Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial.

AIMS: The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. METHODS AND RESULTS: Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control -0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training. CONCLUSION: Low-dose exercise training at 4-7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results.

Reference ranges for and determinants of right ventricular area in healthy adults by two-dimensional echocardiography.

BACKGROUND: The right ventricular (RV) area is important for diagnosis and follow-up in patients with various diseases, such as in pulmonary hypertension. OBJECTIVES: The aim of this study was to define the reference ranges of the end-diastolic RV area in healthy adults and to assess the determining factors. METHODS: In the first part of the study 860 healthy subjects (37.6% female; mean age 28 ± 5.84; 395 endurance athletes, 255 strength athletes and 210 non-athletes) were prospectively assessed. In the second part we performed a pooled analysis of studies published between 1979 and 2014 describing the RV area in healthy subjects (n = 5,248). Statistical analysis included the calculation of reference ranges and the analysis of determining factors. RESULTS: Mean end-diastolic RV areas in 860 healthy subjects were significantly larger in endurance athletes (25.1 ± 2.0 cm(2)) compared with strength athletes (22.9 ± 1.7 cm(2)) and non-athletes (16.7 ± 2.0 cm(2), p < 0.001). In the synopsis of both data sets, mean end-diastolic RV area was significantly larger in European/American males (17 cm(2)) compared with females (14 cm(2), p < 0.001) and in Asian males (16 cm(2)) compared with females (13 cm(2), p < 0.001). The area increased with body surface area and older age. CONCLUSION: This is the largest data set to define RV size in healthy adults aged <50 years. RV area was determined by age, gender, body surface area, ethnicity and high-level exercise training. High standard deviations resulted in high values for the upper limit of the reference range, which might therefore not be useful as cut-off values for screening purposes. Gender- and ethnicity-specific reference ranges should be used. Further studies in subjects aged >50 years as well as in children are needed.

Reference values for and determinants of right atrial area in healthy adults by 2-dimensional echocardiography.

BACKGROUND: Right atrial (RA) size is important in screening, diagnosis, and follow-up assessment in patients with pulmonary hypertension. The objective of this study was to define normal reference values for RA area by echocardiography in a large population of athletic versus sedentary healthy subjects. METHODS AND RESULTS: In the first part of the study, 880 healthy adult subjects (mean age, 28±6 years; 38% women; 395 top-level endurance athletes, 255 strength athletes, and 230 nonathletes) were prospectively assessed. In the second part, we performed a pooled analysis of all studies published between 1976 and 2011 describing RA area in healthy subjects (n=624). Statistical analysis included the calculation of 95% quantiles for defining cutoff values. Mean RA area in the 880 subjects was significantly larger in endurance athletes compared with the strength athletes and nonathletes. RA area correlated significantly with age, sex, body surface, and endurance training. In a synopsis of both data sets, 95% quantiles for RA area in strength atheletes and nonathletes were 15.2 cm(2) (95% confidence interval, 14.7-15.7) in women and 16.2 cm(2) (95% confidence interval, 15.8-16.6) in men. CONCLUSIONS: To the best of our knowledge, this is the largest data set to describe RA size in adult healthy subjects (age <50 years). Cutoff values for RA area were significantly different in women (15 cm(2)) and men (16 cm(2)). Age, sex, body surface area, and high-level endurance training were determinants of RA area.