Claire E Snader

Heart-rate recovery immediately after exercise as a predictor of mortality.

BACKGROUND The increase in heart rate that accompanies exercise is due in part to a reduction in vagal tone. Recovery of the heart rate immediately after exercise is a function of vagal reactivation. Because a generalized decrease in vagal activity is known to be a risk factor for death, we hypothesized that a delayed fall in the heart rate after exercise might be an important prognostic marker. METHODS For six years we followed 2428 consecutive adults (mean [+/-SD] age, 57+/-12 years; 63 percent men) without a history of heart failure or coronary revascularization and without pacemakers. The patients were undergoing symptom-limited exercise testing and single-photon-emission computed tomography with thallium scintigraphy for diagnostic purposes. The value for the recovery of heart rate was defined as the decrease in the heart rate from peak exercise to one minute after the cessation of exercise. An abnormal value for the recovery of heart rate was defined as a reduction of 12 beats per minute or less from the heart rate at peak exercise. RESULTS There were 213 deaths from all causes. A total of 639 patients (26 percent) had abnormal values for heart-rate recovery. In univariate analyses, a low value for the recovery of heart rate was strongly predictive of death (relative risk, 4.0; 95 percent confidence interval, 3.0 to 5.2; P<0.001). After adjustments were made for age, sex, the use or nonuse of medications, the presence or absence of myocardial perfusion defects on thallium scintigraphy, standard cardiac risk factors, the resting heart rate, the change in heart rate during exercise, and workload achieved, a low value for heart-rate recovery remained predictive of death (adjusted relative risk, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). CONCLUSIONS A delayed decrease in the heart rate during the first minute after graded exercise, which may be a reflection of decreased vagal activity, is a powerful predictor of overall mortality, independent of workload, the presence or absence of myocardial perfusion defects, and changes in heart rate during exercise.

Ventilatory and Heart Rate Responses to Exercise: Better Predictors of Heart Failure Mortality Than Peak Oxygen Consumption

BACKGROUND An abnormally low chronotropic response and an abnormally high ventilatory response (V(E)/V(CO2)) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. METHODS AND RESULTS Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V(O2) and V(E)/V(CO2) were directly measured. Chronotropic index and peak V(O2) were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V(E)/V(CO2) was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V(E)/V(CO2) low chronotropic index, low V(O2), low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V(E)/V(CO2) and peak V(O2), it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V(E)/V(CO2) (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). CONCLUSIONS The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.

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.

Complete bundle branch block as an independent predictor of all-cause mortality: report of 7,073 patients referred for nuclear exercise testing.

Abstract PURPOSE: Complete left bundle branch block is a well-established independent risk factor for mortality, but the prognostic importance of right bundle branch block is unclear. We determined whether left and right bundle branch block was associated with all-cause mortality risk after adjustment for potential confounders, including clinical, exercise, and nuclear scintigraphic variables. SUBJECTS AND METHODS: We studied 7,073 adults who were referred for symptom-limited nuclear exercise testing. Patients with heart failure or pacemakers were excluded. The presence or absence of bundle branch block was determined from resting electrocardiograms. The main outcome measure was all-cause mortality during a mean of 6.7 years of follow-up. RESULTS: One hundred ninety patients (3%) had complete right bundle branch block, and 150 (2%) had complete left bundle branch block. There were 825 deaths (12%). Mortality was greater in patients with complete right bundle branch block (24% [46 of 190]) or left bundle branch block (24% [36 of 150]) than in those without these findings (11% [779 of 6,883 and 789 of 6,923, respectively]; both P P = 0.007) as left bundle branch block (HR 1.5; 95% CI: 1.0 to 2.0; P = 0.017). Incomplete right bundle branch block was not associated with mortality. CONCLUSION: Complete right and left bundle branch block are independent predictors of all-cause mortality risk even after adjustment for exercise capacity, nuclear perfusion defects, and other risk factors.

Prediction of death and myocardial infarction by screening with exercise-thallium testing after coronary-artery-bypass grafting.

BACKGROUND The role of myocardial-perfusion imaging in calculating risk in symptom-free patients who have had coronary-artery-bypass grafting (CABG) is unclear. Practice guidelines have argued against routine screening of these patients. We sought to find out the independent and incremental prognostic value of exercise thallium-201 single-photon-emission computed tomography (SPECT) for prediction of death and non-fatal myocardial infarction (MI) in these patients. METHODS Analyses were based on 873 symptom-free patients undergoing symptom-limited exercise thallium-201 SPECT between September, 1990, and December, 1993. All had undergone CABG and none had recurrent angina or other major intercurrent coronary events. Exercise and thallium-perfusion variables were analysed to determine their prognostic importance during 3 years of follow-up. FINDINGS Myocardial-perfusion defects were noted in 508 (58%) patients. There were 57 deaths and 72 patients had major events (death or non-fatal MI). Patients with thallium-perfusion defects were more likely to die (9% vs 3%, p=0.0004) or suffer a major event (11% vs 4%, p=0.0002). Reversible defects were also predictive of death (12% vs 5%, p=0.002) and major events (13% vs 7%, p=0.004). The exercise variable with the strongest predictive power was an impaired (< or = 6 METs [measure of oxygen consumption equal to 3.5 mL/kg/min]) exercise capacity; poor exercise capacity was predictive of death (18% vs 4%, p<0.0001) and death or non-fatal MI (19% vs 5%, p<.00001). After adjusting for baseline clinical variables, surgical variables, time elapsed since CABG, and standard cardiovascular risk factors, thallium-perfusion defects remained predictive of death (adjusted relative risk 2.78, 95% CI 1.44-5.39) and major events (2.63, 1.49-4.66). Similarly, impaired exercise remained strongly predictive of death (4.16, 2.38-7.29) and major events (3.61, 2.22-5.87) after adjusting for confounders. INTERPRETATION In this group of patients who were symptom-free after CABG, thallium-perfusion defects and impaired exercise capacity were strong and independent predictors of subsequent death or non-fatal MI. Recommendations against routine screening exercise myocardial-perfusion studies in this setting should be reconsidered.

Usefulness of impaired chronotropic response to exercise as a predictor of mortality, independent of the severity of coronary artery disease.

Chronotropic incompetence, or an attenuated heart rate response to exercise, has been shown to be associated with an adverse outcome. It is not known whether chronotropic incompetence predicts all-cause mortality independent of angiographic severity of coronary artery disease (CAD). Study subjects included consecutive patients who underwent first-time, symptom-limited exercise treadmill testing and coronary angiography within 90 days; no patient was taking beta blockers or had a history of heart failure, valve disease, or prior revascularization. Chronotropic response was measured in 2 ways: (1) failure to reach 85% of the age-predicted maximum heart rate, and (2) a low chronotropic index, a measure of exercise heart rate response that accounts for effects of age, physical fitness, and resting heart rate. Angiographic severity of CAD was assessed using the Duke Prognostic Weight Score, with a score > or = 42 considered to be indicative of severe CAD. Among 384 eligible patients, failure to reach 85% of the age-predicted maximum heart rate occurred in 61 (16%) and a low chronotropic index was noted in 133 (35%). Severe CAD was present in 63 (16%). During 6 years of follow-up there were 56 deaths. Mortality was predicted by failure to reach target heart rate (RR 1.85, 95% confidence interval [CI] 1.01 to 3.39, chi-square = 4, p = 0.05), by severe CAD (RR 2.21, 95% CI 1.24 to 3.95, chi-square = 8, p = 0.007), and, most strongly, by a low chronotropic index (RR 2.72, 95% CI 1.60 to 4.61, chi-square = 15, p = 0.0002). In a multivariable model, low chronotropic index remained predictive of death (adjusted RR 2.22, 95% CI 1.29 to 3.82, p = 0.004), whereas severe CAD no longer predicted death (adjusted RR 1.27, 95% CI 0.70 to 2.31, p > 0.4). Thus, chronotropic incompetence is a strong and independent predictor of death, even after accounting for the angiographic severity of CAD.

Independent contribution of myocardial perfusion defects to exercise capacity and heart rate recovery for prediction of all-cause mortality in patients with known or suspected coronary heart disease ☆

OBJECTIVES The goal of this study was to determine the value of thallium201 single photon emission computed tomography (SPECT) imaging for prediction of all-cause mortality when considered along with functional capacity and heart rate recovery. BACKGROUND Myocardial perfusion defects identified by thallium201 SPECT imaging are predictive of cardiac events. Functional capacity and heart rate recovery are exercise measures that also have prognostic implications. METHODS We followed 7,163 consecutive adults referred for symptom-limited exercise thallium SPECT (mean age 60 +/- 10, 25% women) for 6.7 years. Using information theory, we identified a probable best model relating nuclear findings to outcome to calculate a prognostic nuclear score. RESULTS There were 855 deaths. Intermediate- and high-risk prognostic nuclear scores were noted in 28% and 10% of patients. Compared with those with low-risk scans, patients with an intermediate-risk score were at increased risk for death (14% vs. 9%, hazard ratio: 1.67, 95% confidence interval [CI]: 1.44 to 1.95, p < 0.0001), while those with high-risk scores were at greater risk (24%, hazard ratio: 2.98, 95% CI: 2.49 to 3.56, p < 0.0001). In multivariable analyses that adjusted for clinical characteristics, functional capacity and heart rate recovery, an intermediate-risk nuclear score remained predictive of death (adjusted hazard ratio: 1.50, 95% CI: 1.28 to 1.76, p < 0.0001), as did a high-risk score (adjusted hazard ratio: 2.76, 95% CI: 2.13 to 2.56, p < 0.0001). Impaired functional capacity and decreased heart rate recovery provided additional prognostic information. CONCLUSIONS Myocardial perfusion defects detected by thallium SPECT imaging are independently predictive of long-term all-cause death, even after accounting for exercise capacity, heart rate recovery and other potential confounders.

Coronary Risk Prediction by Logical Analysis of Data

The objective of this study was to distinguish within a population of patients with known or suspected coronary artery disease groups at high and at low mortality rates. The study was based on Cleveland Clinic Foundations dataset of 9454 patients, of whom 312 died during an observation period of 9 years. The Logical Analysis of Data method was adapted to handle the disproportioned size of the two groups of patients, and the inseparable character of this dataset – characteristic to many medical problems. As a result of the study, we have identified a high-risk group of patients representing 1/5 of the population, with a mortality rate 4 times higher than the average, and including 3/4 of the patients who died. The low-risk group identified in the study, representing approximately 4/5 of the population, had a mortality rate 3 times lower than the average. A Prognostic Index derived from the LAD model is shown to have a 83.95% correlation with the mortality rate of patients. The classification given by the Prognostic Index was also shown to agree in 3 out of 4 cases with that of the Cox Score, widely used by cardiologists, and to outperform it slightly, but consistently. An example of a highly reliable risk stratification system using both indicators is provided.

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.

Value of Exercise Capacity and Heart Rate Recovery in Older People

OBJECTIVES: To evaluate the prognostic value in older adults of two predictors of mortality: impaired functional capacity and an attenuated heart rate recovery.