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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Longitudinal Assessment of Exercise Capacity via Cardiopulmonary Exercise Testing in Heart Failure Patients with Improved and Persistently Reduced Ejection Fraction: Results from the IMPRO2VEMENT-HF Study

  • Diana Ladera-Santos1,2
  • José López-Aguilera1,2,3,4
  • Jesús Alberto Torres-Zamudio1,2,4
  • Consuelo Fernández-Avilés1,2,3
  • Jorge Perea-Armijo1,2
  • Guillermo Gutiérrez Ballesteros1,2
  • Gloria Heredia Campos1,2,4
  • Luis Carlos Maestre Luque1,2
  • Rafaela Luque López2,3
  • Asunción García Merino2,3
  • Ángela Heredia Torres2,3
  • Juan Manuel García Medina2,3
10 more authors
  • José María Segura Saint-Gerons1,2
  • Álvaro Roldán-Guerra1,2
  • Manuel Crespín-Crespín1,2,3,4
  • Mónica Delgado-Ortega1,2,5
  • Rafael González Manzanares1,2,4,5
  • Dolores Mesa-Rubio1,2,5
  • Manuel Pan-Álvarez Osorio1,2,5
  • Manuel Anguita-Sánchez1,2,4,5
  • Juan Carlos Castillo-Domínguez1,2,4,5
  • Martín Ruiz-Ortiz1,2,5,6
6 affiliations
  1. 1Cardiology Department, Reina Sofia University Hospital, 14011 Cordoba, Spain
  2. 2Cordoba Biomedical Research Institute, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14011 Cordoba, Spain
  3. 3Cardiac Rehabilitation Unit, Cardiology Department, Reina Sofia University Hospital, 14011 Cordoba, Spain
  4. 4Heart Failure Unit, Cardiology Department, Reina Sofia University Hospital, 14011 Cordoba, Spain
  5. 5Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Carlos III Institute of Health, 28029 Madrid, Spain
  6. 6Faculty of Health Sciences, Universidad Internacional Isabel I de Castilla, 09003 Burgos, Spain
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Abstract

Background: Patients with heart failure and reduced ejection fraction (HFrEF) who achieve improved ejection fraction (HFimpEF) after guideline-directed medical therapy exhibit superior prognosis. However, functional impairment remains a hallmark of HF. Aims: To characterize and compare exercise capacity profiles via cardiopulmonary exercise testing (CPET) between patients with HFimpEF and those with persistently reduced ejection fraction (HFprEF) using a baseline-adjusted analysis. Methods: Data from a longitudinal cohort of 111 HFrEF patients with baseline and follow-up CPET data (minimum 6-month follow-up) were analyzed. Patients were stratified into HFimpEF and HFprEF groups, according to the Universal Definition of HF. Changes between groups were evaluated using Analysis of Covariance (ANCOVA) adjusted for baseline values, with non-parametric Bootstrapping (2000 resamples) and multiplicity. Results: We included 111 patients: 69 with HFimpEF (62.2%) and 42 with HFprEF (37.8%). At a median follow-up of 8.7 months, the HFimpEF group showed significantly greater reverse remodeling (adjusted ΔLVEF +19.9%, p < 0.001) and a greater reduction in NT-proBNP levels (−557.6 pg/mL, p = 0.042). Both groups demonstrated intra-group functional improvements. However, in adjusted between-group ANCOVA models, HFimpEF achieved a significantly greater recovery in percentage of predicted peak oxygen consumption (adjusted difference: +8.5%; 95% CI: 1.2 to 16.1; p = 0.021). Net adjusted between-group differences for absolute VO2peak gain, submaximal threshold, ventilatory efficiency and recovery kinetics did not reach statistical significance. Multivariate analysis identified older age (beta −0.261, p = 0.010), diabetes mellitus (beta −0.210, p = 0.023) and baseline VO2peak (beta −0.569, p < 0.001) as negative predictors of improvement. Conclusions: Comprehensive HFrEF management improves exercise capacity across all patients. Although HFimpEF yields superior gains in normalized aerobic capacity, overall functional trajectories are largely comparable between phenotypes. This structural-functional decoupling underscores persistent residual limitations in HFimpEF, supporting CPET for longitudinal risk stratification.

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Cite

BibTeXRIS
BibTeX
@article{laderasantos2026longitudinal,
  title = {{Longitudinal Assessment of Exercise Capacity via Cardiopulmonary Exercise Testing in Heart Failure Patients with Improved and Persistently Reduced Ejection Fraction: Results from the IMPRO2VEMENT-HF Study}},
  author = {Diana Ladera-Santos and José López-Aguilera and Jesús Alberto Torres-Zamudio and Consuelo Fernández-Avilés and Jorge Perea-Armijo and Guillermo Gutiérrez Ballesteros and Gloria Heredia Campos and Luis Carlos Maestre Luque and Rafaela Luque López and Asunción García Merino and Ángela Heredia Torres and Juan Manuel García Medina and José María Segura Saint-Gerons and Álvaro Roldán-Guerra and Manuel Crespín-Crespín and Mónica Delgado-Ortega and Rafael González Manzanares and Dolores Mesa-Rubio and Manuel Pan-Álvarez Osorio and Manuel Anguita-Sánchez and Juan Carlos Castillo-Domínguez and Martín Ruiz-Ortiz},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15218406},
  url = {https://www.mdpi.com/2077-0383/15/21/8406},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Longitudinal Assessment of Exercise Capacity via Cardiopulmonary Exercise Testing in Heart Failure Patients with Improved and Persistently Reduced Ejection Fraction: Results from the IMPRO2VEMENT-HF Study
AU  - Diana Ladera-Santos
AU  - José López-Aguilera
AU  - Jesús Alberto Torres-Zamudio
AU  - Consuelo Fernández-Avilés
AU  - Jorge Perea-Armijo
AU  - Guillermo Gutiérrez Ballesteros
AU  - Gloria Heredia Campos
AU  - Luis Carlos Maestre Luque
AU  - Rafaela Luque López
AU  - Asunción García Merino
AU  - Ángela Heredia Torres
AU  - Juan Manuel García Medina
AU  - José María Segura Saint-Gerons
AU  - Álvaro Roldán-Guerra
AU  - Manuel Crespín-Crespín
AU  - Mónica Delgado-Ortega
AU  - Rafael González Manzanares
AU  - Dolores Mesa-Rubio
AU  - Manuel Pan-Álvarez Osorio
AU  - Manuel Anguita-Sánchez
AU  - Juan Carlos Castillo-Domínguez
AU  - Martín Ruiz-Ortiz
PY  - 2026
DA  - 2026/10/28
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15218406
UR  - https://www.mdpi.com/2077-0383/15/21/8406
AB  - Background: Patients with heart failure and reduced ejection fraction (HFrEF) who achieve improved ejection fraction (HFimpEF) after guideline-directed medical therapy exhibit superior prognosis. However, functional impairment remains a hallmark of HF. Aims: To characterize and compare exercise capacity profiles via cardiopulmonary exercise testing (CPET) between patients with HFimpEF and those with persistently reduced ejection fraction (HFprEF) using a baseline-adjusted analysis. Methods: Data from a longitudinal cohort of 111 HFrEF patients with baseline and follow-up CPET data (minimum 6-month follow-up) were analyzed. Patients were stratified into HFimpEF and HFprEF groups, according to the Universal Definition of HF. Changes between groups were evaluated using Analysis of Covariance (ANCOVA) adjusted for baseline values, with non-parametric Bootstrapping (2000 resamples) and multiplicity. Results: We included 111 patients: 69 with HFimpEF (62.2%) and 42 with HFprEF (37.8%). At a median follow-up of 8.7 months, the HFimpEF group showed significantly greater reverse remodeling (adjusted ΔLVEF +19.9%, p < 0.001) and a greater reduction in NT-proBNP levels (−557.6 pg/mL, p = 0.042). Both groups demonstrated intra-group functional improvements. However, in adjusted between-group ANCOVA models, HFimpEF achieved a significantly greater recovery in percentage of predicted peak oxygen consumption (adjusted difference: +8.5%; 95% CI: 1.2 to 16.1; p = 0.021). Net adjusted between-group differences for absolute VO2peak gain, submaximal threshold, ventilatory efficiency and recovery kinetics did not reach statistical significance. Multivariate analysis identified older age (beta −0.261, p = 0.010), diabetes mellitus (beta −0.210, p = 0.023) and baseline VO2peak (beta −0.569, p < 0.001) as negative predictors of improvement. Conclusions: Comprehensive HFrEF management improves exercise capacity across all patients. Although HFimpEF yields superior gains in normalized aerobic capacity, overall functional trajectories are largely comparable between phenotypes. This structural-functional decoupling underscores persistent residual limitations in HFimpEF, supporting CPET for longitudinal risk stratification.
SN  - 2077-0383
ER  -