Prognostic value and diagnostic potential of cardiopulmonary exercise testing in patients with chronic heart failure

Cardiopulmonary exercise testing (CPET) is a well established technique for stratifying cardiovascular risk in patients with chronic heart failure (CHF). Important prognostic variables include a reduced peak oxygen uptake which has a central use in cardiac transplant selection, and the abnormal relation between minute ventilation (VE) and carbon dioxide production (VCO(2)), often referred to as the elevated VE/VCO(2) slope. We will discuss the pathophysiology of these abnormal responses to exercise in CHF, and how these are interpreted during CPET. The potential of CPET for diagnosing circulatory, respiratory, metabolic, musculoskeletal or mixed limitations is an emerging field of research. We will speculate on how CHF manifests during CPET, and clarify the pathophysiological basis of these exercise responses. To improve our understanding of the diagnostic value of CPET, further investigation is required by clinicians to develop reference ranges for CHF patients from a co-ordinated multicentre approach. The use of CPET technology is becoming increasingly prevalent in cardiology services, and it is likely that, in the future, CPET will take a more prominent role in guiding patient management provision.     

Prognostic value of cardiopulmonary exercise variables in chronic heart failure patients with or without beta-blocker therapy

The prognostic value of exercise-derived variables in the prediction of mortality in patients with chronic heart failure treated by beta blockers continues to be debated. A total of 402 patients with chronic heart failure, including 255 treated with beta blockers, were included and followed for 26 +/- 20 months after the exercise test. On univariate analysis, and in contrast to peak exercise oxygen consumption, the prognostic value of the minute ventilation/carbon dioxide production slope was increased in patients receiving beta-blocker therapy. On multivariate analysis, no independent prognostic variable emerged in patients not on beta-blocker therapy. However, the model that included the circulatory power (peak oxygen uptake x systolic blood pressure), in addition to age, New York Heart Association class, and left ventricular ejection fraction, was the best 1 for patients on beta-blocker therapy. In conclusion, in patients with chronic heart failure, the circulatory power is the exercise variable with the greatest independent prognostic value, compared with the peak exercise oxygen consumption and minute ventilation/carbon dioxide production slope.     

终末期慢性心力衰竭患者运动中摄氧通气效率指标的临床应用

目的 评估心肺运动试验(CPET)摄氧通气效率指标摄氧效率平台(OUEP)、摄氧效率斜率(OUES)、通气量((V) E)/二氧化碳排出量((V)CO2)最低值和(V)E/(V)CO2斜率在监测终末期慢性心力衰竭(CHF)患者心功能和血液动力学状态中的意义.方法 入选2012年10月至2013年9月阜外心血管病医院住院行心脏移植的CHF患者26例.收集临床资料和CPET参数.在行CPET的2周内,进行超声心动图和Swan-Ganz导管检查监测血液动力学参数,并对CPET中摄氧通气效率指标与超声心动图参数和血液动力学参数进行相关性分析.结果 CPET摄氧效率指标OUEP、OUES与传统指标峰值氧耗量(峰值(V)O2)之间相关性好(r=0.535、P＜0.01;r=0.840、P＜0.001).在终末期CHF患者中OUEP相对峰值(V)O2的变化斜率约为32,而OUES相对峰值(V)O2的变化斜率仅约为2,两者相差约16倍,OUEP改变比OUES、峰值(V)O2更加敏感和显著(P＜0.05).OUEP、峰值(V)O2测定值占预测值百分比(％ pred)、(V)E/(V)CO2斜率和(V)E/(V)CO2最低值与无创血液动力学参数峰值心输出量(r =0.535,P＜0.01; r=0.652,P＜0.001; r=-0.640,P＜0.001; r=-0.606,P=0.001)和峰值心脏指数(r=0.556,P＜0.01;r=0.772,P＜0.001; r=-0.641,P＜0.001;r=-0.620,P＜0.001)均显著相关,但与静息状态下有创血液动力学参数心输出量和心脏指数不相关(P＞0.05).峰值(V)O2(％pred)和(V)E/(V)CO2斜率与肺动脉收缩压(r=-0.424,P＜0.05; r=0.509,P＜0.01)和平均肺动脉压力(r=-0.479,P＜0.05;r=0.405,P＜0.05)均显著相关,峰值(V)O2(％pred)还与肺毛细血管楔压显著相关(r=-0.415,P＜0.05),(V)E/(V)CO2斜率与肺血管阻力亦呈显著相关(r=0.429,P＜0.05).结论 CPET摄氧通气效率指标OUEP,可配合传统指标峰值(V)O2、(V)E/(V)CO2最低值、(V)E/(V)CO2斜率等,对CHF患者心功能和血液动力学状态的变化进行更好地监测和评估,以指导终末期CHF患者的临床管理.     

Prognostic value of cardiopulmonary exercise testing in cardiac patients with atrial fibrillation

Parameters obtained from cardiopulmonary exercise testing (CPX) are recognized for their high prognostic value in predicting future cardiac events in cardiac patients. Our group compared the prognostic value of CPX parameters between patients with sinus rhythm (SR) and patients with atrial fibrillation (AF).Peak O2 uptake (VO2), the ratio of the increase in VO2 to the increase in work rate (ΔVO2/ΔWR), and the slope of the increase in ventilation to the increase in CO2 output (VE-VCO2 slope) were obtained from CPX in 72 AF patients and 478 SR patients. The prognostic values of these indices were compared between the two groups.Six cardiac deaths and 25 cardiac events were observed in the AF group and 9 cardiac deaths and 96 cardiac events were observed in the SR group, over a prospective follow-up period of 1,192 days. The percentages of cardiac deaths and cardiac events were higher in the AF group than in the SR group. In a multivariate Cox proportional hazards analysis, peak VO2 was identified as a sole significant predictor of cardiac death and cardiac events in SR patients and VE-VCO2 slope was identified as a sole significant predictor of cardiac death and cardiac events in AF patients.Our results suggest that the VE-VCO2 slope is strongly predictive of future cardiac events in patients with AF and that peak VO2 is strongly predictive of future cardiac events in SR patients.     

Short-term reproducibility of cardiopulmonary measurements during exercise testing in patients with severe chronic heart failure

Eleven men with severe chronic heart failure (peak cardiac index 4.0 ± 0.2 L/m ² /min), six on a heart transplantation waiting list, were prospectively assessed. To determine reproducibility of cardiopulmonary and hemodynamic variables for clinical purposes during ramp bicycle ergometry, the patients underwent two ramp bicycle ergometer tests (3 minutes unloaded, work rate increments of 12.5 W/min) with a 1-week interval between tests. Oxygen uptake (v̇ O ₂ ) carbon dioxide production (v̇ CO ₂ ), and ventilation were measured breath by breath, and calculations were performed to determine gas exchange ratio, oxygen pulse, ventilatory equivalents of oxygen and carbon dioxide, and end-tidal partial pressure for oxygen and carbon dioxide. Additionally, heart rate, blood pressure, and lactate levels were assessed. Measurements were performed at submaximum work rate levels of 25 W, 50 W, and 75 W at ventilatory threshold and at peak work rate. At all measurement points, the coefficient of variation for cardiopulmonary variables was between 1.4% and 7.1% for submaximum work rate levels, between 1.2% and 4.4% at ventilatory threshold, and between 2.4% and 7.1% at peak work rate. For heart rate, blood pressure, and lactate levels, coefficient of variation was between 2.7% and 5.7% for submaximum work rate levels, between 1.4% and 6.1% at ventilatory threshold, and between 1.2% and 5.5% at peak work rate. The data suggest high reproducibility for duplicate measurements of cardiopulmonary and hemodynamic variables during ramp bicycle ergometry in patients with severe chronic heart failure. The results may be used to determine whether any variable in a single patient is significantly different from that obtained in a previous exercise test or if the change is within experimental error. (Am Heart J 1997;134: 20-6.)     

心肺运动试验在慢性心力衰竭预后评估中的价值

心肺运动试验通过测定机体对运动的反应,可以评估包括心血管、肺、骨骼肌等多系统的功能和储备,显示出其独特的优势,特别是对于慢性心力衰竭患者的功能状态及预后能够进行客观定量的评估,具有极其重要的价值和意义。本文重点阐述心肺运动试验主要指标的意义及其在慢性心力衰竭预后评估中的价值。     

Prognostic value of time-related changes of cardiopulmonary exercise testing indices in stable chronic heart failure: a pragmatic and operative scheme.

BACKGROUND: Although peak oxygen consumption (VO2) is an objective measurement of functional capacity linked to survival, most clinicians use clinical history to monitor changes over time of functional disability. The aim was to verify the prognostic value of time-related changes (Delta) of symptom-limited cardiopulmonary exercise testing (CPX) indices in stable chronic heart failure (CHF). DESIGN AND METHODS: We studied 231 stable CHF patients (200 men) with left ventricular ejection fraction (LVEF) of 24 +/- 8% and peak VO2 of 14.3 +/- 8 ml/kg per min, who performed two symptom-limited CPX over time. RESULTS: The two incremental CPX were separated by a mean interval of 258 +/- 42 days; 59 (26%) suffered cardiovascular death or underwent urgent heart transplantation during the follow-up (1167 +/- 562 days). Peak VO2, LVEF (measured at second evaluation), Deltapeak VO2 and DeltaNYHA (New York Heart Association classification) were selected as independent predictors in the total population, and LVEF, Deltapeak VO2, and NYHA in patients with peak VO2 of 14 ml/kg per min or less (106 patients); no Delta parameter was selected in patients with preserved exercise tolerance. Survival analysis was performed taking into consideration the inter-test variability of peak VO2 (6%): true fall: more than 6% decrease, decline within the measurement variability; less than 6% decrease, improvement within the measurement variability; less than 6% increase and true rise; more than 6% increase: total mortality rate was 51, 23, 19 and 14% (P < 0.0001), respectively. CONCLUSIONS: Deltapeak VO2 is a useful outcome index; a combination of static (single) and time-related functional variables can enhance the prognostication process in stable CHF patients.     

低钠血症对慢性心力衰竭患者预后的影响

目的：探讨低钠血症对慢性心力衰竭（CHF）患者预后的影响。方法：按血钠水平86例CHF患者被分为正常血钠组（52例）和低钠血症组（34例），按常规CHF治疗后，比较两组左室射分数（LVEF）、CHF纠正时间和死亡率。结果：与正常血钠组比较，低钠血症组LVEF显著降低，心力衰竭纠正时间显著延长．死亡率显著升高（P均〈0.05）。结论：低钠血症是CHF患者影响预后的重要影响因素。     

Prognostic significance of cardiopulmonary exercise testing for 10-year survival in patients with mild to moderate heart failure

Although a number of studies have investigated the prognostic significance of exercise variables, they have focused only on short-term prognosis in relatively severe heart failure. This study was carried out to determine whether the indices obtained during cardiopulmonary exercise testing have prognostic significance during a 10-year follow-up in mild to moderate heart failure. Three hundred and sixty-four consecutive patients with cardiac disease performed 4 min of 20-W warm-up, followed by a symptom-limited incremental exercise test on a cycle ergometer. In addition to the measurements of peak oxygen uptake (VO2) and gas exchange (anaerobic) threshold, the time constant of VO2 kinetics during the onset of warm-up exercise was calculated using a single exponential equation. Data on mortality were available for follow-up in 260 patients. After 3,331+/-610 days of follow-up, 29 cardiovascular-related deaths occurred. The time constant of VO2 in the nonsurvivors was 76.7+/-43.3 s and was significantly prolonged compared with that of survivors (55.3+/-30.6 s, p=0.001). Peak VO2 and gas exchange threshold were both significantly lower in nonsurvivors than in survivors. Kaplan-Meier survival curves for 10 years of follow-up demonstrated a survival rate of 89.0% for patients with a normal VO2 time constant (< 80 s) and 71.7% for those with a longer time constant (> or = 80 s), showing a significant difference in survival (p=0.0028). Respiratory gas parameters obtained during exercise testing, particularly the time constant of VO2 kinetics, were found to be useful for predicting long-term prognosis in patients with chronic heart failure. These results suggest that cardiopulmonary exercise testing could be more applicable in ambulatory patients with minimal symptoms or minimal functional impairment.     

窦性心率震荡对老年人慢性心功能不全预后的预测价值

目的 探讨窦性心率震荡(HRT)对老年慢性心功能不全(CHF)患者预后的预测价值.方法 选择本院2006年10月至2009年5月住院的老年CHF患者96例,记录其相关临床资料,并进行超声心动图、动态心电图检查.应用相应的分析软件对动态心电图检查结果进行分析,比较不同心功能分级患者窦性HRT指标变化的差异;随访9～28个月,终点事件为患者心源性死亡,采用Logisitc回归法分析窦性HRT、年龄、高血压、糖尿病、心肌梗死、左室射血分数(LVEF)、血管紧张素转换酶抑制剂(ACEI)、β受体阻滞剂对CHF患者死亡的预测能力. 结果 按照震荡初始和震荡斜率结果进行HRT分类,HRT的主要参数正常在心功能Ⅱ级(60.0%)与Ⅲ级(45.0%)者比较差异无统计学意义(χ~2=1.60,P>0.05);心功能Ⅲ级与Ⅳ级者(16.7%)比较差异无统计学意义(χ~2=1.43,P>0.05);但心功能Ⅱ级与Ⅳ级者比较差异有统计学意义(χ~2=9.84,P<0.05),HRT在心功能Ⅳ级组明显减弱.平均随访(18.0±9.6)个月,96例患者中,心源性死亡34例,分析显示CHF患者死亡与HRT、低LVEF(≤45%)、年龄(≥65岁)、糖尿病、心肌梗死及心功能分级相关. 结论 窦性HRT指标对老年人CHF预后有良好的预测能力.     

The value of cardiopulmonary exercise testing and brain natriuretic peptide plasma levels in predicting the prognosis of patients with chronic heart failure

BACKGROUND: A peak VO2 above 14 ml/min/kg at cardiopulmonary exercise testing and brain natriuretic peptide (BNP) levels is used to estimate survival in patients with chronic heart failure (CHF). Limited data, however, exist comparing the prognostic value of both markers simultaneously in patients with mild to moderate CHF. METHODS: We prospectively studied 85 consecutive patients (59+/-13 years, 63 men) with CHF (mean LVEF 26+/-6%). All patients underwent cardiopulmonary exercise testing with determination of peak VO2 and measurement of plasma BNP at rest. The incidence of cardiac decompensation and cardiac death was recorded in the follow-up. RESULTS: During a mean follow-up of 427+/-150 days, four deaths and ten cardiac decompensations occurred. Kaplan-Meier estimates of freedom from clinical events differed significantly for patients above and below the median BNP of 292 pg/ml and also for patients above and below a peak VO2 of 14 ml/min/kg (p<0.05 each). BNP and peak VO2 (area under the ROC 0.75 vs. 0.72) showed a comparable discrimination of CHF patients with adverse cardiac events. The prognostic information of BNP was at least as powerful as that derived from peak VO2. A BNP above 324 pg/ml was associated with a risk ratio of 8.8 for adverse cardiac events. CONCLUSIONS: In patients with mild to moderate CHF, BNP measurements appear to be an alternative to peak VO2 determined by cardiopulmonary exercise testing for the assessment of prognosis in CHF. BNP may facilitate the ambulatory management of patients with mild to moderate CHF since it is less expensive, less time-consuming, and free of procedural risk compared to exercise testing.     

Standardizing and predicting results from cardiopulmonary exercise testing in patients with heart failure

PURPOSE: Cardiopulmonary exercise testing is a common prognostic tool in heart failure, yet it is not standardized. The purpose of this study was to evaluate a means of standardizing oxygen consumption (VO(2)) measurement and to evaluate the ability to predict peak VO(2) from submaximal exercise. METHODS: Fifty consecutive exercise tests with a respiratory exchange ratio > or =1.10 were evaluated. VO(2) was graphed against respiratory exchange ratio and the peak VO(2) was determined with logarithmic, linear, power, and exponential regression lines. To predict a peak VO(2), each patient's submaximal exercise data (respiratory exchange ratio < or =0.98) were fitted to each regression line. The mean of the last 30 seconds of un-averaged breath-by-breath data was used as the reference value. Peak VO(2) assessments are also provided from the metabolic cart, a rolling time average, and the graphical method. RESULTS: Logarithmic regression best standardized peak VO(2). Mean absolute bias (mL x kg x min) was 0.60 +/- 0.44 for logarithmic, 0.61 +/- 0.47 for linear, 0.85 +/- 0.67 for power, and 1.44 +/- 2.22 for exponential. The mean absolute bias between the peak logarithmic predicted VO(2) and the reference peak VO(2) was 1.62 +/- 1.20 mL x kg x min (9.5% of the peak VO(2)). CONCLUSION: Among the methods studied, logarithmic regression analysis was the best method to standardize and predict peak VO(2) in this cohort of patients with heart failure.     

Limited predictive value of cardiopulmonary exercise indices in patients with moderate chronic heart failure treated with carvedilol

Background

Peak oxygen consumption (VO2) is traditionally used for risk stratification in chronic heart failure (CHF); however, its predictive value is unknown with carvedilol treatment. Therefore, we sought to investigate the prognostic role of gas-exchange parameters obtained from symptom-limited cardiopulmonary exercise testing (CPX) in patients with CHF that is treated with carvedilol.

Methods

A total of 508 consecutive patients (443 men, mean age [± SD] 59 ± 9 years) with a mean left ventricular ejection fraction (LVEF) of 25% ± 7% underwent CPX. The peak VO2 was 13.9 ± 3 mL/kg/min; the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO2 slope) was 32 ± 2. Outcomes (cardiovascular death or urgent heart transplantation) were determined when all patients who survived had been observed for a minimum of 6 months.

Results

Patients were divided into groups according to treatment (carvedilol and non-carvedilol); 236 patients were treated with carvedilol (46%), at a mean dose of 25 ±13 mg. The VE/CO2 slope, LVEF, peak VO2, and carvedilol treatment were revealed by means of multivariate analysis to be independent and additional predictors in the total population; VE/VCO2 slope, LVEF, and peak VO2 were revealed to be independent and additional predictors in the patients in the noncarvedilol group (all P <.001); and only peak VO2 was revealed to be an independent and additional predictor in the patients in the carvedilol group (P <.01). In the carvedilol group, mortality rates were 26%, 11%, 10%, and 4% (P <.05) in patients with peak VO2 ≤10 mL/kg/min, >10 to ≤14 mL/kg/min, >14 to18 mL/kg/min, and ≥18 mL/kg/min, respectively. No difference in mortality rates according to peak VO2 or additional outcome indices were identified in the 212 patients with peak VO2 >10 mL/kg/min.

Conclusions

Peak VO2 provides limited predictive information in patients with CHF that is treated with carvedilol, and no additional gas exchange parameter yields supplementary advice.