title: Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: The WHOLEi+12 trial.
abstract: BACKGROUND
  Pulmonary arterial hypertension is often associated with skeletal-muscle weakness. The purpose of this randomized controlled trial was to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with this disease.
  
  
  METHODS
  Participants were allocated to a control (standard care) or intervention (exercise) group (n=20 each, 45±12 and 46±11years, 60% women and 10% patients with chronic thromboembolic pulmonary hypertension per group). The intervention included five, three and six supervised (inhospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6-min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g., peak oxygen uptake), health-related quality of life, physical activity levels, and safety.
  
  
  RESULTS
  Adherence to training sessions averaged 94±0.5% (aerobic), 98±0.3% (resistance) and 91±1% (inspiratory training). Analysis of variance showed a significant interaction (group×time) effect for leg/bench press (P<0.001/P=0.002), with both tests showing an improvement in the exercise group (P<0.001) but not in controls (P>0.1). We found a significant interaction effect (P<0.001) for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen uptake (P<0.001), indicating a training-induced improvement. No major adverse event was noted due to exercise.
  
  
  CONCLUSIONS
  An 8-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables.
authors.affiliation: Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: González-Saiz
authors.affiliation: Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fiuza-Luces
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia and Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain; Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, USA. Electronic address: fabian.sanchis@uv.es.
authors.forename: Fabian
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.affiliation: Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain; Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, USA; GIDFYS, European University Miguel de Cervantes, Valladolid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santos-Lozano
authors.affiliation: Pulmonary Hypertension Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Quezada-Loaiza
authors.affiliation: Pulmonary Hypertension Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Flox-Camacho
authors.affiliation: Department of Sports and Computer Science, Section of Physical Education and Sports, Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Munguía-Izquierdo
authors.affiliation: GENUD Toledo Research Group, Universidad de Castilla-La Mancha, Toledo, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ara
authors.affiliation: Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain; Department of Sports and Computer Science, Section of Physical Education and Sports, Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santalla
authors.affiliation: Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Morán
authors.affiliation: Pulmonary Hypertension Unit, Department of Rehabilitation, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Sanz-Ayan
authors.affiliation: Pulmonary Hypertension Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Escribano-Subías
authors.affiliation: Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain; European University, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001945:Breathing Exercises / Q000379:methods*; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000534:rehabilitation*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D055070:Resistance Training / Q000379:methods*; D012132:Respiratory Muscles / Q000503:physiopathology*; D012189:Retrospective Studies; D055815:Young Adult
keywords: Cardio-pulmonary exercise testing; NT-proBNP; Pulmonary disease; Resistance exercise; VO(2peak)