardiac death or MI; chi-square 7.8, p = 0.005 for any cardiac event. Other independent predictors of outcome were exercise duration (chi-square 10.7, p = 0.001) and age (chi-square 3.9, p = 0.049) for overall mortality and exercise angina score (chi-square 8.7, p = 0.003) for cardiac death or MI. The 5-year survival rate free of cardiac death or MI was 93% for patients without angina and a normal image or small postexercise perfusion defect versus 71% for patients with angina and a medium or large defect., Conclusions: Exercise Tl-201 imaging performed within 2 years of CABG can stratify patients into low and high risk subgroups.

Objectives: This study was designed to determine the clinical value of a Doppler-derived index of combined systolic and diastolic myocardial performance in the assessment of cardiac amyloidosis., Background: Cardiac amyloidosis is an infiltrative disease with diastolic and systolic dysfunction. Therefore, the index of myocardial performance combining systolic and diastolic time intervals could be a useful predictor of clinical outcome in cardiac amyloidosis., Methods: The study included 45 patients with biopsy-proved amyloidosis and 45 age-matched normal subjects. All patients had typical echocardiographic features of amyloid cardiac involvement. A Doppler-derived index, defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time, was measured from left ventricular outflow and mitral inflow Doppler velocity profiles recorded during routine echocardiography. The index as well as conventional systolic or diastolic echocardiographic/Doppler variables were related to subsequent outcome., Results: The isovolumetric contraction and relaxation times were prolonged and ejection time was shortened (p < 0.001) in patients with amyloidosis compared with that in normal subjects, resulting in a marked increase of the index from normal values (p < 0.001). In the amyloid group the index was highest in patients with a low stroke index or with both shortened mitral deceleration time and lower ejection fraction. By univariate analysis, New York Heart Association functional class, the index, ejection fraction and mitral deceleration time were significant predictors of outcome. However, by multivariate stepwise regression analysis, functional class and the index were the only independent predictors of survival., Conclusions: The Doppler-derived index of combined systolic and diastolic myocardial performance correlates with global cardiac dysfunction and is a useful predictor of clinical outcome in patients with cardiac amyloidosis.

Objectives: The purpose of this study was to use intravascular ultrasound to determine the morphologic appearance of the coronary arteries, relating the absence, presence and extent of atherosclerosis to the response of the coronary arteries to acetylcholine infusion., Background: Endothelial function plays a major role in the pathophysiology of myocardial ischemia and angina pectoris. The response of the coronary arteries to selective infusion of acetylcholine has been used to examine endothelial function, with vasoconstriction occurring in the absence of intact endothelial function. Vasoconstriction to acetylcholine infusion in humans without overt coronary artery disease has been attributed to early atherosclerosis not detected by coronary angiography., Methods: Twenty-nine patients without overt coronary artery disease underwent selective coronary angiography and selective intracoronary infusion of increasing concentrations of acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter), followed by intravascular ultrasound imaging., Results: The response of the coronary arteries to acetylcholine infusion was not dependent on the absence or presence of atherosclerotic plaque, as detected by intravascular ultrasound. The percent change in epicardial coronary artery diameter during acetylcholine infusion versus baseline was -14 +/- 28% (mean +/- SD) in the seven patients with no visible atherosclerosis on intravascular ultrasound versus -9 +/- 20% in the 22 patients with visible atherosclerosis on intravascular ultrasound (p = NS, confidence interval -14% to 25%). There was a greater vasoconstrictive response to acetylcholine infusion in patients with risk factors for coronary artery disease than in those without risk factors (p = 0.003)., Conclusions: The vasoreactive response to acetylcholine is not necessarily dependent on ultrasound detection of the presence or absence of atherosclerosis.

Objectives: The purpose of this study was to estimate the effect of an improved reperfusion therapy for acute myocardial infarction on myocardial salvage and ventricular function for anterior and inferior infarctions and to ascertain the sample size required to detect such an effect., Background: There are significant differences in myocardium at risk between anterior and inferior infarctions that affect the benefit of reperfusion therapy., Methods: We studied 58 patients with acute myocardial infarction (24 anterior, 34 inferior) treated with intravenous recombinant tissue-type plasminogen activator and angioplasty when necessary. Tomographic imaging with technetium-99m sestamibi was performed to measure myocardium at risk, final infarct size and myocardial salvage and to estimate the beneficial effects of an improved therapy., Results: A new therapy that was 30% more effective than existing therapy (with respect to salvage) would increase salvage (and reduce mean infarct size) by 5.2% of the left ventricle and increase late ejection fraction by only 0.012 (95% confidence interval [CI] 0.009 to 0.015) in inferior infarction and by 0.038 (95% CI 0.027 to 0.047) in anterior infarction. If anterior and inferior infarctions occurred with equal frequency, a sample size of 140 patients in each treatment group would be required to detect such a change with 80% power. In a trial of interior infarctions alone, a sample size of 236 patients in each treatment group would be required compared with only 98 patients in a trial of anterior infarctions alone., Conclusions: The anticipated mean benefit from an improved reperfusion therapy in individual patients with inferior infarction is very small and of questionable clinical significance. The anticipated benefit in anterior infarction is greater and easier to detect. Future randomized trials should be stratified for infarct location and should consider the greater absolute benefit of treatment in anterior infarction.