EmPHasis-10 health-related quality of life score predicts outcomes in patients with idiopathic and connective tissue disease-associated pulmonary arterial hypertension: results from a UK multicentre study.

Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure.1745 patients with idiopathic PAH (IPAH), drug-induced PAH (DPAH), heritable PAH (HPAH) (collectively "(I/D/H)PAH"), or connective tissue disease-associated PAH (CTD-PAH), who had completed emPHasis-10 questionnaires at one of six UK referral centres between 2014 and 2017, were identified. Correlations with exercise capacity and World Health Organization (WHO) functional class were assessed, and exploratory risk stratification thresholds were tested.Moderate correlations were seen between emPHasis-10 scores and 6-min walk distance (r=-0.546), incremental shuttle walk distance (r=-0.504) and WHO functional class (r=0.497) (all p<0.0001). Distribution of emPHasis-10 score differed significantly between each WHO functional class (all p<0.0001). On multivariate analysis, emPHasis-10 score, but not WHO functional class, was an independent predictor of mortality. In a risk stratification approach, scores of 0-16, 17-33 and 34-50 identified incident patients with 1-year mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO functional class III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis-10 scores had improved exercise capacity (p<0.0001) and patients who transitioned between risk groups demonstrated similar survival to patients originally in those risk groups.The emPHasis-10 score is an independent prognostic marker in patients with (I/D/H)PAH or CTD-PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.

Social deprivation in Scottish populations with pulmonary hypertension secondary to connective tissue disease and chronic thromboembolic disease.

Socioeconomic factors have been shown to have an adverse impact on survival in some respiratory diseases. Studies from the USA and China have suggested worse survival in idiopathic pulmonary arterial hypertension in low socioeconomic groups. We looked at the effect of deprivation on the outcomes in patients with connective tissue disease-associated pulmonary hypertension (CTDPH) and chronic thromboembolic pulmonary hypertension (CTEPH) in a retrospective observational study. Data were obtained from 232 patients with CTDPH and 263 with CTEPH who were under the care of the Scottish Pulmonary Vascular Unit, Glasgow, UK. We used Cox proportional hazards regression to assess for a relationship between deprivation and survival. We found no difference in survival across deprivation quintiles in the CTDPH (p=0.26) or CTEPH cohorts (p=0.18). We constructed multivariate models using enrolment time, age, sex and body mass index, with no significant change in findings. There was no difference between expected and observed population distribution of CTDPH (p=0.98) and CTEPH (p=0.36). Whilst there was no difference in presenting functional class in the CTDPH group, the CTEPH patients in more deprived quintiles presented in a worse functional class (p=0.032). There was no difference between quintiles of CTEPH patients who had distal or proximal disease (p=0.75), or who underwent surgery (p=0.5). Increased social deprivation is not associated with worse survival in patients with CTDPH and CTEPH managed in the Scottish National Health Service. Whilst there is no evidence of referral barriers in CTDPH, this may not be the case in CTEPH, as lower deprivation was associated with worse functional class at presentation.

Understanding longitudinal biventricular structural and functional changes in a pulmonary hypertension Sugen-hypoxia rat model by cardiac magnetic resonance imaging.

Cardiac magnetic resonance-derived ventricular variables are predictive of mortality in pulmonary arterial hypertension. Rodent models which emphasize ventricular function, allowing serial monitoring, are needed to identify pathophysiological features and novel therapies for pulmonary arterial hypertension. We investigated longitudinal changes in the Sugen-hypoxia model during disease progression. Sprague Dawley rats (n = 32) were divided into two groups. (1) Sugen-hypoxia: a dose of subcutaneous Sugen-5416 and placed in hypobaric hypoxia for two weeks followed by normoxia for three weeks. (2) Normoxia: maintained at normal pressure for five weeks. Rats were examined at five or eight weeks with right-heart catheter, cardiac magnetic resonance, and autopsy. Compared to normoxic controls (23.9 ± 4.1 mmHg), right ventricular systolic pressure was elevated in Sugen-hypoxia rats at five and eight weeks (40.9 ± 15.5 mmHg, p = 0.026; 48.9 ± 9.6 mmHg, p = 0.002). Right ventricular end-systolic volume index was increased in eight weeks Sugen-hypoxia (0.28 ± 0.04 µlcm-2, p = 0.003) compared to normoxic controls (0.18 ±0.03 mlcm-2). There was progressive dilatation of the right ventricular at eight weeks Sugen-hypoxia compared to normoxic controls (0.75 ± 0.13 µlcm-2 vs 0.56 ± 0.1 µlcm-2 p = 0.02). Ventricle mass index by cardiac magnetic resonance at five weeks (0.34 ± 0.06, p = 0.003) and eight weeks Sugen-hypoxia (0.34 ± 0.06, p = 0.002) were higher than normoxic controls (0.21 ± 0.04). Stroke volume, right ventricular ejection fraction, and left ventricular variables were preserved in Sugen-hypoxia. Ventricular changes during the course of illness in a pulmonary arterial hypertension rodent model can be examined by cardiac magnetic resonance. These changes including right ventricular hypertrophy and subsequent dilatation are similar to those seen in pulmonary arterial hypertension patients. Despite the persisting pulmonary hypertension, there are features of adaptive cardiac remodeling through the study duration.

Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension.

Apelin agonism causes systemic vasodilatation and increased cardiac contractility in humans, and improves pulmonary arterial hypertension (PAH) in animal models. Here, the authors examined the short-term pulmonary hemodynamic effects of systemic apelin infusion in patients with PAH. In a double-blind randomized crossover study, 19 patients with PAH received intravenous (Pyr1)apelin-13 and matched saline placebo during invasive right heart catheterization. (Pyr1)apelin-13 infusion caused a reduction in pulmonary vascular resistance and increased cardiac output. This effect was accentuated in the subgroup of patients receiving concomitant phosphodiesterase type 5 inhibition. Apelin agonism is a novel potential therapeutic target for PAH. (Effects of Apelin on the Lung Circulation in Pulmonary Hypertension; NCT01457170).