Early recovery of oxygen kinetics after submaximal exercise test predicts functional capacity in patients with chronic heart failure.

BACKGROUND: Oxygen (O2) uptake at peak exercise (VO2 peak) is an objective measurement of functional capacity in patients with chronic heart failure (CHF). The significance of recovery O2 kinetics parameters in predicting exercise capacity, and the parameters of submaximal exercise testing have not been thoroughly examined. METHODS AND RESULTS: Thirty-six patients (mean age = 48+/-14 years) with CHF and New York Heart Association functional class I, II, or III, and eight healthy volunteers (mean age = 39+/-13 years) were studied with maximal and submaximal cardiopulmonary exercise testing (CPET). The first degree slope of O2 uptake decay during early recovery from maximal (VO2/t-slope), and submaximal exercise (VO2/t-slope)(sub), were calculated, along with VO2 half-time (T(1/2)VO2). Patients with CHF had a longer recovery of O2 uptake after exercise than healthy volunteers, expressed by a lower VO2/t-slope (0.616+/-0.317 vs. 0.956+/-0.347 l min(-1) min(-1), P=0.029) and greater T(1/2)VO2 (1.28+/-0.30 vs. 1.05+/-0.15 min, P = 0.005). VO2/t-slope correlated with the VO2 peak (r = 0.84, P<0.001), anaerobic threshold (r = 0.79, P<0.001), and T(1/2)VO2, a previously established estimate of recovery O2 kinetics (r = -0.59, P<0.001). (VO2/t-slope)(sub) was highly correlated with VO2/t-slope after maximal exercise (r=0.87, P<0.001), with the VO2 peak (r=0.87, P<0.001) and with T(1/2)VO2 after maximal exercise (r=-0.62, P<0.001). VO2/t-slope after maximal and submaximal exercise was reduced in patients with severe exercise intolerance (F=9.3, P<0.001 and F=12.8, P<0.001, respectively). CONCLUSIONS: Early recovery O2 kinetics parameters after maximal and submaximal exercise correlate closely with established indices of exercise capacity in patients with CHF and in healthy volunteers. These findings support the use of early recovery O2 kinetics after submaximal exercise testing as an index of functional capacity in patients with CHF.     

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.     

Prolonged recovery of cardiac output after maximal exercise in patients with chronic heart failure

OBJECTIVES: The aim of this study was to characterize the kinetics of cardiac output during recovery from maximal exercise in patients with chronic heart failure (CHF). BACKGROUND: Recent studies have shown that oxygen uptake kinetics during recovery from exercise are delayed in patients with CHF. However, the kinetics of cardiac output during recovery from maximal exercise in CHF has not been examined. METHODS: Thirty patients with CHF performed maximal upright ergometer exercise with respiratory gas analysis. Kinetics of oxygen uptake (VO2) and carbon dioxide output (VCO2) during recovery were characterized by T1/2, the time to reach 50% of the peak values. Cardiac output was measured at 1-min intervals during exercise and recovery. Kinetics of cardiac output during recovery were characterized by the ratios of cardiac output during the first 4 min of recovery to cardiac output at peak exercise. Overshoot of cardiac output was defined as a further increase in cardiac output at 1 min of recovery above the cardiac output at peak exercise. RESULTS: Both T1/2 VO2 and T1/2 VCO2 increased as CHF worsened. The ratios of cardiac output during recovery to cardiac output at peak exercise were significantly correlated with T1/2 VO2 (r = 0.47 to 0.62, p < 0.05) and T1/2 VCO2 (r = 0.40 to 0.70, p < 0.05). There was a negative correlation between cardiac index at peak exercise and both T1/2 VO2 (r = -0.65, p < 0.001) and T1/2 VCO2 (r = -0.60, p < 0.001). Overshoot of cardiac output was recognized in 11 of 30 patients. Cardiac index at peak exercise was significantly lower in patients with overshoot (4.5 +/- 0.9 L/min/m2) than in those without overshoot (6.1 +/- 2.1 L/min/m2, p < 0.05). However, because of a continued increase in cardiac output at 1 min of recovery in patients with overshoot, there were no differences in cardiac index after the first minute of recovery. Heart rate at peak exercise and recovery of heart rate did not differ between these groups. Overshoot of cardiac output was caused by a rebound increase in stroke volume which was due to a reduction in systemic vascular resistance. CONCLUSIONS: Prolonged kinetics of VO2 or VCO2 during recovery from maximal exercise represent impairment of circulatory response to exercise and delayed recovery of cardiac output after exercise. Overshoot of cardiac output at 1 min of recovery was characteristic of severe CHF with poor cardiac output response to exercise.     

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.     

Assessment of the functional status of heart failure in non ischemic dilated cardiomyopathy: an echo-dobutamine study.

BACKGROUND: The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO2 max). Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of chronic HF in patients with dilated cardiomyopathy, by investigating the changes in echo-variables, as assessed by echo-dobutamine, in relation with VO2 max. METHODS AND RESULTS: A low infusion rate echo-dobutamine test (10 micrograms/kg/min) was performed in 30 patients with dilated cardiomyopathy and 1 h later VO2 max was measured. VO2 max (ranging from 7.6 to 23 ml/kg/min, mean 14.06 +/- 0.64 ml/kg/min) was correlated with the changes (values obtained after inotropic stimulation minus those obtained at baseline) in left ventricular end-systolic diameter (r:0.80, p:0.001), in left ventricular end-systolic posterior wall thickness (r:0.73, p:0.001) and in left ventricular heart-rate corrected mean velocity of circumferential fiber shortening (Vcfc)/end-systolic meridional wall stress ratio (r:0.64, p:0.0001). A negative correlation was found between VO2 max and the changes in end-systolic meridional wall stress (r: -0.76, p:0.001). After dobutamine infusion Vcfc/systolic meridional wall stress ratio increased in patients with VO2 max > 14 ml/kg/min but decreased in patients with VO2 max < 14 ml/kg/min (0.0001 +/- 0.0001 vs -0.0002 +/- 0.0003 circ x cm2/g x s, p:0.0001). End-systolic meridional wall stress was decreased in patients with VO2 max > 14 ml/kg/min but increased in patients with VO2 max < 14 ml/kg/min (-126.97 +/- 34.24 vs 205.77 +/- 56.71 g/cm2, p:0.0001). CONCLUSION: The changes in echo-variables assessed by echo-dobutamine are well correlated with VO2 max and seem to be accurate for evaluating the functional status of chronic HF in patients with dilated cardiomyopathy.     

重度慢性阻塞性肺疾病患者运动过程中摄氧动力学变化特点研究

目的 研究摄氧量动力学在重度慢性阻塞性肺疾病(COPD)患者心肺运动试验(cardiopulmonary exercise test,CPET)检测中的变化特点,探讨COPD严重程度对摄氧动力学的影响.方法对20例Ⅲ级COPD、17例Ⅳ级COPD患者及18名正常健康者进行常规肺功能检测(pulmonary functi...     

Dependence of enhanced maximal exercise performance on increased peak skeletal muscle perfusion during long-term captopril therapy in heart failure

Maximal oxygen uptake (VO2), skeletal muscle blood flow by xenon-133 washout technique and femoral vein arteriovenous oxygen difference and lactate were measured at rest and during maximal bicycle exercise in eight patients with severe congestive heart failure before and after 8 weeks of therapy with captopril. During therapy, skeletal muscle blood flow at rest increased significantly from 1.5 +/- 0.6 to 2.6 +/- 1.0 ml/100 g per min (p less than 0.05), with a concomitant decrease in the femoral arteriovenous oxygen difference from 10.0 +/- 1.7 to 8.3 +/- 1.9 ml/100 ml (p less than 0.05). Maximal VO2 increased significantly from 13.4 +/- 3.0 to 15.5 +/- 4.1 ml/kg per min (p less than 0.05). In four patients, the increase in maximal VO2 averaged 3.7 ml/kg per min (range 2.7 to 4.9), whereas in the remaining four patients, it was less than 1 ml/kg per min. Overall, peak skeletal muscle blood flow attained during exercise did not change significantly during long-term therapy with captopril (19.6 +/- 6.2 versus 27.6 +/- 14.3 ml/100 g per min, p = NS). However, the four patients with a significant increase in maximal VO2 experienced substantial increases in peak skeletal muscle blood flow and the latter changes were linearly correlated with changes in maximal VO2 (r = 0.95, p less than 0.001). Femoral arteriovenous oxygen difference at peak exercise was unchanged (12.6 +/- 2.6 versus 12.6 +/- 2.4 ml/100 ml). Thus, improvement in maximal VO2 produced by long-term therapy with captopril is associated with an increased peripheral vasodilatory response to exercise, and this improvement only occurs when the peak blood flow is augmented.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resting lung function and hemodynamic parameters as predictors of exercise capacity in patients with chronic heart failure

STUDY OBJECTIVES: The aim of this study was to examine the role of resting pulmonary function and hemodynamic parameters as predictors of exercise capacity in patients with chronic heart failure. MEASUREMENTS AND RESULTS: Fifty-one patients with chronic heart failure underwent resting pulmonary function testing, including inspiratory capacity (IC) and symptom-limited, treadmill cardiopulmonary exercise testing (CPET). Right-heart catheterization and radionuclide ventriculography were performed within 2 days of CPET. Mean (+/- SD) left ventricular ejection fraction was 31 +/- 12% and cardiac index was 2.34 +/- 0.77 L/min/m(2). Percentage of predicted FEV(1) was 92 +/- 14%, percentage of predicted FVC was 94 +/- 15%, FEV(1)/FVC was 81 +/- 4%, and percentage of predicted IC was 84 +/- 18%. Mean peak oxygen uptake (peak O(2)) was 17.9 +/- 5.4 mL/kg/min. Analysis of variance among the three functional Weber classes showed statistically significant differences for pulmonary capillary wedge pressure (PCWP) and IC. Specifically, the more severe the exercise intolerance, the lower was IC and the higher was PCWP. In a multivariate stepwise regression analysis, using peak O(2) (liters per minute) as the dependent variable and the pulmonary function test measurements as independent variables, the only significant predictor selected was IC (r = 0.71, p < 0.0001). In a final stepwise regression analysis including all the independent variables of the resting pulmonary function tests and hemodynamic measurements, the two predictors selected were IC and PCWP (r(2) = 0.58). CONCLUSIONS: In patients with chronic heart failure, IC is inversely related to PCWP and is a strong independent predictor of functional capacity.     

摄氧量平均反应时间在重度慢性阻塞性肺疾病患者心肺功能评估中的应用研究

目的 探讨重度慢性阻塞性肺疾病(COPD)患者在心肺运动试验(cardiopulmonary exercise test,CPET)检测零负荷热身期中的摄氧量动力学改变特点,研究零负荷热身期间摄氧量平均反应时间(mean response time,MRT)与COPD患者心肺功能及常规肺功能的相关性,探讨MRT值评价重...     

Prediction of PaO2 during treadmill walking in patients with COPD

We studied the possibility of predicting PaO2 during exercise of a given oxygen uptake (VO2) from resting pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD). The three-minute incremental treadmill exercise was performed with serial measurements of PaO2 via intra-arterial catheter in 46 patients (mean FEV1 = 1.09 +/- 0.49L, mean FEV1/FVC = 44 +/- 15 percent). In most of the patients, the changes of PaO2 were quite linear in relation to the oxygen uptake, so a slope (PaO2/VO2) could be obtained from the regression equation in each patient. The mean value of the slope (SL) was -23.0 +/- 16.6 mm Hg/L VO2/min. Correlation between SL and all parameters of resting PFTs were computed. Because of the high correlation coefficient between SL and %DCO (SL = -59.3 + 0.501 X %DCO, r = 0.851, p less than 0.001), it was possible to predict PaO2 at a given VO2 using the following equation: PaO2 predicted = PaO2 rest + SL X (VO2 -0.25), where SL was derived from measured %DCO and resting VO2 was assumed 0.25 L/min. There was a high correlation between the predicted PaO2 at VO2 of 1.0 L/min and the estimated PaO2 obtained from individual PaO2 regression with an r value = 0.898 and SEE = +/- 5.8 mm Hg. A prospective study in 12 patients with COPD was then carried out. There was a high correlation (r = 0.857) between the predicted PaO2 obtained from the present equation and the estimated PaO2 at VO2 = 1.0 L/min. It was concluded that PaO2 during treadmill walking with a given oxygen uptake is predictable from a resting PaO2 and a diffusing capacity. This predicted value may be useful in the management of patients with COPD.     

Response to one-legged cycling in patients with COPD

BACKGROUND: In patients with COPD, exercise intensity is often limited by the ventilatory system. We hypothesized that by exercising with a smaller muscle mass, ventilatory-limited patients would perform more high-intensity, muscle-specific work. The study objectives were as follows: (1) to determine the limitations of exercising with a smaller muscle mass, compared with conventional two-legged exercise; and (2) to determine the endurance time, using the same muscle-specific intensity, during one-legged vs two-legged exercise. METHODS: Nine patients (mean +/- SD FEV1, 36 +/- 13% of predicted) completed incremental exercise, and nine other patients (mean FEV1, 42 +/- 16% of predicted) completed constant-power exercise. Nine healthy subjects (FEV1, 104 +/- 14% of predicted) completed both tests. All subjects completed tests using two-legged and one-legged pedaling. RESULTS: Peak oxygen uptake (VO2peak) was similar during one-legged and two-legged incremental exercise among patients (difference, 0.03 L/min; 95% confidence interval [CI], -0.10 to 0.16 L/min; p = 0.60), as were ventilation and dyspnea scores. VO2peak was lower during one-legged vs two-legged exercise (-0.57 mL/min; 95% CI, -0.81 to -0.32 mL/min; p < 0.001) among healthy subjects with substantial ventilatory and heart rate reserve. Patients endured one-legged pedaling at a constant power longer than two-legged pedaling (16.97 min; 95% CI, 9.98 to 23.96 min; p < 0.001), resulting in greater work (12.48 kilojoules [kJ]; 95% CI, 2.58 to 22.39 kJ; p = 0.02). Healthy subjects completed similar work (-4.02 kJ; 95% CI, -18.59 to 10.55 kJ; p = 0.54) with one-legged vs two-legged pedaling. CONCLUSION: These observations demonstrate the effectiveness of using one-legged exercise at the same muscle-specific intensity in extending the duration of exercise among patients with COPD. This has important implications for training approaches designed to enhance exercise function among ventilatory-limited patients.     

Exercise oscillatory ventilation may predict sudden cardiac death in heart failure patients.

OBJECTIVES: The purpose of this study was to test the ability of cardiopulmonary exercise testing (CPET)-derived variables as sudden cardiac death (SCD) predictors. BACKGROUND: The CPET variables, such as peak oxygen uptake (VO2), ventilatory requirement to carbon dioxide (CO2) production (VE/VCO2) slope, and exercise oscillatory breathing (EOB), are strong predictors of overall mortality in chronic heart failure (CHF) patients. Even though up to 50% of CHF patients die from SCD, it is unknown whether any of these variables predicts SCD. METHODS: One hundred fifty-six CHF patients (mean age: 60.9 +/- 9.4 years; mean ejection fraction: 34.9 +/- 10.6%) underwent CPET. Subjects were tracked for sudden versus pump-failure cardiac mortality over 27.8 +/- 25.2 months. RESULTS: Seventeen patients died from SCD, and 17 died from cardiac pump failure. Survivors showed significantly higher peak VO2 (16.8 +/- 4.5 ml x kg(-1) x min(-1)) and lower VE/VCO2 slope (32.8 +/- 6.4) and prevalence of EOB (20.3%), compared with subjects who experienced arrhythmic (13.5 +/- 3.2 ml x kg(-1) x min(-1); 41.5 +/- 11.4; 100%) or nonarrhythmic (14.1 +/- 4.7 ml x kg(-1) x min(-1); 38.1 +/- 7.3; 47.1%) deaths (p < 0.05). At Cox regression analysis, all variables were significant univariate predictors of both sudden and pump failure death (p < 0.01). Multivariate analysis, including left ventricular (LV) ejection fraction, LV end systolic volume, and LV mass selected EOB, was the strongest predictor of both overall mortality (chi-square: 38.7, p < 0.001) and SCD (chi-square: 44.7, p < 0.001), whereas VE/VCO2 slope was the strongest ventilatory predictor of pump failure death (chi-square: 11.8, p = 0.001). CONCLUSIONS: Exercise oscillatory breathing is an independent predictor of SCD in patients with CHF and might help as an additional marker for prioritization of antiarrhythmic strategies.     

Prognostic value of resting end-tidal carbon dioxide in patients with heart failure

BACKGROUND: Cardiopulmonary exercise testing (CPET) variables provide valuable prognostic information in the heart failure (HF) population. The purpose of the present study is to assess the ability of resting end-tidal carbon dioxide partial pressure (PETCO2) to predict cardiac-related events in patients with HF. METHODS: 121 subjects diagnosed with compensated HF underwent CPET on an outpatient basis. Mean age and ejection fraction were 49.3 years (+/-14.7) and 28.4% (+/-13.4), respectively. Resting P(ET)CO2 was determined immediately prior to the exercise test in the seated position. Peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production (VE/VCO2) slope were also acquired during CPET. RESULTS: There were 41 cardiac-related hospitalizations and 9 cardiac-related deaths in the year following CPET. Mean resting P(ET)CO2, peak VO2 and VE/VCO2 slope were 34.1 mmHg (+/-4.6), 14.5 ml*kg(-1)*min(-1) (+/-5.1) and 35.9 (+/-8.7) respectively. Univariate Cox regression analysis revealed that resting P(ET)CO2 (Chi-square=28.4, p<0.001), peak VO2 (Chi-square=21.6, p<0.001) and VE/VCO2 slope (Chi-square=54.9, p<0.001) were all significant predictors of cardiac related events. Multivariate Cox regression analysis revealed resting P(ET)CO2 added to the prognostic value of VE/VCO2 slope in predicting cardiac related events (residual Chi-square=4.4, p=0.04). Peak VO2 did not add additional value and was removed (residual Chi-square=3.2, p=0.08). CONCLUSIONS: These results indicate a resting ventilatory expired gas variable possesses prognostic value independently and in combination with an established prognostic marker from the CPET. Resting P(ET)CO2 may therefore be a valuable objective measure to obtain during both non-exercise and exercise evaluations in patients with HF.     

Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity

BACKGROUND: Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. METHODS: Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). RESULTS: The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4+/-4.2 versus 17.8+/-4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1+/-6.8 versus 34+/-5.3, p<0.0001). In the univariate model, age (r=-0.36, p<0.0001), female sex (r=-0.21, p=0.001), ischemic CHF etiology (r=-0.26, p<0.0001) and NYHA class (r=-0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology (beta=-0.23, p=0.001) was a predictor of peak VO2 (R(2)=0.49) independently of age (beta=-0.23, p=0.001), female sex (beta=-0.25, p=0.0006) and NYHA class (beta=-0.31, p<0.0001). Similarly, ischemic etiology (beta=0.29, p=0.001) predicted the VE/VCO2 slope (R(2)=0.38) independently of E/A ratio (beta=0.27, p=0.01) and resting heart rate (beta=0.22, p=0.01). CONCLUSIONS: Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.     

Relations among heart failure severity,left ventricular loading conditions,and repolarization length in advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In patients with heart failure (HF), low peak oxygen consumption (VO(2)) and prolonged QT interval or enhanced QT variability are associated with poor prognosis. Whether HF severity or left ventricular (LV) loading conditions can influence repolarization length is unknown. Survival, QTc interval, peak VO(2), clinical, laboratory, echocardiographic, and invasive hemodynamic data were analyzed in 154 transplant candidates; mortality was examined after a mean follow-up of 4.3 +/- 1.8 years. The relation between the QTc interval and other variables was examined using multivariate analysis and multiple correlation coefficients. Patients were stratified by peak VO(2) to study its relation with peak VO(2), mortality, loading conditions, and QTc intervals. Mean ejection fraction was 10 +/- 9%; mean cardiac index was 2.06 +/- 0.7 L/min/m(2). Seventy-one patients (47%) were dead at the end of study. Mortality and nonfatal ventricular arrythmias were higher (p <0.01) in patients with lower peak VO(2) and longer QTc intervals (p <0.001). An inverse correlation was found between QTc interval length and peak VO(2) (r = -0.790, p <0.0001). No correlation was found between QTc interval and LV loading conditions or the other analyzed variables. Thus, repolarization length measured by the QTc interval is inversely correlated with HF severity measured by peak VO(2) and is independent of LV loading conditions in patients with severe HF.     

Long-term combined therapy with losartan and an angiotensin-converting enzyme inhibitor improves functional capacity in patients with left ventricular dysfunction

OBJECTIVE: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure (HF) is well documented. However, ACE inhibitors may provide incomplete blockade of the renin-angiotensin-aldosterone system due to the alternative pathways for the production of angiotensin II (Ang II). The aim of this study was to evaluate the efficacy of combined therapy of an ACE inhibitor and the Ang II receptor blocker losartan in patients with HF by using cardiopulmonary exercise testing (CPET) on a treadmill. METHODS AND RESULTS: Seventeen patients (ejection fraction < or = 40%) were included in the study group. At the start of the study, all participants were on chronic ACE inhibitors therapy. Fifty mg losartan was added to the treatment and CPET was performed before and 6-8 months after starting losartan therapy. Sixteen patients with HF were included in the control group. CPET was performed once at the beginning and repeated 6-8 months later without any change in the treatment protocol. The change in CPET values (walk-time (WT), peakVO2, anaerobic threshold (AT), minute ventilation (VE), VE/VO2, peak heart rate (HR),VO2/HR) was investigated. In the losartan-treated group a significant increase was noted in WT (393 +/- 157 vs. 507 +/- 155 sec, p < 0.01); peak VO2 (1205 +/- 240 vs. 1330 +/- 253 ml/min, p < 0.05); and AT (794 +/- 131 vs. 895 +/- 177 ml/min, p < 0.05). In the control group exercise parameters did not change significantly. The change from baseline to follow-up between the two groups is statistically significant for WT and peak VO2 (114 +/- 94 vs. -58 +/- 134 sec, p < 0.0 1 and 125 +/-183 vs. -116 +/- 221 ml/min, p <0.01). CONCLUSIONS: Addition of losartan to the ACE inhibitor therapy in patients with HF improves functional capacity in the long run.     

Optimal protocol selection for cardiopulmonary exercise testing in severe COPD

BACKGROUND: The current recommendations of 8 to 12 min for the optimal targeted duration of symptom-limited maximal cardiopulmonary exercise testing (CPET) to attain maximal oxygen consumption are based on results from healthy individuals and may not be applicable to patients with severe COPD. We aimed to determine the optimal duration for a CPET to attain the peak oxygen consumption (VO2peak) in a group of patients with severe COPD using different carefully conducted workload protocols. METHODS: We studied 11 subjects with severe COPD (mean FEV1, 32% predicted; 95% confidence interval [CI], 27 to 38% predicted). They completed four incremental, symptom-limited exercise tests on a cycle ergometer using four protocols (4, 8, and 16 W/min continuous ramp protocols, and 8 W/min step protocol) using a randomized double-blind design. RESULTS: The mean duration of these 44 tests was 6.3 min (95% CI, 5.0 to 9.0 min). The duration of the exercise tests differed significantly for the protocols used, as follows: 16-W ramp protocol, 4.0 min (95% CI, 3.0 to 5.1 min); 8-W ramp protocol, 6.6 min (95% CI, 5.0 to 9.0 min); 8-W step protocol, 6.0 min (95% CI, 4.0 to 8.0 min); and 4-W ramp protocol, 8.7 min (95% CI, 4.4 to 13.0 min; p<0.001). The maximal workload significantly increased as the ramp slope increased from 4 to 8 to 16 W/min (maximal workload, 35.6 vs 50.7 vs 64.3 W, respectively; p<0.001). Maximal minute ventilation, heart rate, Borg ratings, and VO2 peak, were not different among the four protocols. No differences were found between the ramp and step protocols. CONCLUSIONS: In patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease stages III-IV), a targeted duration of 5 to 9 min for a CPET appears to be more appropriate than the 8 to 12 min proposed in the current guidelines. Maximal workload, in contrast to VO2peak, is highly dependent on the ramp incrementation rate.     

The effect of percutaneous transluminal coronary angioplasty on anaerobic threshold in patients with angina pectoris.

The anaerobic threshold (AT) is regarded an objective parameter for evaluating exercise tolerance, but its relationship to the improvement of myocardial ischemia remains uncertain. To investigate this relationship, submaximal treadmill exercise tests were performed for 15 consecutive patients with angina pectoris who had undergone successful percutaneous transluminal coronary angioplasty (PTCA). Before and after PTCA, the AT was determined using cardiorespiratory monitoring, while the patients were receiving their usual vasodilator medications. 1) Before PTCA, the minute oxygen uptake (VO2) at the AT correlated well with the peak VO2 (r = 0.92, p < 0.002). The VO2 at the AT, however, showed less correlation (r = 0.71, p < 0.002) with the VO2 at ST segment depression, while the latter parameter correlated closely with the peak VO2 (r = 0.91, p < 0.002). 2) After PTCA, exercise time, peak VO2, and the double product at peak exercise increased significantly (from 640.1 +/- 212.2 to 772.9 +/- 230.0 sec, p < 0.001, from 19.1 +/- 5.2 to 22.4 +/- 4.9 ml/min/kg, p < 0.05, and from 19.7 +/- 5.0 x 10(3) to 23.7 +/- 4.5 x 10(3), p < 0.001, respectively). However, the VO2 at the AT did not increase significantly (from 15.8 +/- 4.1 to 16.6 +/- 3.5 ml/min/kg, p = NS). The heart rate, systolic blood pressure, and double product at the AT did not change significantly. In conclusion, in patients with angina pectoris, the AT is apparently related to the onset of myocardial ischemia. However, the AT does not necessarily reflect acute improvement of myocardial ischemia immediately after PTCA.     

Usefulness of low-dose dobutamine echocardiography in idiopathic dilated cardiomyopathy.

INTRODUCTION: Low-dose dobutamine stress echocardiography is a common and useful technique to assess myocardial viability in patients with ischemic cardiomyopathy. OBJECTIVE: To evaluate the use of low-dose dobutamine stress echocardiography in determining the functional status of patients with idiopathic dilated cardiomyopathy (IDCM). METHODS: Prospective study of 28 patients with IDCM by transthoracic echocardiography (2D), low-dose dobutamine stress echocardiography, cardiopulmonary exercise testing (CPET) and measurement of pro-BNP. RESULTS: The mean age of the population was 50.3 +/- 11.5 years, 9 female and 19 male. Mean ejection fraction was 32.1 +/- 9.8%. All were in sinus rhythm. The following parameters were analyzed in 2D echocardiography and after dobutamine: dimensions of left atrium (LA) and of left ventricle in diastole and systole, shortening fraction (%), left ventricular end-diastolic (EDV) and end-systolic volumes (ESV), ejection fraction (EF), and mitral inflow (E, A, E/A ratio and deceleration time). In CPET, we considered the following parameters: peak VO2 and % maximal peak VO2 attained. We compared echo results with CPET. There was a correlation between age and peak VO2 (r = -0.38 with p = 0.049). In 2D echo, there was a correlation between baseline EF and LA dimensions and peak VO2 (r = 0.45 / p = 0.004 and r = -0.49 / p = 0.014, respectively). After dobutamine echo, there was a correlation between some echo parameters and peak VO2: EF - r = 0.59 / p = 0.001, LA dimensions - r = 0.56 / p = 0.007, and ESV - r = -0.45 / p = 0.026. Percentage maximal peak VO2 attained correlated with LA dimensions measured in 2D echo and after dobutamine (r = -0.398 / p = 0.036 and r = -0.674 / p = 0.02 respectively) and EF after dobutamine (r = -0.389 / p = 0.04). The value of pro-BNP correlated with LA dimensions and baseline EF (r = 0.44 / p = 0.02 and r = -0.57 / p = 0.002, respectively), and the correlation was maintained after inotropic stimulation with dobutamine (r = 0.57 / p = 0.001 and r = -0.55 / p = 0.0039). CONCLUSION: Low-dose dobutamine stress echocardiography showed stronger correlations with cardiopulmonary exercise testing than the parameters evaluated by conventional echocardiography and could be used to determine the functional status of patients with dilated cardiomyopathy; patients with greater ejection fraction after inotropic stimulation had better cardiopulmonary tests.     

Effects of exercise rehabilitation program on heart rate recovery in patients with chronic heart failure.

BACKGROUND: Heart rate recovery (HRR1) immediately after exercise reflects parasympathetic activity, which is markedly attenuated in chronic heart failure (CHF) patients. The aim of our study was to examine both continuous and interval exercise training effects on HRR1 in these patients. DESIGN: The population study consisted of 29 stable CHF patients that participated at a rehabilitation program of 36 sessions, three times per week. Of the 29 patients, 24 completed the program. Patients were randomly assigned to interval {n=10 [100% peak work rate (WRp) for 30 s, alternating with rest for 30 s]} and to continuous training [n=14 (50%WRp)]. METHODS: All patients performed a symptom-limited cardiopulmonary exercise test on a cycle ergometer before and after the completion of the program. Measurements included peak oxygen uptake (VO2p), anaerobic threshold (AT), WRp, first degree slope of VO2 during the first minute of recovery (VO2/t-slope), chronotropic response [% chronotropic reserve (CR)=(peak HR - resting HR)x100/(220 - age - resting HR)], HRR1 (HR difference from peak exercise to one minute after). RESULTS: After the completion of the rehabilitation program there was a significant increase of WRp, VO2p, AT and VO2/t-slope (by 30%, P=0.01; 6%, P=0.01; 10%, P=0.02; and 27%, P=0.03 respectively for continuous training and by 21%, P<0.05; 8%, P=0.01; 6%, P=NS; and 48%, P=0.02 respectively for interval training). However, only patients exercised under the continuous training regime had a significant increase in HRR1 (15.0+/-9.0 to 24.0+/-12 bpm; P=0.02) and CR (57+/-19 to 72+/-21%, P=0.02), in contrast with those assigned to interval training (HRR1: 21+/-11 to 21+/-8 bpm; P=NS and CR: 57+/-18 to 59+/-21%, P=NS). CONCLUSIONS: Both continuous and interval exercise training program improves exercise capacity in CHF patients. However, continuous rather than interval exercise training improves early HRR1, a marker of parasympathetic activity, suggesting a greater contribution to the autonomic nervous system.