Sharon A. Harvey

Importance of estimated functional capacity as a predictor of all-cause mortality among patients referred for exercise thallium single-photon emission computed tomography: report of 3,400 patients from a single center.

OBJECTIVES We sought to determine the relative influence of estimated functional capacity and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) findings on prediction of short-term all-cause and cardiac-related mortality. BACKGROUND Decreased functional capacity and abnormal Tl-201 SPECT findings are predictive of increased cardiovascular risk and mortality. However, the relative importance of these variables as predictors of all-cause mortality is not well established. METHODS Analyses were based on 3,400 consecutive adults undergoing symptom-limited exercise Tl-201 SPECT testing at the Cleveland Clinic Foundation between September 1990 and December 1993; none had previous invasive procedures, heart failure or valve disease. Estimated functional capacity, classified by age and gender, and thallium perfusion defects, expressed as a stress extent thallium score on a 12-segment scale, were analyzed to determine their relative prognostic importance during 2 years of follow-up. RESULTS Of 3,400 patients, 108 (3.2%) died during follow-up; 32 deaths were identified as cardiac related. On univariable analysis, estimated functional capacity was a strong predictor of death, with 62 (57%) deaths occurring in patients achieving < 6 metabolic equivalents (METs) (log-rank chi-square 86, p < 0.0001). On multivariable analysis, the strongest independent predictors of all-cause mortality were fair or poor functional capacity (adjusted relative risk [RR] 3.96, 95% confidence interval [CI] 2.36 to 6.64, chi-square 27, p < 0.0001) and age (adjusted RR for 10 years 2.25, 95% CI 1.80 to 2.80, chi-square 27, p < 0.0001). The presence of SPECT thallium perfusion defects was a less powerful predictor of death (for each two additional segments with defects, adjusted RR 1.21, 95% CI 1.03 to 1.43, chi-square 5, p = 0.02). Cardiac mortality was predicted by both fair or poor functional capacity (adjusted RR 4.37, 95% CI 1.59 to 12.00, chi-square 8, p = 0.004) and by stress extent thallium score (adjusted RR 1.62, 95% CI 1.25 to 2.11, chi-square 13, p = 0.0003). CONCLUSIONS In this clinically low risk group, estimated functional capacity was a strong and overwhelmingly important independent predictor of all-cause mortality among patients undergoing exercise Tl-201 SPECT testing. The extent of myocardial perfusion defects was of comparable importance for the prediction of cardiac mortality.

Gender and Referral for Coronary Angiography After Treadmill Thallium Testing

Considerable controversy exists regarding whether women are less likely than men to be referred to coronary angiography after an abnormal noninvasive test. This prospective cohort study analyzed consecutive subjects (2,351 men and 1,318 women) with no prior history of invasive cardiac procedures who were referred for treadmill thallium testing at the Cleveland Clinic Foundation. The primary end point was performance of coronary angiography within 90 days of treadmill thallium testing. A secondary end point was all-cause mortality during 1.8 years of follow-up. Women were less likely than men to undergo coronary angiography (6% vs 14%, odds ratio [OR] 0.42, 95% confidence interval [Cl] 0.33 to 0.54, p < 0.001), but were also less likely to have an abnormal thallium scan (8% vs 29%, p < 0.001). In logistic regression analyses with adjustment for thallium result and age, women were as likely as men to be referred for coronary angiography (adjusted OR 1.00, 95% Cl 0.75 to 1.34, p > 0.9). Women were less likely to have severe coronary disease on angiography (15% vs 30%, p = 0.006). During 1.8 years of follow-up there were 26 deaths (2%) among women and 84 deaths (4%) among men. After adjusting for age, thallium abnormalities, and clinical characteristics in Cox regression analyses, women had a lower mortality rate than men (relative risk 0.58, 95% Cl 0.36 to 0.94, p = 0.03). Thus, gender-related differences in referral for coronary angiography after treadmill thallium testing can be explained by a higher rate of abnormal tests in men. No evidence of a post-test gender bias was detected, but a pretest bias affecting referral to nuclear testing cannot be excluded. Furthermore, women have a lower prevalence of severe coronary disease and a lower adjusted mortality rate.

Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease.

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as > or = 1 stenosis of > or = 50% in a major epicardial artery or its main branches; severe coronary disease was defined as > or = 50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with > or = 70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.

Sex and diagnostic evaluation of possible coronary artery disease after exercise treadmill testing at one academic teaching center

Controversy exists as to whether a sex bias exists that affects the diagnostic approach to suspected coronary artery disease: previous studies have used coronary angiography, but not other noninvasive testing, as a primary end point. This investigation examined posttest sex differences in diagnostic evaluation after exercise treadmill testing according to a broader end point than just coronary angiography alone. The design was a cohort analytic study with a 90-day follow-up. The study was done at the Cleveland Clinic Foundation, an academic group practice. Patients included consecutive adults (1023 men and 579 women) with chest pain but no documented coronary disease who were referred for symptom-limited exercise treadmill testing without adjunctive imaging; none had undergone prior invasive cardiac procedures. Main outcome measures included (1) performance of any subsequent diagnostic study (invasive or noninvasive) and (2) performance of coronary angiography as the next diagnostic study. During follow-up, 89 (8.7%) men and 48 (8.3%) women underwent a second diagnostic study (odds ratio 0.95; 95% confidence interval 0.66 to 1.37; p > 0.8), whereas 64 (6.3%) men and 21 (3.6%) women went straight to coronary angiography (odds ratio 0.56; 95% confidence interval 0.34 to 0.93; p = 0.02). In multivariable logistic regression analyses, which considered baseline clinical characteristics, the ST-segment response, and other prognostically important exercise responses, women tended to be less likely than men to be referred to any second test (adjusted odds ratio 0.70; 95% confidence interval 0.42 to 1.19; p > 0.1) but were markedly and significantly less likely to be referred straight to coronary angiography (adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.65). After exercise treadmill testing, women were only slightly less likely than men to be referred for subsequent diagnostic testing; they were, however, much less likely to be referred straight to coronary angiography as opposed to another noninvasive study.

Age and referral to coronary angiography after an abnormal treadmill thallium test

This study investigated the association between age and referral to coronary angiography among ambulatory adults with an abnormal treadmill thallium scan. The subjects studied were 416 consecutive adults who were > or = 30 years old, under the care of cardiologists, and had an abnormal treadmill thallium scan between 1990 and 1993 at the Cleveland Clinic Foundation. The primary end point was performance of coronary angiography within 90 days of the treadmill test. Coronary angiography was performed in 163 subjects. Coronary angiography was performed in 46% of patients aged 30-49 years, in 53% of those aged 50 to 64 years, in 33% of those aged 65 to 74 years, and in only 18% of those aged > or = 75 years (chi2 test for trend, p < 0.0001). After adjustment for potential confounders, age remained associated with a lower rate of referral to angiography (p < 0.0001). During 2 years of follow-up 34 deaths occurred (14 cardiac), with particularly high mortality rates among those aged >74 years (cumulative rate 31%, 95% confidence interval 16% to 47%). The number of abnormal thallium scan segments was predictive of death (p = 0.02). These data suggest that increasing age is associated with a lower rate of referral to coronary angiography after an abnormal treadmill thallium test.