Pulmonary hypertension in adults with congenital heart disease. Clinical phenotypes and outcomes in the advanced pulmonary vasodilator era.

BACKGROUND: Mortality of pulmonary hypertension associated with congenital heart disease (PAH-CHD) in adults remains high. OBJECTIVES: To identify predictors of death and to assess the impact of treatment on outcome. METHODS: Retrospective, multicenter cohort study of 103 adults with PAH-CHD followed-up for 8.6 ± 4.6 years. Patients were grouped according to underlying shunt type into pre-tricuspid, post-tricuspid and complex. Survival rates were analyzed and predictors of death were investigated with Cox regression models. RESULTS: In the post-tricuspid and complex groups (38 and 37 patients, respectively), the most common clinical PAH-CHD subgroup was Eisenmenger syndrome (76.3% and 59.5%, respectively) whereas, in the pre-tricuspid group (28 patients), 46.5% of patients had small or corrected defects. Overall, 88 patients received vasodilators; 39% required combination-therapy. Overall survival at 10 years was 65%. Mortality was highest in the pre-tricuspid group, FC-III-IV and amongst patients receiving monotherapy (p < 0.050). On multivariate analysis, predictors of poor outcome were pericardial effusion (HR: 4,520 [1,470-13,890]; p = 0,008), oxygen saturation(HR: 0.940 [0,900 - 0,990]; p = 0,018) and genetic syndromes(HR: 3,280 [1,098-9,780]; p = 0,033). CONCLUSIONS: Patients in advanced stages at initiation of treatment were at high risk of death and strong consideration should be given for more aggressive therapy.

Randomized trial of non-invasive ventilation combined with exercise training in patients with chronic hypercapnic failure due to chronic obstructive pulmonary disease.

BACKGROUND: Non-invasive ventilation and exercise training might prove beneficial in the management of COPD patients. OBJETIVE: to compare the combined use of exercise training and non-invasive ventilation with the two interventions separately in chronic respiratory failure due to chronic obstructive pulmonary disease. As primary objective exercise capacity and secondary objectives gas exchange, peripheral muscle strength, BODE index, quality of life and systemic inflammatory response. METHODS: Forty-five patients with severe chronic obstructive pulmonary disease were randomized into three groups for an intervention of 12 weeks: exercise training alone, ventilation alone and combined treatment. We assessed exercise capacity, pulmonary function, BODE index, perception of dyspnoea, quality of life and several biomarkers. RESULTS: All exercise capacity parameters improved after training and the combined treatment. In addition, peripheral muscle strength and six-minute walk distance increased after ventilation. We found differences between the combined group and the ventilation group in submaximal effort and in oxygen consumption. Changes in respiratory function were observed in blood gases that improved after ventilation and the combined treatment, with differences between these groups. BODE index, perception of dyspnoea and quality of life improved in all three groups without differences between groups. Levels of interleukin 8 and tumour necrosis factor α decreased after ventilation, and interleukin 8, C-reactive protein and surfactant protein D decreased after training, while all four of these markers fell after the combined treatment. No differences between groups were found. CONCLUSIONS: The combination of ventilation and exercise training had greater benefits than the separate treatments: improvements were observed in both blood gases and the levels of more biomarkers decreased. In addition, submaximal exercise capacity increased in all groups. The improvements seen in BODE index, perception of dyspnoea and quality of life were similar in all groups.

Components of physical capacity in patients with chronic obstructive pulmonary disease: relationship with phenotypic expression.

BACKGROUND: More accurate phenotyping of COPD is of great interest since it may have prognostic and therapeutic consequences. We attempted to explore the possible relationship between the extent of emphysema, as assessed by high-resolution computed tomography (HRCT), and COPD severity. We also included some study variables involving exercise tolerance evaluation and peripheral muscle strength (PMS) measurement. METHODS: Sixty-four patients with COPD (mean age 64 ± 7 years) were enrolled in a prospective observational cross-sectional study. All patients underwent clinical and functional evaluations: assessment of dyspnea, body mass index (BMI), health status assessment, spirometry testing, and arterial blood gas analysis. The extent of emphysema was graded using HRCT. Functional capacity was evaluated by a cardiopulmonary maximal exercise testing (CPET), the shuttle walking test, and by estimation of PMS. RESULTS: Half of the study patients had an emphysematous phenotype. There was a significant correlation between the score derived from analysis of HRCT images and BMI and respiratory functional parameters, as well as VO(2) max (maximal oxygen uptake) and chest pull 1RM (1 rep max). Compared with subjects with a non-emphysematous phenotype, those with an emphysematous phenotype showed a lower BMI, a reduced PMS, and displayed a lower power at CPET. Significant differences in lung function tests were found for diffusing capacity and hyperinflation. No significant differences in quality of life were observed between the two study groups. CONCLUSIONS: Compared with subjects with a non-emphysematous phenotype, subjects with an emphysematous phenotype has a different profile in terms of BMI, lung function, PMS, and exercise capacity.