Usefulness of improvement in walking distance versus peak oxygen uptake in predicting prognosis after myocardial infarction and/or coronary artery bypass grafting in men

Information is limited on the influence of a change in fitness and/or physical activity on mortality in cardiac patients who undergo exercise rehabilitation. This was studied in 6,956 men (4,713 with myocardial infarctions, 2,243 who underwent coronary bypass surgery) completing a 12-month walking-based training regimen and followed for a median of 9 years (range 4 to 26; 67,820 patient-years). Peak oxygen uptake (VO2peak) was measured at the beginning and the end of the program, and walking distance and pace were recorded weekly. These and other pertinent data were entered into a Cox proportional-hazards model and tested for associations with time to cardiac and all-cause death. In total, 2,016 deaths were recorded (737 cardiac, 1,279 all-cause). The mean increase in VO2peak was 4.9 ml/kg/min (95% confidence interval [CI] 4.7 to 5.0, p <0.0001), and the mean increase in distance walked was 2.1 mi (95% CI 2.0 to 2.1, p <0.0001). Increase in VO2peak was significant on univariate analysis (hazard ratio [HR] 0.98) but not on multivariate analysis. Distance increase was a significant predictor of cardiac and all-cause death on multivariate analysis, with each 1-mi improvement conferring a 20% reduction in cardiac death (HR 0.80, 95% CI 0.71 to 0.87, p <0.0001). When categorized into groups of <1.3 (referent), 1.3 to 2.8, and >2.8 mi, increased walking distance of 1.3 to 2.8 and of >2.8 mi yielded 24% (HR 0.76, 95% CI 0.62 to 0.92, p = 0.005) and 48% (HR 0.52, 95% CI 0.40 to 0.68, p <0.0001) reductions in cardiac death, respectively. In conclusion, in men who underwent an exercise rehabilitation program, improvement in walking distance was a strong independent predictor, and a greater guide to prognosis, than gains in VO2peak.     

Submaximal effort tolerance as a predictor of all-cause mortality in patients undergoing cardiac rehabilitation

BACKGROUND: Submaximal effort tolerance is routinely available during cardiac rehabilitation, but its prognostic value in relation to underlying referral diagnosis is not known. HYPOTHESIS: Treadmill effort capacity during submaximal exercise training predicts all-cause mortality after cardiac rehabilitation. METHODS: We followed 600 consecutive patients (450 men and 150 women, mean age 65 years) who were referred to a 12-week outpatient program of cardiac rehabilitation; 37% had a prior myocardial infarction (MI), 44% had a recent percutaneous intervention (PCI), and 39% had history of coronary artery bypass surgery (CABG). RESULTS: There were 48 deaths during a mean follow-up period of 1603 +/- 822 days. By multivariate Cox analysis, exit MET activity was the most significant predictor of all-cause mortality. In this model, each 1 MET increase in exit submaximal effort tolerance was associated with a 34% decrease in mortality (hazard ratio [HR] 0.66, 95% confidence interval 0.56-0.77) alone and 28% decrease after adjustment for age (HR = 0.72, confidence interval 0.60-0.85). Enty MET level also had predictive value. Subgroup analysis revealed that the predictive value of exit METs was limited to patients after recent CABG and with MI. None of the variables predicted death after PCI, in whom mortality was significantly lower than in the other groups. CONCLUSIONS: Submaximal effort tolerance at completion of cardiac rehabilitation, and also at entry, is a strong and age-independent predictor of mortality in patients who have had either recent CABG or MI without intervention, but not in patients after recent PCI.     

Peak exercise cardiac power output; a direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure.

OBJECTIVES: This study assessed the prognostic value of peak cardiac power output, measured non-invasively during maximal cardiopulmonary exercise testing, against other exercise-derived haemodynamic variables in patients with chronic congestive heart failure. METHOD AND RESULTS: Two hundred and nineteen unselected, consecutive patients with congestive heart failure (166 men, mean (+/-SD) age of 56+/-13 years) who underwent maximal symptom limited cardiopulmonary treadmill exercise testing with non-invasive estimation of cardiac output using carbon dioxide re-breathing techniques, were followed-up for a mean period of 4.64 (4.47--4.82, 95% CI) years. Cardiac power output was calculated from the product of cardiac output and mean arterial blood pressure. All cause mortality was 12.3% (27 deaths). Peak and resting cardiac power output, peak mean arterial blood pressure, peak and resting cardiac output and peak VO(2)were all predictive of outcome on univariate analyses. Peak cardiac power output, either entered continuously or categorically with a cut-off value of 1.96 watts, was the only independent predictor of mortality (P=0.0004 for values < or >1.96 watts and P=0.001 for continuous values) using multivariate analysis. A relative risk ratio of 5.08 (1.94-13.3, 95% CI) was obtained for a cardiac power output <1.96 watts. CONCLUSION: Peak cardiac power output is an independent predictor of mortality that can be measured non-invasively using cardiopulmonary exercise testing. It can give further prognostic power to a peak VO(2)in the assessment of patients with congestive heart failure.     

The incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: superiority over 85% of maximal age-predicted heart rate

OBJECTIVES: We sought to determine whether chronotropic incompetence (CI) adds incremental value in predicting cardiac death (CD) and all-cause mortality and to determine which marker of CI is superior. BACKGROUND: Chronotropic incompetence, defined by either a low percent heart rate (HR) reserve achieved or failure to achieve 85% maximal age-predicted heart rate (MA-PHR), is a predictor of mortality. These variables have not been examined together in a comprehensive myocardial perfusion single-photon emission computed tomographic (SPECT), or MPS, model. METHODS: A total of 10,021 patients who underwent exercise MPS, evaluated by a summed stress score (SSS), were followed up for 719 +/- 252 days. Percent HR reserve = (peak HR - rest HR)/(220 - age - rest HR) x 100, with <80% considered abnormal. RESULTS: A total of 2,956 patients (29.5%) had low %HR reserve; 1,331 (13.3%) achieved <85% MA-PHR; and 1,296 (13.0%) had both. There were 234 deaths (93 CDs). On multivariate analysis, the SSS, %HR reserve, and inability to achieve 85% MA-PHR were predictors of all-cause mortality and CD (all p < 0.01). Myocardial perfusion SPECT was the most powerful predictor of CD (chi-square = 50). When the %HR reserve and ability to achieve 85% MA-PHR were considered, only the former remained a predictor of CD (p = 0.006 vs. p = 0.59). CONCLUSIONS: In a comprehensive MPS model, CI was an important predictor of CD and all-cause mortality. Percent HR reserve was superior to the ability to achieve 85% MA-PHR in predicting CD; MPS was superior to both. Combined with previous studies, the findings suggest that %HR reserve should become the standard for assessing the adequacy of HR response during exercise testing, and that it should be routinely incorporated in risk stratification algorithms.     

The predictive value of cardiorespiratory fitness for cardiovascular events in men with various risk profiles: a prospective population-based cohort study.

AIMS: Few data exist to show if the prognostic value of peak exercise oxygen consumption (VO2peak) for fatal and non-fatal coronary events is different among men with low and high pre-test probability for cardiovascular disease (CVD). Our objective was to determine whether VO2peak could predict fatal and non-fatal cardiac events in 2361 men aged 42-60 years with and without conventional risk predictors of CVD or with documented CVD during a 13-year follow-up. METHODS AND RESULTS: Maximal oxygen consumption (ml/kg/min) was measured directly by using respiratory gas exchange in a cycle ergometer exercise test. Of 204 CVD deaths, 153 were due to coronary disease and 51 were due to other CVDs. A total of 323 non-fatal coronary events occurred during the follow-up. One metabolic equivalent (MET) increment in VO2peak was related to a decreased risk of coronary death in both healthy (RR=0.82, 95% CI 0.66-0.99) and unhealthy (RR=0.72, 95% CI 0.63-0.82) men. VO2peak was predictive of non-fatal and fatal cardiac events among men with or without known risk factors. In subjects with or without common risk factors, one MET increment amounted to an average decrease of 17-29% in non-fatal and 28-51% in fatal cardiac events, after adjustment for age. VO2peak and smoking represented two strongest independent and consistent risk predictors. CONCLUSIONS: VO2peak can be used as a very powerful predictor of future fatal cardiac events beyond that predicted by many conventional risk factors. On the prognostic consideration, unfit men with unfavourable risk profiles or underlying chronic disease are the risk groups that will benefit most from preventive measures.     

Prognostic value of late heart rate recovery after treadmill exercise

Recovery from exercise can be divided into an early, rapid period and a late, slower period. Although early heart rate (HR) recovery 1 minute after treadmill exercise independently predicts survival, the prognostic value of late HR recovery has not been well studied. The aim of this study was to evaluate the independent prognostic value of late HR recovery for all-cause mortality. A total of 2,082 patients referred to the nuclear cardiology laboratory of an urban academic medical center for treadmill exercise with imaging from August 1998 to December 2003 were followed for all-cause mortality. During 9.9 ± 1.5 years of follow-up, 196 deaths (9%) occurred. To avoid overlap with early HR recovery or the baseline HR, late HR recovery was defined as the percentage of the cycle length change between rest and peak exercise that had been recovered after 5 minutes. Lower values represent impaired recovery, by analogy with 1-minute HR recovery. Impaired late HR recovery was a significant univariate predictor of all-cause mortality (hazard ratio 0.28 per percentage, 95% confidence interval 0.17 to 0.46, p <0.001). It significantly improved a nested, multivariate model (change in chi-square 8.66, p = 0.003), including 1-minute HR recovery, with independent prognostic value (adjusted hazard ratio 0.58, 95% confidence interval 0.41 to 0.84, p = 0.004). In conclusion, late HR recovery after treadmill exercise stress adds prognostic value for all-cause mortality to a multivariate model including early, 1-minute HR recovery.     

Dipyridamole therapy improves long-term survival after complete revascularization in patients with impaired cardiac function

Background Although dipyridamole is no longer used as a mainstream medication for coronary artery disease because of the coronary steal phenomenon, recent studies have shown that the elevation of serum adenosine levels caused by dipyridamole improves cardiac function in heart failure patients. In the present study it was investigated whether use of dipyridamole at the time of complete revascularization affects long-term mortality in patients with impaired left ventricular (LV) function. Methods and Results The 1,836 consecutive patients who underwent complete revascularization between 1984 and 1992 were assessed; 254 patients with impaired LV function (ejection fraction <50%) were enrolled. Cox proportional hazards regression adjusted for baseline covariates and the propensity score were used to compare the risks for mortality between patients who did and did not take dipyridamole. The mean follow-up period was 12 years; 178 patients (70.1%) took dipyridamole and there were 66 (37.1%) all-cause and 22 (12.4%) cardiac deaths in that group. In the multivariate analysis, the dipyridamole group had a lower risk for both all-cause (hazard ratio (HR) 0.54; p=0.005) and cardiac mortality (HR 0.42; p=0.010). Conclusion The use of dipyridamole reduced both all-cause and cardiac mortality in patients with impaired LV function. (Circ J 2008; 72: 1588 - 1593).     

Relation of heart rate parameters during exercise test to sudden death and all-cause mortality in asymptomatic men

Heart rate (HR) profile during exercise predicts all-cause mortality. However, less is known about its relation to sudden (vs nonsudden) death in asymptomatic people. The relation of exercise HR parameters (HR at rest, target HR achievement, HR increase, and HR recovery) with sudden death, coronary heart disease (CHD) death, myocardial infarction, and all-cause mortality was assessed in 12,555 men who participated in MRFIT. Subjects were 35 to 57 years old without clinical CHD, but with higher than average Framingham risk. Trial follow-up was 7 years, and extended follow-up after the trial for all-cause mortality was 25 years. After adjusting for cardiac risk factors, having to stop exercise before achieving 85% of age-specific maximal HR was associated with increased risk of sudden death (hazard ratio 1.8, 95% confidence interval [CI] 1.3 to 2.5, p = 0.001), CHD death (hazard ratio 1.4, 95% CI 1.2 to 1.5, p <0.001), and all-cause mortality (hazard ratio 1.3, 95% CI 1.2 to 1.4, p <0.001). Increased HR at rest (p = 0.001), attenuated HR increase (p = 0.02), delayed HR recovery (p = 0.04), and exercise duration (p <0.0001) were independent predictors of all-cause death in the overall study population and also in the subgroup that achieved target HR. In conclusion, middle-aged men without clinical CHD who stopped exercise before reaching 85% of maximal HR had a higher risk of sudden death. Other exercise HR parameters and exercise duration predicted all-cause mortality.     

The prognostic value of haemodynamic parameters in the recovery phase of an exercise test. The Finnish Cardiovascular Study

We tested the hypothesis that the change from the peak to recovery values of systolic arterial pressure (SAP recovery) and rate-pressure product (RPP recovery) can be used to predict all-cause and cardiovascular mortality, as well as sudden cardiac death (SCD) in patients referred to a clinical exercise stress test. As a part of the Finnish Cardiovascular Study (FINCAVAS), consecutive patients (n=2029; mean age+/-SD=57+/-13 years; 1290 men and 739 women) with a clinically indicated exercise test using a bicycle ergometer were included in the present study. Capacities of attenuated SAP recovery, RPP recovery and heart rate recovery (HRR) to stratify the risk of death were estimated. During a follow-up (mean+/-s.d.) of 47+/-13 months, 122 patients died; 58 of the deaths were cardiovascular and 33 were SCD. In Cox regression analysis after adjustment for the peak level of the variable under assessment, age, sex, use of beta-blockers, previous myocardial infarction and other common coronary risk factors, the hazard ratio of the continuous variable RPP recovery (in units 1000 mm Hg x b.p.m.) was 0.85 (95% CI: 0.73-0.98) for SCD, 0.87 (0.78-0.97) for cardiovascular mortality, and 0.87 (0.81 to 0.94) for all-cause mortality. SAP recovery was not a predictor of mortality. The relative risks of having HRR below 18 b.p.m., a widely used cutoff point, were as follows: for SCD 1.28 (0.59-2.81, ns), for cardiovascular mortality 2.39 (1.34-4.26) and for all-cause mortality 2.40 (1.61-3.58). In conclusion, as a readily available parameter, RPP recovery is a promising candidate for a prognostic marker.     

Long-term prognostic value of peak oxygen consumption in women versus men with heart failure and severely impaired left ventricular systolic function

Although peak oxygen consumption (VO(2)) during exercise is frequently used to help predict optimal timing for heart transplantation, its long-term prognostic value in women is not known. We followed 2,105 adult patients with heart failure (HF) and with impaired left ventricular (LV) systolic function for 5 years, including 525 women (25%) who underwent metabolic stress testing between January 1995 and December 2002. Multivariable proportional hazards modeling related VO(2) to survival with adjustments for >30 confounders and with transplantation considered as a time-dependent covariate. During follow-up, 129 women (26%) died, as did 572 men (36%). There were 175 transplants, including 34 women. Women and men were similar in age (54 vs 55 years), but women were less likely to have coronary artery disease (28% vs 58%). Peak VO(2) was strongly predictive of time to death in women (adjusted hazard ratio [HR] for peak VO(2) decreasing from 15 to 14 ml/kg/min, 1.11, 95% confidence interval [CI] 1.05 to 1.18, p <0.0001) and in men (adjusted HR 1.12, 95% CI 1.08 to 1.16, p <0.0001). There was no gender interaction with peak VO(2) (p = 0.80), but for any given peak VO(2) women were at lower risk (adjusted HR for men compared with women 2.22, 95% CI 1.58 to 3.10, p <0.0001). A significant interaction was found between gender and presence of coronary artery disease (p for interaction 0.02); in women, those with ischemic cardiomyopathy had a worse survival for any given peak VO(2). In conclusion, in this large cohort, peak VO(2) predicted survival in women and men whether or not coronary artery disease was present, but an interaction was noted between coronary artery, gender, and survival.     

Abnormal heart rate recovery after exercise: a comparison with known indicators of increased mortality.

BACKGROUND: Abnormal heart rate (HR) recovery at 1 min after exercise (< or =12 beats) was recently suggested to be a predictor of all cause and cardiac mortality. AIM: This study aimed to (1) correlate HR recovery at 1 min after exercise with known exercise and myocardial perfusion markers of increased cardiac mortality, and (2) compare the known exercise and myocardial perfusion markers of increased cardiac mortality between patients with a normal and abnormal HR recovery at 1 min after exercise. METHODS: One hundred patients with known or suspected coronary artery disease referred for exercise stress testing (ETT) were prospectively enrolled. Percent, ETT time peak HR, HR reserve, summed stress score (SSS), extent of stress (SE%) and reversible perfusion abnormalities (RE%) were recorded in every patient. RESULTS: There was poor correlation with markers of myocardial ischemia or infarction [SSS (r = 0.15), SE% (r = 0.05), RE% (r = 0.12), all p = n.s.] but highly significant correlation between HR recovery at 1 min after exercise and chronotropic variables [ETT time (r = 0.56), peak HR (r = 0.65), HR reserve % (r = 0.64), all p < 0.001]. Patients on beta-blockers had significantly more incidence of an abnormal HR recovery at 1 min after exercise, compared to patients not on beta-blockers (88 vs. 56%, p < 0.01). CONCLUSION: Abnormal HR recovery at 1 min after exercise has no correlation with known myocardial perfusion markers of increased cardiac mortality. Patients with an abnormal HR recovery do not appear to have an increased incidence or more severe myocardial infarction or ischemia. However, there is a strong correlation between HR recovery at 1 min after exercise and the chronotropic variables during exercise.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure

BACKGROUND. Optimal timing of cardiac transplantation in ambulatory patients with severe left ventricular dysfunction is often difficult. To determine whether measurement of peak oxygen consumption (VO2) during maximal exercise testing can be used to identify patients in whom transplantation can be safely deferred, we prospectively performed exercise testing on all ambulatory patients referred for transplant between October 1986 and December 1989. METHODS AND RESULTS. Patients were assigned into one of three groups on the basis of exercise data: Group 1 (n = 35) comprised patients accepted for transplant (VO2 less than or equal to 14 ml/kg/min); group 2 (n = 52) comprised patients considered too well for transplant (VO2 greater than 14 ml/kg/min); and group 3 (n = 27) comprised patients with low VO2 rejected for transplant due to noncardiac problems. All three groups were comparable in New York Heart Association functional class, ejection fraction, and cardiac index (p = NS). Pulmonary capillary wedge pressure was significantly lower in group 2 than in either group 1 or 3 (p less than 0.05), although there was wide overlap. Patients with preserved exercise capacity (group 2) had cumulative 1- and 2-year survival rates of 94% and 84%, which are equal to survival levels after transplantation. In contrast, patients rejected for transplant (group 3) had survival rates of only 47% at 1 year and 32% at 2 years, whereas patients awaiting transplantation (group 1) had a survival rate of 70% at 1 year (both p less than 0.005 versus patients with VO2 greater than 14 ml/kg/min). All deaths in group 2 were sudden. By univariate and multivariate analyses, peak VO2 was the best predictor of survival, with only pulmonary capillary wedge pressure providing additional prognostic information. CONCLUSIONS. These data suggest that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction and peak exercise VO2 of more than 14 ml/min/kg.     

Early heart rate recovery after exercise predicts mortality in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet. METHODS: Ninety-two stable CHF patients (83M/9F, mean age: 51+/-12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %)=(peak HR-resting HR/220-age-resting HR)x100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography. RESULTS: Fatal events occurred in 24 patients (26%) during 21+/-6 months of follow-up. HRR1 was lower in non-survivors (11.4+/-6.4 vs. 20.4+/-8.1; p<0.001). All cause-mortality rate was 65% in patients with HRR112 bpm (log-rank: 32.6; p<0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (chi2=19.2; odds ratio: 0.87; p<0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10-18, ml/kg/min), HRR1 was a strong predictor of mortality (chi2: 14.3; odds ratio: 0.8; p<0.001). CONCLUSIONS: Early heart rate recovery is an independent prognostic risk indicator in CHF patients and could be used in CHF risk stratification.     

Effects of cardiac rehabilitation on exercise capacity in Type 2 diabetic patients with coronary artery disease.

AIM: To determine whether Type 2 diabetic patients with coronary disease can obtain, after cardiac rehabilitation, a similar benefit on exercise capacity to non-diabetic coronary individuals. RESEARCH DESIGN AND METHODS: Fifty-nine Type 2 diabetic patients and 36 age-matched non-diabetic patients were enrolled in a 2-month cardiac rehabilitation programme, after an acute coronary event. At the beginning and at the end of the cardiac rehabilitation programme, each subject underwent a cardiopulmonary exercise test to assess exercise capacity as measured by peak workload, duration of test, maximal heart rate, peak VO2 and anaerobic threshold. The two groups of patients were not different in age, sex ratio, type of coronary event or left ventricular ejection fraction. RESULTS: The baseline exercise capacity parameters were not different between diabetic and non-diabetic subjects. After cardiac rehabilitation, improvement of exercise capacity was significantly less in patients with diabetes compared with those without diabetes: peak workload (19% vs. 29%, P = 0.022), peak VO2 (13% vs. 30%, P = 0.002), anaerobic threshold (12% vs. 31%, P = 0.017). In the diabetic patients, a significant inverse relation between fasting blood glucose and change in peak VO2 was observed on both univariate (r = -0.40, P = 0.002) and multivariate (P = 0.001) analyses. CONCLUSIONS: The benefit of cardiac rehabilitation, after an acute ischaemic heart event, in exercise capacity is significantly lower in Type 2 diabetic patients. The response to cardiac rehabilitation in those with diabetes appears to be influenced by blood glucose levels.     

Ease of noninvasive measurement of cardiac output coupled with peak VO2 determination at rest and during exercise in patients with heart failure

Peak oxygen consumption (VO2) is a powerful prognostic predictor of survival in patients with heart failure (HF) because it provides an indirect assessment of a patient's ability to increase cardiac output (CO). However, many peripheral factors affect VO2. Inert gas rebreathing using low-concentration soluble and insoluble inert gases can derive CO by the Fick principle. The Innocor rebreathing system uses an oxygen-enriched mixture of an inert soluble gas (0.5% nitrous oxide) and an inert insoluble gas (0.1% sulfur hexafluoride) measured by photoacoustic analyzers over a 5-breath interval. The practicality of this device in measuring CO and VO2 during exercise was assessed in patients with HF. Ninety-two consecutive exercise tests were prospectively performed in 88 patients with HF using the Innocor system. Incremental bicycle exercise was performed with CO measurements at rest, at 50 W, and at peak exercise. The mean age of the 68 men and 20 women was 54 +/- 13 years; 33% had coronary artery disease, and 67% had dilated cardiomyopathy. The mean left ventricular ejection fraction was 24 +/- 9%. Patients were able to rapidly learn the rebreathing technique and easily integrate it into the exercise protocol. Eighty-six percent of the tests had successful measurement of metabolic and cardiac output data. Mean CO at rest was 3.5 +/- 1.1 L/min and increased to 7.2 +/- 2.7 L/min. Mean peak VO2 was 12.6 +/- 4.7 ml/kg/min. A significant linear correlation was observed between peak VO2 and peak CO (r = 0.64, p <0.0001). In conclusion, combined metabolic stress testing with inert gas rebreathing can be easily performed in patients with HF.     

Heart rate recovery--a potential marker of clinical outcomes in heart failure patients receiving beta-blocker therapy

BACKGROUND: Heart rate recovery (HRR) within the first few minutes of graded exercise has been associated with impaired clinical outcomes in patients being evaluated for coronary artery disease. HRR is abnormal in patients with heart failure (HF), but has not been associated with clinical outcomes in these patients. The objective of the present study was to determine whether HRR following cardiopulmonary exercise testing (CPET) correlates with peak oxygen consumption (VO(2)), and whether it impacts clinical outcomes, including HF hospitalizations and total mortality, or the need for cardiac transplantation. METHODS: CPET was performed in 78 patients referred to the Montreal Heart Institute (Montreal, Quebec) with congestive HF between January 2000 and December 2002. All patients had New York Heart Association class II or III HF with a left ventricular ejection fraction of 45% or lower. Mean (+/- SD) age was 53+/-11 years and left ventricular ejection fraction was 27+/-9%. Forty-four per cent had ischemic cardiomyopathy, 88% received beta-blockers and 79% received angiotensin-converting enzyme inhibitors. HRR was defined as the difference from peak exercise HR to HR measured at specific time intervals. HRR was calculated 30 s, 60 s, 90 s and 120 s after exercise. RESULTS: Mean peak VO(2) was 18.0+/-5.3 mL/kg/min, resting HR was 74+/-13 beats/min and peak HR was 119+/-22 beats/min. HRR measured was 10+/-9 beats/min after 30 s, 20+/-12 beats/min after 60 s, 25+/-15 beats/min after 90 s and 30+/-13 beats/min after 120 s. At 90 s, patients with an HRR below 24 beats/min were more likely to have an HF hospitalization at five-year follow-up (eight hospitalizations [22.2%] versus two hospitalizations [2.7%]; P=0.0134). There was a correlation between peak VO(2) and HRR 90 s and 120 s after completion of the exercise test (r=0.40 after 90 s, P=0.001, and r=0.41 after 120 s, P=0.008). CONCLUSIONS: In patients with HF, blunted HRR 90 s and 120 s after CPET correlate with peak VO(2) and are associated with increased risk of worsening HF. HRR is easily measured and a useful marker for morbidity in patients with HF.     

Initial and final exercise heart rate transients: influence of gender, aerobic fitness, and clinical status

STUDY OBJECTIVES: To compare the independent and additive data provided by initial and final heart rate (HR) exercise transients, and to analyze both according to gender, aerobic fitness, clinical status, and medication usage. DESIGN: Retrospective study. SETTING: Exercise medicine clinic. PATIENTS: A total of 544 subjects (363 men) with a mean (+/- SD) age of 50 +/- 14 years (age range, 10 to 91 years), including asymptomatic and coronary artery disease patients. MEASUREMENTS AND RESULTS: HR transients were obtained from the following two exercise protocols: 4-s exercise test (4sET) followed by a maximal cardiopulmonary cycling exercise test (CPET). The initial HR transient was represented by the cardiac vagal index (CVI), which was obtained by the 4sET, and the final transient (ie, HR recovery [HRR]) was determined by the following equation: CPET maximal HR - the 1-min postexercise HR. Transients were modestly related (r = 0.22; p < 0.001) when adjusted for age, aerobic fitness, clinical status, and negative chronotropic action drug usage. The transients were unrelated to gender (vs CVI, p = 0.10; vs HRR, p = 0.15). Subjects with a measured maximum oxygen uptake (VO2max) exceeding 100% of the predicted maximal aerobic power showed higher CVIs than those in less aerobically fit subjects (VO2max < 50% subgroup, p = 0.009; VO2max < 75% subgroup, p = 0.034). Both transient results differed for asymptomatic and cardiac subjects (CVI, 1.32 +/- 0.02 vs 1.42 +/- 0.02, respectively [p = 0.001]; HRR, 33 +/- 1 beats/min (bpm) vs 37 +/- 1 bpm, respectively [p = 0.009]). CONCLUSIONS: The initial and final HR transients were modestly related, suggesting a potentially complementary clinical role for both measurements in the assessment of autonomic function in patients with coronary artery disease. Although both HR transients tended to behave similarly under the influence of several variables, the initial HR transient, measured during 4sET, was more likely to discriminate distinct subgroups compared with the final HR transient.     

Abnormal chronotropic reserve and heart rate recovery in patients with SLE: a case-control study

Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5?±?1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5?±?1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (ΔHRR) was defined as the difference between HR at peak exercise and at both first (ΔHRR1) and second (ΔHRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6?±?0.9 vs. 36.7?±?1.1?ml/kg/min, p?=?0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8?±?2.4 vs. 98.2?±?2.6%, p?=?0.001), ΔHRR1 (22.1?±?2.5 vs. 32.4?±?2.2%, p?=?0.004) and ΔHRR2 (39.1?±?2.9 vs. 50.8?±?2.5%, p?=?0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed ΔHRR.     

Predictors of survival in patients with end-stage renal disease evaluated for kidney transplantation

Cardiovascular disease is the major cause of mortality in patients with end-stage renal disease (ESRD). This study examined the all-cause mortality in 3,698 patients with ESRD evaluated for kidney transplantation at our institution from 2001 to 2004. Mean age for the cohort was 48+/-12 years, and 42% were women. Stress myocardial perfusion imaging was done in 2,207 patients (60%) and coronary angiography in 260 patients (7%). There were 622 deaths (17%) during a mean follow-up period of 30+/-15 months. The presence and severity of coronary disease on angiography was not predictive of survival. Coronary revascularization did not impact survival (p=0.6) except in patients with 3-vessel disease (p=0.05). The best predictor of death was left ventricular ejection fraction, measured by gated myocardial perfusion imaging, with 2.7% mortality increase for each 1% ejection fraction decrease. In conclusion, left ventricular ejection fraction is a strong predictor of survival in patients with ESRD awaiting renal transplantation. Strategies to improve cardiac function or earlier renal transplantation deserve further studies.