The ability of a submaximal exercise test to predict maximal exercise capacity in patients with heart failure

We investigated the ability of a submaximal exercise test topredict the maximal aerobic potential and hence exercise capacityof patients with chronic heart failure. Heart rate, oxygen consumptionand carbon dioxide production were measured continuously duringtreadmill exercise in 29 patients with chronic heart failure(NYHA Class II-III). The anaerobic threshold was determinedas the oxygen consumption at which carbon dioxide productionincreased non-linearly relative to oxygen consumption.Maximaloxygen consumption could not be predicted from the heart rateresponse to submaximal exercise.Oxygen consumption at the anaerobicthreshold (28 patients) and at a respiratory quotient of 1 (23patients) did predict maximal oxygen consumption (r = 0.93,r = 0.88, respectively). Measurement of oxygen consumption duringsubmaximal exercise can be used to assess maximal exercise capacityin patients with heart failure.     

Biomechanical efficiency is decreased in heart failure during low-level steady state and maximal ramp exercise

BACKGROUND: Previous studies of biomechanical efficiency (external work/energy input--Watt/O(2) consumed) in heart failure (HF) using cardiopulmonary exercise testing (CPET) and magnetic resonance spectroscopy (MRS) have had discordant results with increased efficiency by CPET and decreased efficiency by MRS. AIMS: Compare biomechanical efficiency of HF subjects and normal controls during steady state (SS=35 W for 6 min) and ramp cycle ergometer exercise. The hypothesis was that HF subjects would have impaired biomechanical efficiency that correlated with HF symptoms. METHODS: Biomechanical efficiency used the actual Vo(2) during exercise and recovery. Gross (Vo(2) above zero), Net (Vo(2) above the resting Vo(2)) and Work (Vo(2) above the unloaded pedaling Vo(2)) efficiencies were calculated. RESULTS: HF subjects had an 18% higher Vo(2) during SS exercise (P=0.029). Biomechanical efficiency was reduced during SS exercise (gross -15%, P=0.019, net -15%, P=0.062, and work -35%, P=0.002). Gross Efficiency during SS exercise had the strongest correlation with HF symptoms (r=0.55). During ramp exercise gross (-26%), net (-10%) and work (-8%) biomechanical efficiency were all reduced (all P<0.05). The slope of the Vo(2)/Watt relationship during ramp exercise had the best correlation with HF symptoms (r=0.46). CONCLUSIONS: HF subjects have an increased O(2) cost/Watt during SS and ramp exercise that correlates with HF symptoms of fatigue and breathlessness. Methods to improve biomechanical efficiency in HF subjects by exercise training or medications may improve the symptoms and the impaired exercise capacity associated with HF.     

Prognostic value of brain natriuretic peptide and enhanced ventilatory response to exercise in patients with chronic heart failure

Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) <40%, we assessed the impact of BNP assay, Doppler echocardiography and CPx on survival. Median BNP plasma levels were 207 [90–520] pg/mL. Mean LVEF was 33 ± 7%. Left bundle branch block (LBBB) was present in 52 patients (33%) and a restrictive filling pattern in 35 (22%). The slope of the relation between minute ventilation and carbon dioxide production (VE/VCO₂ slope) averaged 35 ± 8; an enhanced ventilatory response (EVR) to exercise (VE/VCO₂ slope >35) was found in 67 patients (43%). During 759 ± 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO₂ slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.     

Work-rate affects cardiopulmonary exercise test results in heart failure

AIMS: Cardiopulmonary exercise test (CPET) is used to evaluate patients with chronic heart failure (HF) usually by means of a personalized ramp exercise protocol. Our aim was to evaluate if exercise duration or ramp rate influences the results. METHODS AND RESULTS: Ninety HF patients were studied (peak V (O(2)): >20 ml/min/kg, n=28, 15-20 ml/min/kg, n=39 and <15 ml/min/kg, n=23). Each patient did four CPET studies. The initial study was used to separate the subjects into three groups, according to their exercise capacity. In the remaining studies, work-rate was increased at three different rates designed to have the subjects reach peak exercise in 5, 10 and 15 min from the start of the ramp increase in work-rate, respectively. The order was randomized. The work-rate applied for the total population averaged 22.7+/-8.0, 11.6+/-3.7, 7.5+/-2.9 W/min with effective loaded exercise duration of 5 min and 16 s+/-29 s, 9 min and 43 s+/-49 s and 14 min and 32 s+/-1 min and 12 s for the 5-, 10- and 15-min tests, respectively. Peak V (O(2)) averaged 16.9+/-4.3*, 18.0+/-4.4 and 18.0+/-5.4 ml/min/kg for the 5-, 10- and 15-min tests, (*=p<0.001 vs. 10 min). The shortest test had the lowest peak heart rate and ventilation and highest peak work-rate. Peak V (O(2)) and heart rate were lowest in 5-min tests regardless of HF severity. The DeltaV (O(2))/Deltawork-rate was lowest in 5-min tests and highest in 15-min tests. At all ramp rates, DeltaV (O(2))/Deltawork-rate was lower for the subjects with the lower peak V (O(2)). The V (e)/V (CO(2)) slope and V (O(2)) at anaerobic threshold were not affected by the protocol for any grade of HF. CONCLUSIONS: In chronic HF, exercise protocol has a small effect on peak V (O(2)) and DeltaV (O(2))/Deltawork but does not affect V (O(2)) at anaerobic threshold and V (e)/V (CO(2)) slope.     

Neuro-hormonal activation predicts ventilatory response to exercise and functional capacity in patients with heart failure

BACKGROUND: Heart failure (HF) is characterised by reduced tolerance to effort, associated with progressive fatigue and dyspnoea. Neuro-hormonal activation is a hallmark of HF and influences its clinical evolution. AIM: To evaluate the relationship between neuro-hormonal activation, exercise capacity and ventilatory efficiency. METHODS AND RESULTS: 154 HF patients (127 males, 62 +/- 1 years) underwent cardiopulmonary exercise testing and resting blood sampling for assay of plasma brain natriuretic peptide (BNP), NT-proBNP, norepinephrine, epinephrine, aldosterone and plasma renin activity (PRA). BNP and NT-proBNP levels correlated with peak oxygen consumption (VO2) (both R = -0.53, p < 0.001), VE/VCO2 slope (R = 0.56; p < 0.001 and R = 0.58; p < 0.001, respectively) and maximum workload (R = -0.49; p < 0.001 and R = -0.47; p < 0.001, respectively). Norepinephrine correlated slightly less with peak VO2 (R = -0.38, p < 0.001), VE/VCO2 (R = 0.45; p < 0.001) and maximum workload (R = -0.35; p < 0.001). There was a significant inverse correlation between left ventricular ejection fraction and BNP (R = -0.48, p < 0.001), NT-proBNP (R = -0.42; p < 0.001) and norepinephrine (R = -0.43; p < 0.001). Weaker correlations were found for PRA, exercise parameters and ejection fraction. ROC curves showed that BNP was able to identify patients with peak VO2 < 14 ml/min/kg (cut-off 98 pg/ml, AUC 0.775) and a VE/VCO2 > 35 (cut-off 183 pg/ml, AUC 0.797), as well as NT-proBNP (cut-off 537 pg/ml, AUC 0.799 and cut-off 1010 pg/ml, AUC 0.768, respectively) and norepinephrine (cut-off 454 pg/ml, AUC 0.716 and cut-off 575 pg/ml, AUC 0.783, respectively). CONCLUSION: Haemodynamic impairment (as indicated by BNP and NT-proBNP plasma values) and sympathetic activation predict exercise capacity and ventilatory efficiency in HF patients.     

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.     

A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients.

BACKGROUND: Angiotensin converting enzyme inhibitors at high doses have been shown to improve prognosis of heart failure patients. Their beneficial effects on exercise capacity have been less convincing in large parallel group studies. The objective of this investigation was to explore the mechanisms involved in dose-related functional effects and to test the hypothesis that a trial recommended high dose of lisinopril would improve aerobic exercise capacity and cardiovascular function more than with a low dose. METHODS: Twelve patients with symptomatic heart failure completed a randomized double-blind crossover trial of lisinopril 5 mg o.d. and 20 mg o.d. for 24 weeks, crossing over the doses at 12 weeks. The primary end-point was aerobic exercise capacity, and the secondary end-points were cardiac performance at peak exercise and dobutamine stimulation. RESULTS: The aerobic exercise capacity (primary end-point) was significantly higher during the 5mg per day dosage compared to the 20 mg (1696 vs 1578 ml.min(-1), P=0.016), equivalent to a rise of 1.53 ml.kg(-1)min(-1) from the 19.6 ml.kg(-1)min(-1) with 20mg when normalized by body weight. Seventy-three percent of patients showed greater peak oxygen consumption and peak cardiac power output with the 5mg per day dose than the 20 mg, and none showed the opposite. In terms of cardiac performance, although the results were not statistically significant, there was a consistent pattern showing the same directional changes in favour of the lower dose in peak exercise cardiac power output and cardiac power output at maximal dobutamine. There were no significant differences in the resting values. A total of 24 adverse reactions were reported during the 5 mg phase compared to 38 during the 20 mg phase. CONCLUSIONS: Contrary to expectation, the aerobic exercise capacity of patients was found to be greater with the lower dose of lisinopril, suggesting that therapy with ACE inhibitors for heart failure may require tailoring the doses to the individual to optimize functional benefits in relation to the assumed prognostic benefits.     

A neural network approach to predicting outcomes in heart failure using cardiopulmonary exercise testing

Objectives

To determine the utility of an artificial neural network (ANN) in predicting cardiovascular (CV) death in patients with heart failure (HF).

Background

ANNs use weighted inputs in multiple layers of mathematical connections in order to predict outcomes from multiple risk markers. This approach has not been applied in the context of cardiopulmonary exercise testing (CPX) to predict risk in patients with HF.

Methods

2635 patients with HF underwent CPX and were followed for a mean of 29 ± 30 months. The sample was divided randomly into ANN training and testing sets to predict CV mortality. Peak VO₂, VE/VCO₂ slope, heart rate recovery, oxygen uptake efficiency slope, and end-tidal CO₂ pressure were included in the model. The predictive accuracy of the ANN was compared to logistic regression (LR) and a Cox proportional hazards (PH) score. A multi-layer feed-forward ANN was used and was tested with a single hidden layer containing a varying number of hidden neurons.

Results

There were 291 CV deaths during the follow-up. An abnormal VE/VCO₂ slope was the strongest predictor of CV mortality using conventional PH analysis (hazard ratio 3.04; 95% CI 2.2–4.2, p < 0.001). After training, the ANN was more accurate in predicting CV mortality compared to LR and PH; ROC areas for the ANN, LR, and PH models were 0.72, 0.70, and 0.69, respectively. Age and BMI-adjusted odds ratios were 4.2, 2.6, and 2.9, for ANN, LR, and PH, respectively.

Conclusion

An ANN model slightly improves upon conventional methods for estimating CV mortality risk using established CPX responses.     

心力衰竭患者甲状腺激素改变的临床意义

心力衰竭患者甲状腺激素水平可有明显改变,且心力衰竭越严重,其T3、FT3水平下降与rT3水平升高越明显,而TSH无明显变化.提示甲状腺激素变化或许可以作为判断心力衰竭严重程度的参考指标.     

A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure.

OBJECTIVES: This study was designed to assess the prognostic value of a new variable derived from a cardiopulmonary exercise test, the circulatory power, a surrogate of cardiac power, at peak exercise, in patients with chronic heart failure. BACKGROUND: Peak exercise cardiac power and stroke work are invasive parameters with recently proven prognostic value. It is unclear whether these variables have better prognostic value than peak oxygen uptake (VO(2)). METHODS: The study population comprised 175 patients with chronic heart failure (ejection fraction <45%) who underwent a cardiopulmonary exercise test. Circulatory power and circulatory stroke work were defined as the product of systolic arterial pressure and VO(2) and oxygen pulse, respectively. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS: With a mean follow-up of 25+/-10 months, ejection fraction, heart rate, systolic arterial pressure, peak VO(2), VCO(2), the anaerobic threshold, minute ventilation, the ventilatory equivalents of oxygen and carbon dioxide, the half times of VO(2) and VCO(2) recoveries, and the circulatory stroke work and power predicted outcome. Multivariate analysis demonstrated that the peak circulatory power (chi-square=19.9, P<0.001) (but not peak circulatory stroke work) was the only variable predictive of prognosis. CONCLUSION: The prognostic value of cardiopulmonary exercise tests in heart failure patients can be improved by assessing a new variable, the circulatory power - a surrogate of cardiac power - at peak exercise.     

Abnormal diastolic filling patterns in chronic heart failure--relationship to exercise capacity.

Abnormal patterns of diastolic ventricular filling are well recognized in chronic heart failure, but their relationship to the severity of heart failure is not known. The present study evaluates the relationship of diastolic filling indices to the severity of heart failure and to exercise capacity. In 40 patients with chronic heart failure secondary to ischaemic left ventricular impairment, exercise capacity was measured as peak oxygen consumption (VO2max) by progressive treadmill exercise. Left ventricular function was assessed by M-mode and Doppler echocardiographic indices. Peak aortic velocity correlated weakly with VO2max (R = +0.38, P less than 0.05). VO2max did not correlate with other systolic indices, including mean aortic acceleration, time to peak velocity, or isovolumic contraction time. VO2max correlated with the mitral inflow E/A ratio (R = -0.57, P less than 0.005) and with the Doppler estimate of isovolumic relaxation time (R = -0.48, P less than 0.01). Two distinct patterns of diastolic filling were observed: subjects with mild-to-moderate heart failure (NYHA grade II, VO2max 15-20 ml.kg-1.min-1) had abnormally low E/A ratios and long isovolumic relaxation times, whereas those with severe heart failure (NYHA grade III-IV, VO2max less than 12 ml.kg-1.min-1) had abnormally high E/A ratios and short isovolumic relaxation times. Different patterns of abnormal diastolic filling with different degrees of severity of heart failure may explain some of the previous controversy as to the prevalence of abnormal diastolic function in chronic heart failure. Exercise capacity in chronic heart failure appears more closely related to abnormalities of diastolic filling pattern than to indices of systolic function.     

峰值氧耗量对非射血分数减低的心力衰竭患者预后评估的价值

目的:探讨心肺运动试验重要参数对非射血分数减低心力衰竭(HFr EF)预后评价的价值。方法:前瞻性入组2014年1月到2018年6月,我院诊断为非HFr EF患者,记录患者再入院及死亡事件,最后进行生存分析。结果:入选124例患者,平均随访(24±5)个月,10例患者死亡,32例患者因心力衰竭再住院治疗。心力衰竭组患者峰值氧耗量劣于正常健康对照组[(17.4±2.7)vs.(31.5±3.2)m L·kg^-1·min^-1,P<0.05]。事件组峰值氧耗量低于无事件组[(13.9±2.1)vs.(19.2±3.5)m L·kg^-1·min^-1,P<0.05]。多因素分析表明:峰值氧耗量是预测非HFr EF患者预后的指标(HR=0.81,95%CI:0.76~0.92,P<0.002)。结论:峰值氧耗量可以很好预测非HFr EF患者预后。     

Tissue Doppler imaging adds incremental value in predicting exercise capacity in patients with congestive heart failure

Left ventricular (LV) systolic and diastolic parameters derived from Doppler echocardiography have been used widely to predict functional capacity but diastolic filling is affected by various factors. Tissue Doppler imaging (TDI) that records systolic and diastolic velocities within the myocardium and at the corners of the mitral annulus, has been shown to provide additional information about regional and global LV function. The goal of this study was to examine whether TDI-derived parameters add incremental value to other standard Doppler echocardiographic measurements in predicting exercise capacity. The study enrolled 59 consecutive patients with stable congestive heart failure (CHF). The etiology of heart failure was coronary artery disease in 42 patients and dilated cardiomyopathy in 17. Twenty-three age-matched healthy subjects were recruited as controls. Conventional echocardiographs and TDI were obtained. Early (Ea) and late (Aa) diastolic and systolic (Sa) mitral annulus velocities, the Ea/Aa and E/Ea ratios, were measured by pulsed wave TDI placed at the septal side of the mitral annulus and results were compared with results of cardiopulmonary exercise testing. Systolic and early diastolic velocities of mitral annulus were decreased and the E/Ea ratio was increased in the restrictive group as compared to controls (P = 0.02, P = 0.03, P < 0.001, respectively) but there was no significant difference in late diastolic velocity and the Ea/Aa ratio between the restrictive group and controls. The average peak VO₂ of the patients were 14.9 ± 4.9 ml/min per kg. Achieved peak VO₂ of the patients with E/Ea ratio ≤7.5 was 17.4 ± 5 vs 12.2 ± 3 ml/min per kg for those with E/Ea >7.5 (P < 0.001). Interestingly, the patients with the nonrestrictive pattern and E/Ea ratio >7.5 had reduced exercise capacity, as did the group with restrictive LV filling patterns (12.8 ± 3.3 vs 12.9 ± 4.0 ml/min per kg, P = 0.9). Similarly, there was no significant difference in the mean exercise capacity between the patients with a nonrestrictive pattern vs restrictive pattern with E/Ea ratio ≤7.5 (16.1 ± 5.0 vs 15.4 ± 5.1 ml/min per kg, P = 0.78). Univariate analysis demonstrated that the peak Sa (r = 0.30, P = 0.03), peak Ea (r = 0.38, P = 0.004) and peak Aa (r = 0.35, P = 0.009) correlated significantly with maximum exercise capacity. No relationship was observed between the Ea/Aa ratio and peak VO₂ (r = −0.09, P = 0.48). By multivariate analysis, including age and heart rate, the E/Ea ratio was found to be an independent prognostic factor at peak VO₂ (P < 0.001. In contrast, the comparison of the maximum transmitral early diastolic velocity and the mitral annulus TDI velocity, that is E/Ea ratio, had strong correlation with peak VO₂ (r = −0.46, P < 0.001). Receiver operating characteristic (ROC) analysis was performed for prediction of limited exercise capacity from the E/Ea ratio. An E/Ea ratio ≤7.5 was able to predict peak VO₂ ≤14 ml/min per kg with a sensitivity of 84% and a specificity of 74%. If restrictive pattern or an E/Ea ratio >7.5 was used, 21 out of 24 patients in the reduced exercise capacity group were identified with 16 false positives in the preserved exercise capacity group (P = 0.001). Mitral annular systolic and diastolic velocities of TDI were associated with cardiopulmonary exercise capacity in patients with LV systolic dysfunction. Index of the E/Ea ratio was found to be the most powerful predictor of peak oxygen uptake.     

Incremental shuttle and six-minute walking tests in the assessment of functional capacity in chronic heart failure

BACKGROUND

The incremental shuttle test presents some theoretical advantages over the six-minute walk test in chronic heart failure (CHF), including better standardization and less dependency on collaboration.

OBJECTIVES

The present study evaluated test-retest repeatability, test accuracy in predicting a peak oxygen consumption (VO₂) of 14 mL/kg/min or less, as well as the prognostic value of both walking tests in stable CHF patients.

METHODS

Sixty-three patients (44 men; New York Heart Association functional class II to IV) underwent an incremental treadmill exercise test and, on another day, the walk test in duplicate.

RESULTS

Patients showed well-preserved functional capacity according to the distance walked in both tests (six-minute walk test 491±94 m versus incremental shuttle walk test 422±119 m; P<0.001). Interestingly, the six-minute and incremental shuttle walk test differences in distance walked were higher in more disabled patients. The mean bias ±95% CI of the within-test differences were similar (7±40 m and 8±45 m, respectively). Peak VO₂, but not distance walked in either test, was associated with survival (P<0.05).

CONCLUSIONS

The incremental shuttle walk test showed similar repeatability and accuracy in estimating peak VO₂ compared with the six-minute walk test in CHF patients. Direct measurement of peak VO₂, however, remains superior to either walking test in predicting survival – at least in patients with well-preserved functional capacity.