EmPHasis-10 score for the assessment of quality of life in various types of pulmonary hypertension and its relation to outcome

Pulmonary hypertension (PH) is a debilitating pathophysiological disorder, negatively affecting patients’ quality of life (QoL).1 Over the past few years, aspects of health-related quality of life (HRQoL) have emerged as important clinical end points and predictors of prognosis for various cardiovascular disorders.2–7 The emPHasis-10 (E10) score is a novel, short and simple questionnaire for assessing HRQoL in PH patients, and has been designed specifically for use in routine clinical practice.8 The E10 score consists of 10 questions scored in a semantic 6-point scale (from 0 to 5), for a total maximum score of 50 (the higher the score, the worse the quality of life). It has been translated into numerous languages and is in use in many tertiary PH services. However, there is no evidence on the relationship between the E10 score and outcome in the overall PH population and major diagnostic subgroups. We performed a retrospective study, including all patients with a diagnosis of pulmonary arterial hypertension (PAH) or chronic thromboembolic disease (CTEPH) to whom an E10 score was submitted between 2014 and 2017. We assessed the relationship between the E10 score and mortality, both as a single measurement and using repeat assessments. Clinical data were analysed using the Wilcoxon rank sum test and chi-square test. Cox proportional regression analysis was used, with the first E10 score used as the independent variable; multiple E10 scores were used in the modified version of the Cox model, with a ‘start, stop’ mechanism. A total of 2487 E10 questionnaires were administered to 687 patients over 3.7 years. Overall, 239 (34.8%) patients were men, with a mean age of 51.7 ± 18.4 years at first E10 score. Most patients had PAH (556, 80.9%), while 131 (19.1%) patients had CTEPH. Among the patients with PAH, 109 (19.9%) had idiopathic, hereditable or drug-induced PAH; 314 (57.2%) had PAH–congenital heart disease (CHD) and 111 (20.2%) patients had connective tissue disease (CTD). Most patients (408, 62.2%) were in World Health Organization (WHO) functional class III or above. There were no significant differences in terms of the functional class between PAH and CTEPH patients (P = 0.09). However, within PAH, patients with PAH–CHD were more likely to be significantly symptomatic: 54.5% in functional class III or above versus 68.7% in the remainder, P = 0.001. There were 75 (10.9%) patients with Down syndrome, all of whom had PAH–CHD. The average E10 score (first E10) was 25.3 ± 12.7 and was no different in PAH versus CTEPH patients (P = 0.65). Patients with CHD had lower E10 scores (23.2 ± 11.9) compared to other PAH patients (28.2 ± 13.1, P < 0.0001). Over a median follow-up of 2.1 years, 87 patients died. Of these, 77 had PAH and 10 had CTEPH. The first E10 score was significantly associated with mortality (hazard ratio (HR) per 10-unit increase 1.53, 95% confidence interval (CI) 1.27–1.83, P < 0.0001) in the overall population. The E10 score was a significant predictor of death in PAH (HR per 10-unit increase 1.59, 95% CI 1.31–1.94, P < 0.0001), but not in CTEPH (HR per 10-unit increase 1.26, 95% CI 0.77–2.06, P = 0.37). Within PAH, the E10 score taken as a continuous variable was significantly related to mortality in CHD (HR per 10-unit increase 1.42, 95% CI 1.06–1.91, P = 0.02) but not in CTD (HR per 10-unit increase 1.00, 95% CI 0.71–1.42, P = 0.99), with a trend in idiopathic/hereditable/drug-induced PAH (HR per 10-unit increase 1.63, 95% CI 0.97–2.75, P = 0.07). Threshold analysis identified an E10 score of 32 as an optimal cut-off for predicting outcome in idiopathic/hereditable/drug PAH patients and this was also true for CHD patients (Figure 1). The E10 score was a predictor of outcome in PAH, even when adjusting for age and functional class: the E10 score stayed in the model (HR per 10-unit increase 1.27, 95% CI 1.03–1.56, P = 0.03), while WHO was not significant (P = 0.07). Using repeat E10 scores in a start–stop Cox model, the E10 score was a significant predictor of death in the overall PH population (HR per 10-unit increase 1.62, 95% CI 1.35–1.94, P < 0.0001), idiopathic/hereditable/drug-induced PAH (HR per 10-unit increase 1.72, 95% CI 1.17–2.51, P = 0.006) and CHD population (HR per 10-unit increase 2.03, 95% CI 1.43–2.88, P < 0.0001), also after excluding Down syndrome patients (HR per 10-unit increase 2.17, 95% CI 1.45–3.26, P = 0.0002), but not in the Down syndrome population (HR per 10-unit increase 1.66, 95% CI 0.80–3.46, P = 0.18). The relation between the emPHasis-10 (E10) score and mortality in patients with CTEPH (a), PAH-CHD (b), PAH-CTD (c), and idiopathic/familial/drug-induced PAH (d). The cut-off of 32 was used for the E10 score, identified as an optimal cut-off for predicting outcome in idiopathic/hereditable/drug PAH and CHD patients. Black line: patients with scores of 0–32. Red line: patients with scores of 33–50. CTEPH: chronic thromboembolic pulmonary hypertension; PAH: pulmonary arterial hypertension; CHD: congenital heart disease; CTD: connective tissue disease; iPAH: idiopathic pulmonary hypertension; Heritable: heritable pulmonary arterial hypertension; Drug: drug-related pulmonary arterial hypertension. In this study, we found that the total E10 score is related to mortality in patients with idiopathic/hereditable/drug-induced and CHD–PAH patients. While there was a significant correlation between the E10 score and WHO functional class, the E10 score was an independent predictor carrying additional prognostic information. The prognostic power of the E10 score applies not only to a single cross-sectional assessment, but its relation to mortality is even stronger when considering repeat assessments. The E10 score is, therefore, a powerful tool, not only for assessing QoL in routine clinical practice, but also as an independent predictor of outcome. The strong association between the E10 score and mortality is likely to reflect the relationship between symptoms and the severity of PH. Indeed, the WHO functional class has been shown to be a strong predictor of outcome in PH.9 However, our multivariable model suggests that the E10 score carries information independent of functional class or age. The E10 score, as a QoL score, covers a significantly wider range of activities and areas of impact of PH compared to the WHO class, which focuses mainly on exercise intolerance.10 Moreover, the WHO functional class is based on a physician’s interpretation of the symptoms described by the patients, and lacks reproducibility.11 We submit that the WHO functional class and the E10 score should be used in a complementary fashion when assessing PH patients and estimating their clinical risk. The lack of association between the E10 score and mortality in the smaller CTEPH and CTD–PAH subgroups may be explained by older age compared to PAH and a higher prevalence of comorbidities in these subgroups, which may influence QoL, but may not be linked directly to the risk of death. Moreover, the clinical progression and prognosis of patients with CTEPH differs from that of patients with PAH, and can be modified by interventions not available to other PH patients. This was a retrospective study performed in a single tertiary centre. The relatively small number of events did not allow extensive multivariable modelling. Finally, in the overall analysis we included E10 scores from patients with Down syndrome who have variable degrees of learning difficulties. For this reason, we repeated our analysis excluding patients with Down syndrome, demonstrating that their inclusion did not influence our results. In conclusion, the E10 score is a powerful tool, not only for assessing QoL in PH patients, but also as a valid outcome predictor in routine clinical practice. Further studies are warranted in larger, multicentre cohorts. The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Drs Dimopoulos and Kempny have received unrestricted educational, travel or research grants from Bayer, Pfizer, Actelion and GSK. Dr Dimopoulos has acted as a consultant to Pfizer, Actelion and GSK. Dr Wort has received honoraria and travel grants from Bayer, Actelion and GSK and research grants from Bayer and Actelion. The remaining authors had no conflicts of interest. The author(s) received no financial support for the research, authorship, and/or publication of this article.