Fredric J. Pashkow

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.

Accuracy and limitations of exercise echocardiography in a routine clinical setting

Despite the high reported accuracy of exercise echocardiography in the detection of coronary artery disease, factors that compromise its sensitivity and specificity are less clear. This study examined the results of 179 post-treadmill stress echocardiograms in 150 consecutive patients who also underwent cardiac catheterization and in 29 normal persons at low risk for coronary artery disease. Of 114 patients who had significant coronary stenoses at angiography, 96 had an abnormal exercise echocardiogram (overall sensitivity 84%). False negative results correlated with the performance of submaximal exercise, single-vessel disease and moderate (50% to 70% diameter) stenoses. After the exclusion of seven patients performing submaximal exercise, the sensitivity was 90%. In 54 patients without previous infarction performing maximal exercise, the sensitivity was 87%, higher in patients with multivessel coronary disease (96%) than in those with single-vessel disease (79%). After the exclusion of patients with nondiagnostic results, due either to the performance of submaximal stress or the presence of electrocardiographic (ECG) changes at rest, exercise echocardiography had a higher sensitivity than did exercise electrocardiography (87% vs. 63%, p = 0.01). In 36 patients without significant coronary disease, exercise echocardiography had an overall specificity of 86%. After the exclusion of patients with a nondiagnostic test, exercise echocardiography had a specificity of 82% compared with 74% specificity for exercise electrocardiography (p = NS). Similarly, of the 29 normal subjects, 93% had a normal exercise echocardiogram and 97% had a normal exercise ECG (p = NS). Similarly, of the 29 normal subjects, 93% had a normal exercise echocardiogram and 97% had a normal exercise ECG (p = NS). Age, gender, body weight and image quality did not significantly influence the accuracy of exercise echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women

OBJECTIVES This study compared the accuracy and cost implications of using exercise echocardiography and exercise electrocardiography for detection of coronary artery disease in women. BACKGROUND The specificity of exercise electrocardiography in women is lower than in men. Exercise echocardiography accurately identifies coronary artery disease in women, but its utility in place of exercise electrocardiography is unclear. METHODS One hundred sixty-one women without a previous Q wave infarction underwent exercise echocardiography and coronary angiography. Positive findings were a new or worsening wall motion abnormality on the exercise echocardiogram and ST segment depression > 0.1 mV at 0.08 s after the J point on the exercise electrocardiogram (ECG). RESULTS Coronary artery stenosis > 50% diameter narrowing was present in 59 patients; the sensitivity (mean +/- SD) of exercise echocardiography was 80 +/- 3%. In 48 patients with an interpretable ECG, the sensitivity of exercise echocardiography was 81 +/- 4%, and that of the exercise ECG was 77 +/- 3% (p = 0.50). In 102 patients without coronary artery disease, the overall specificity of exercise echocardiography was 81 +/- 4%. In 70 patients with an interpretable ECG, the specificity of exercise echocardiography (80 +/- 3%) exceeded that of the exercise ECG (56 +/- 4%, p < 0.0004). The accuracy of exercise echocardiography was also greater than exercise electrocardiography (81 +/- 5% vs. 64 +/- 6%, p < 0.005). Exercise echocardiography stratified significantly more patients of intermediate (20% to 80%) pretest disease probability into the high (> 80%) or low (< 20%) posttest probability group. In women without a previous exercise ECG, the specificity of exercise echocardiography continued to exceed that of exercise electrocardiography (80 +/- 3% vs. 64 +/- 3%, p = 0.05). Exercise echocardiography had the best balance between accuracy and cost for the diagnosis of coronary artery disease in women. CONCLUSIONS Exercise echocardiography is more specific than exercise electrocardiography for diagnosis of coronary artery disease in women and is a cost-effective approach to the diagnosis of coronary artery disease because of the avoidance of inappropriate angiography.

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.

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.

Issues in contemporary cardiac rehabilitation: A historical perspective

Cardiac rehabilitation consists of exercise, psychosocial support and education and is prescribed most often for patients with coronary heart disease. Its purpose is to facilitate readaptation to normal life through the achievement of maximal functional capability and to reduce heart disease risk factors. It began historically with progressive ambulation after myocardial infarction and by 1980 became a standardized inpatient therapy performed according to a stepped procedure. Predischarge exercise testing was added and has become a meaningful contribution to the concept of risk stratification after an acute coronary event. Rehabilitation has subsequently become part of the outpatient environment and is delivered by multiple models. Meta-analyses have shown that rehabilitation reduces overall and cardiovascular deaths by about 20% and sudden death by about 37% during the year after an acute myocardial infarction. The significance of this, however, must now be modulated by the dynamic role of aggressive coronary intervention. Selection for such intervention has become an important adjunctive aspect of rehabilitation. Newer findings suggest that those stratified at low risk will benefit most by the modification of coronary risk factors, and that patients previously thought to be poor candidates for rehabilitation (such as those with significant left ventricular dysfunction and low work capacity) may experience substantial relative functional benefit. Beyond risk stratification, important contemporary issues include surveillance of patients after angioplasty, the effectiveness of rehabilitation in the attenuation or reversal of both native and vein graft atherosclerosis and consideration of such currently emphasized end points as quality of life and economic evaluation.

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.

Delayed systolic blood pressure recovery after graded exercise: An independent correlate of angiographic coronary disease

OBJECTIVE This study was performed to determine whether a delayed decline in systolic blood pressure (SBP) after graded exercise is an independent correlate of angiographic coronary disease. BACKGROUND The predictive importance of the rate of SBP decline after exercise relative to blood pressure changes during exercise has not been well explored. METHODS Among adults who underwent symptom-limited exercise treadmill testing and who underwent coronary angiography within 90 days, a delayed decline in SBP during recovery was defined as a ratio of SBPs at 3 min of recovery to SBP at 1 min of recovery >1.0. Severe angiographic coronary artery disease was defined as left main disease, three-vessel disease or two-vessel disease with involvement of the proximal left anterior descending artery. RESULTS There were 493 subjects eligible for analyses (age 59 +/- 11 years, 78% male). Severe angiographic coronary disease was noted in 102 (21%). There were associations noted between a delayed decline in SBP during recovery and severe angiographic coronary disease (34% vs. 17%, odds ratio [OR] 2.59, confidence interval [CI] 1.58 to 4.25, p = 0.001). In multivariate logistic regression analyses adjusting for SBP changes during exercise and other potential confounders, a delayed decline in SBP during recovery remained predictive of severe angiographic coronary disease (adjusted OR 2.22, 95% CI 1.27 to 3.87, p = 0.005). CONCLUSIONS A delayed decline in SBP during recovery is associated with a greater likelihood of severe angiographic coronary disease even after accounting for the change in SBP during exercise.

Cardiac Rehabilitation Participation Patterns in a Large, Tertiary Care Center: Evidence for Selection Bias

BACKGROUND Clinical practice guidelines have been published for cardiac rehabilitation, directing programs to address secondary risk-reduction issues. The role of risk factor profiles in the referral of patients to cardiac rehabilitation programs has not been evaluated. METHODS Patients from the Cardiovascular Information Registry at the Cleveland Clinic Foundation (CCF) who entered the CCF hospital-based cardiac rehabilitation program (n = 371) were compared with those who did not participate in the CCF program (n = 2960) with respect to gender, demographics, and risk factor profile for CAD. A random subset of those who did not participate in the CCF program (n = 100) was interviewed by phone to determine participation patterns in other rehabilitation programs. RESULTS Only 11% of patients participated in CCF-based program. Standard risk factors were similar between participants and nonparticipants. Rehabilitation patients were younger (63 +/- 10 versus 66 +/- 10, P < 0.01) and as a group had better left ventricular function (moderate-severe left ventricle: 16% versus 23%, P < 0.01) than nonparticipants. Women were underrepresented in the CCF rehabilitation population (20% versus 30%, P < 0.01). Of the phone survey sample, 21% of patients entered other community-based rehabilitation programs. Similar trends with respect to risk factors, younger age, and better left ventricular function were noted for the community subset. However, women accounted for a greater percentage of the participants in the community programs than the CCF-based program (42.8% versus 19.7%, P < 0.03). CONCLUSIONS Conclusions based on institution-specific programs likely underestimate overall participation in cardiac rehabilitation. Traditional risk factors apparently are not considered when referring patients to cardiac rehabilitation programs. Younger patients with lower mortality risks preferentially participate in rehabilitation programs. Women are more likely to participate in community-based programs. Overall use of cardiac rehabilitation programs remains low.