Author + information
- Oriana Ciani, PhDa,b,∗ (, )
- Massimo Piepoli, MDc,
- Neil Smart, PhDd,
- Jamal Uddin, MSce,f,
- Sarah Walker, PhDa,
- Fiona C. Warren, PhDa,
- Ann D. Zwisler, MDf,g,
- Constantinos H. Davos, PhDh and
- Rod S. Taylor, PhDa,f,g
- aInstitute of Health Research, University of Exeter Medical School, Exeter, United Kingdom
- bCentre for Research on Health and Social Care Management, Bocconi University, Milan, Italy
- cHeart Failure Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
- dSchool of Science and Technology, University of New England, Armidale, Australia
- eDepartment of Cardiac Surgery, Ibrahim Cardiac Hospital & Research, Institute, Dhaka, Bangladesh
- fNational Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
- gDanish Knowledge Centre for Rehabilitation and Palliative Care, University Hospital Odense and University of Southern Denmark, Odense, Denmark
- hCardiovascular Research Laboratory, Biomedical Research Foundation Academy of Athens, Athens, Greece
- ↵∗Address for correspondence:
Dr. Oriana Ciani, Institute of Health Research, University of Exeter Medical School, South Cloisters, St. Luke’s Campus, Heavitree Road, Exeter EX1 2LU, United Kingdom.
Objectives This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL).
Background EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (Vo2peak) or through submaximal tests, such as the 6-min walk test (6MWT).
Methods After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (ρ), R2 at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome.
Results Exercise-based CR is associated with positive effects on EC measured through Vo2peak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (Vo2peak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g., R2 <52%; |ρ| < 0.72). Estimated STE was an increase of 5 ml/kg/min for Vo2peak and 80 m for 6MWT to predict a significant improvement in HRQOL.
Conclusions The study results indicate that EC is a poor surrogate endpoint for mortality and hospitalization but has moderate validity as a surrogate for HRQOL. Further research is needed to confirm these findings across other HF interventions.
Dr. Ciani is funded by a post-doctoral scholarship from the University of Exeter Medical School (Exeter, United Kingdom). All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 22, 2018.
- Accepted March 27, 2018.
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