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Table of Contents
Year : 2017  |  Volume : 6  |  Issue : 4  |  Page : 20-23

Effect of cardiac training therapy on minute ventilation/carbon dioxide production slope and exercise parameters in patients with severe chronic heart failure in short-time rehabilitation

1 Clinic Rosenquelle, Clinic for Cardiac and Pulmonary, Rehabilitation, Germany
2 Department of Cardiology, Pneumology, Angiology and Intensive Care Medicine, University Hospital Aachen, Aachen, Germany
3 Maastricht University Medical Centre, Maastricht, The Netherlands

Date of Web Publication22-Jan-2018

Correspondence Address:
Dr. Erik C Skobel
Clinic for Cardiac and Pulmonary Rehabilitation, Clinic Rosenquelle, Kurbrunnenstraße 5, 52077 Aachen
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/rcm.rcm_30_17

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Aim: Treatment for patients with severe chronic heart failure (CHF) (NYHA III, ejection fraction (EF) <30%) consists of medical or cardiac device theraphy, or heart transplantation. Cardiac exercise traning (CET) has also been shown to be effective and safe. Even though exercise therapy improves quality of life and exercise capacity, is not commonly used. The determination of the VE/VCO2slope >34 during exercise have been shown to be useful for mortability risk stratification in CHF. This analysis investigated the effects of 3 weeks' cardiac rehabilitation (CR) on exercise parameters and VE/VCO2 slope in CHF patients. Materials and Methods: Data from 35 patients with CHF (age 68 ± 11 years, 3 female, EF 29 ± 7%, maximum oxygen uptake (VO2max) 10.8 ± 2.7 mL/min/kg, NYHA class III, all ischemic heart disease) on optimal medication who underwent CR including aerobic endurance training theraphy combined with low dose local muscle strength for 3 weeks were evaluated retrospectively using 6 -min walking test, echocardiography and exercise testing. Results: All patients showed improvement in NYHA class, improvement in 6-min walking distance (285 ± 113 m to 431 ± 120 m, P < 0.0001), increasing VO2max (10.8 to 12.9 ± 3.2 mL/kg, P < 0.0001) and reduced VE/VCO2-slope (44.8 ± 9 to 37.1 ± 6, P < 0.0001). These was no significant effect on EF (29 ± 8% to 32 ± 11%). Conclusion: CET for 3 weeks in severe CHF is associated with reduced VE/VCO2-slope and improved exercise capacity. Longer and randomized studies are needed to evaluate the role of VE/VCO2-slope in mortality risk stratification during training in CHF.

Keywords: Cardiac rehabilitation, heart failure, monitoring, training

How to cite this article:
Skobel EC, Dreher M, Knackstedt C. Effect of cardiac training therapy on minute ventilation/carbon dioxide production slope and exercise parameters in patients with severe chronic heart failure in short-time rehabilitation. Res Cardiovasc Med 2017;6:20-3

How to cite this URL:
Skobel EC, Dreher M, Knackstedt C. Effect of cardiac training therapy on minute ventilation/carbon dioxide production slope and exercise parameters in patients with severe chronic heart failure in short-time rehabilitation. Res Cardiovasc Med [serial online] 2017 [cited 2023 Feb 6];6:20-3. Available from: https://www.rcvmonline.com/text.asp?2017/6/4/20/223784

  Introduction Top

In chronic heart failure (CHF) with reduced or preserved left ventricular (LV) function, reduced exercise capacity with early fatigue and dyspnea is a hallmark in many patients. Main reasons were muscular deconditioning,[1] deficiencies in peripheral blood flow, and skeletal muscle function and morphology.[2]

Training improves skeletal muscle metabolism, ventilatory control, heart function, autonomic nervous system, and circulation.[3] In Germany, patients with CHF receive 3 weeks' cardiac rehabilitation (CR) at either inpatient or outpatient facilities. These short-term programs have already been shown to influence serum factors involved in ventricular remodeling.[4] To investigate the effects of CR on other parameters, this retrospective analysis of clinical data evaluates the effect of 3 weeks of short-term training in a CR clinic on exercise data and ventilatory patterns measured by cardiac exercise testing (CPX) in patients with severe CHF.

  Materials and Methods Top


Clinic “Rosenquelle” in Aachen, Germany, is a dedicated inpatient CR clinic. The standard CR program contains of 3 weeks of exercise training, lifestyle recommendations, and psychological advice. Most of the patients are transferred from regional hospitals after the initial workup for CHF (echocardiography to confirm CHF diagnosis and determination of LV function).

The Rosenquelle database was screened for patients to include in this retrospective analysis. Those included had a LV ejection fraction (LVEF) of <35% and a peak oxygen uptake (VO2 max) <25 mL/min/kg during CPX at the beginning and the end of CR. All patients had been receiving optimized medical therapy based on the European Society of Cardiology guidelines for ≥6 weeks before starting the CR program and had participated in an inpatient rehabilitation program as part of their clinical treatment strategy.[5] Exclusion criteria were acutely decompensated CHF, use of sedatives or inability to undertake exercise tests because of myocardial ischemia, known lung disease, stroke, the presence of severe associated disease, known depression, or psychotic disorders. All analysis was undertaken after patient discharge.

This retrospective analysis of patient data did not require ethical approval, but all analyses were conducted according to the principles of the Declaration of Helsinki.


All patients underwent standard echocardiography, an ergometer-based CPX, and a 6-min walk test (6MWT) as part of their clinical assessment before CR. These evaluations were repeated at the end of the CR program as part of the clinical routine.

Specifically, LVEF was evaluated using biplane transthoracic echocardiography at the start of training and on the last day at the CR clinic. For the 6MWT, patients were instructed to walk on the floor for 6 minutes; the distance covered was used as a measure of exercise capacity as stated by specific guidelines.[6],[7] The CPX bicycle exercise test was performed as part of routine clinical practice according to specific guidelines before the training program and at the end of CR.[8],[9] Exercise began at 10 W after a 2-min period with no load, followed increments of 10 W/min by ramp protocol. Ventilation per minute, VO2, and carbon dioxide (CO2) production were measured using breath-by-breath gas analysis (Viasys Oxygen, Würzburg, Germany). To exclude significant myocardial ischemia, a 12-lead electrocardiography was continuously recorded and mean blood pressure was measured. The oxygen uptake at the anaerobic threshold (VO2-AT) was determined using the V-slope method. The VO2 max value was defined as the highest value in the terminal phase of exercise.

Training schedule

At the rehabilitation clinic, patients performed aerobic endurance training therapy (interval bicycle training at anaerobic threshold which was adapted to CPX at the beginning of the training)[10] 5 times per week for 3 weeks,[11] combined with low-intensity local muscle strengthening exercises.

Statistical analysis

The values are medians (95% confidence interval) ± standard deviation or medians and interquartile range. The paired t-test was used to compare the differences before and after training with two-tailed P values. The software SAS (SAS 9.2., SAS Institute Inc., Cary, NC, USA) for Windows was used for statistical analysis.

  Results Top

A total of 35 patients were included in the analysis. Baseline characteristics are presented in [Table 1].
Table 1: Baseline patient characteristics

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Cardiac function

The New York Heart Association class improved over 3 weeks of CR [Table 2]. There was no change in LVEF or effect on body mass index [Table 2].
Table 2: Body mass index and cardiac function parameters before and after 3 week's cardiac rehabilitation

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Exercise parameters

Six-min walk distance (6MWD) improved significantly from baseline to the end of CR therapy [Table 3]. Significant improvements from baseline were also seen in maximum watts, VO2 max, VO2-AT, minute ventilation/carbon dioxide production (VE/VCO2) slope, and oxygen pulse [Table 3].
Table 3: Effect of 3 week's cardiac rehabilitation on exercise parameters

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  Discussion Top

To the best of our knowledge, this is the first retrospective analysis to show beneficial effects of inpatient CR training after only 3 weeks. Patients in this analysis showed significantly increased 6MWD, maximum workload, and VO2 max and reduced exercise-induced dyspnea compared with baseline after 3 weeks of CR. Furthermore, training was associated with higher VO2-AT and beneficial effects on VE/VCO2 slope, a prognostic marker for CHF mortality.[12] Interval training was chosen as the exercise strategy in this retrospective analysis. It is associated with reverse LV remodeling and VO2 peak increase compared to moderate continuous training.[13]

Exercise training in CHF is safe and improves health status, exercise capacity, and results in a clinical event reduction.[10],[14],[15] The results of a meta-analysis showed that 6 months of exercise training improved exercise capacity compared with usual care in patients with mild-to-moderate CHF.[16] Exercise training also can improve patients' health-related quality of life.

However, not all studies have shown exercise to have beneficial effects in CHF. In the randomized controlled HF-ACTION trial [17] after adjustment for highly prognostic predictors of the primary endpoint, exercise training was associated with significant in both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization.

Data from a meta-analysis synthesizing the results of different studies determined the effect of aerobic exercise training on prognostic parameters, NT-proBNP levels, and VE/VCO2 slope in 408 patients with systolic CHF.[18] Here, analysis revealed VO2 max and VE/VCO2 slope as significant predictors of cardiac-related mortality and hospitalization. In another retrospective analysis, Sarullo et al. evaluated mortality and hospital admissions in a population of 184 CHF patients over 12 months.[12] CHF patients who died had a lower peak VO2 and steeper VE/VCO2 slope than survivors. Multivariate survival analysis revealed that VE/VCO2 slope added additional value to peak VO2 as an independent prognostic factor.

Another meta-analysis of randomized controlled trials of exercise-based CR in patients [19] showed that hospital admission, but not mortality, was significantly reduced after CR. In addition, exercise capacity showed a standardized mean difference in favor of the exercise group compared with controls. Thus, it appears that the main effect of exercise training in CHF is due to reduced hospital admissions and improved quality of life. Improvements in these parameters may make an important contribution to continued participation in longer CR programs.

The findings of the current retrospective analysis are in agreement with the results of the meta-analyses described above. We showed that both VO2 max and VE/VCO2 slope were significantly decreased by 3 weeks of exercise training during CR. Given the importance of VE/VCO2 slope as a prognostic factor in CHF, it is possible that the short-term benefits associated with 3 weeks of CR in this retrospective analysis might be translated into better long-term outcomes for these patients.

Changes in ventilator parameters during exercise seen in our retrospective analysis were also similar to previous data. McConnell et al.[1] reported that exercise training in CHF improved respiratory muscle endurance and reduced breathlessness. Training had no effect on stroke volume, whereas ventilation and perception of breathing difficulties decreased during exercise.

The long-term pathophysiologic effects of exercise training in CHF remain unclear. Posttraining reductions in tumor necrosis factor-alpha and interleukin-6 levels have been reported after 5 sessions per week of traditional aerobic or resistance exercise,[20],[21] but additional research is needed to better define the mechanisms by which exercise training as part of CR is beneficial in CHF patients.

Retrospective analysis limitations

The most important limitation of retrospective analysis is a lack of randomization to treatment and the absence of a control group. Furthermore, long-term follow-up data on outcomes after CR were not available. However, over the short duration of the analysis, participation of patients in the CR program was monitored and assured. This is in contrast to long-term studies of training in CHF where training is not usually monitored continuously. As a result, poor compliance by participants may contribute to borderline effects on mortality and hospital admission. This was not a problem in our retrospective analysis. Inspiratory muscle capacity is not usually measured during in CR and was not included in this retrospective analysis.

  Conclusion Top

The results of this retrospective analysis show that CR has significant short-term beneficial effects on VE/VCO2 slope and exercise capacity in patients with severe CHF. The effects of these early improvements in prognostic factors on long-term outcomes remain to be determined.


We would like to thank Mrs. Sigrid Gloeggler, Clinical trial Center Aachen, Germany, for the data collection.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

McConnell TR, Mandak JS, Sykes JS, Fesniak H, Dasgupta H. Exercise training for heart failure patients improves respiratory muscle endurance, exercise tolerance, breathlessness, and quality of life. J Cardiopulm Rehabil 2003;23:10-6.  Back to cited text no. 1
Hambrecht R, Schulze PC, Gielen S, Linke A, Möbius-Winkler S, Erbs S, et al. Effects of exercise training on insulin-like growth factor-I expression in the skeletal muscle of non-cachectic patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 2005;12:401-6.  Back to cited text no. 2
Gielen S, Sandri M, Kozarez I, Kratzsch J, Teupser D, Thiery J, et al. Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: The randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging catabolism study. Circulation 2012;125:2716-27.  Back to cited text no. 3
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Sarullo FM, Fazio G, Brusca I, Fasullo S, Paterna S, Licata P, et al. Cardiopulmonary exercise testing in patients with chronic heart failure: Prognostic comparison from peak VO2 and VE/VCO2 slope. Open Cardiovasc Med J 2010;4:127-34.  Back to cited text no. 12
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Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial. JAMA 2000;283:3095-101.  Back to cited text no. 14
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Davies EJ, Moxham T, Rees K, Singh S, Coats AJ, Ebrahim S, et al. Exercise based rehabilitation for heart failure. Cochrane Database Syst Rev 2010;4:CD003331.  Back to cited text no. 16
O'Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1439-50.  Back to cited text no. 17
Cipriano G Jr., Cipriano VT, da Silva VZ, Cipriano GF, Chiappa GR, de Lima AC, et al. Aerobic exercise effect on prognostic markers for systolic heart failure patients: A systematic review and meta-analysis. Heart Fail Rev 2014;19:655-67.  Back to cited text no. 18
Lewinter C, Doherty P, Gale CP, Crouch S, Stirk L, Lewin RJ, et al. Exercise-based cardiac rehabilitation in patients with heart failure: A meta-analysis of randomised controlled trials between 1999 and 2013. Eur J Prev Cardiol 2015;22:1504-12.  Back to cited text no. 19
Smart NA. How do cardiorespiratory fitness improvements vary with physical training modality in heart failure patients? A quantitative guide. Exp Clin Cardiol 2013;18:e21-5.  Back to cited text no. 20
Smart NA, Murison R. Rate of change in physical fitness and quality of life and depression following exercise training in patients with congestive heart failure. Congest Heart Fail 2013;19:1-5.  Back to cited text no. 21


  [Table 1], [Table 2], [Table 3]


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