This study showed that QoL, as measured with the disease-specific scale emPHasis-10, remained impaired in CTEPH patients with normalised haemodynamics after BPA. While the QoL score was associated with 6MWD, it was not associated with haemodynamic parameters. The administration of HOT was also associated with impaired QoL. Among patients with HOT, the QoL score was associated with 6MWD.
EmPHasis-10 in patients with PH
A previous validation study of emPHasis-10, which included patients with CTEPH, was
conducted by Takeyasu et al.12 in Japan. The emPHasis-10 total score was 19.4 ± 10.6 points; scores were increased with higher World Health Organisation (WHO) functional classes (I, 5.0; II, 17.0 ± 1.4; III, 24.1 ± 2.2; and IV, 39.5 ± 2.5). These results were consistent with those of the original emPHasis-10 report by Yorke et al.,11 which was based on patients in the United Kingdom and Ireland. The median emPHasis-10 total score was 14 (8–24) points, which corresponded to the midpoint between WHO functional classes I and II.11, 12 This implied that QoL was not completely equivalent to WHO functional class I, despite haemodynamic improvement.
Recently, Lewis et al. reported that emPHasis-10 was an independent prognostic marker in patients with either idiopathic pulmonary artery hypertension or connective tissue disease-associated pulmonary artery hypertension, thus emphasising the importance of emPHasis-10 assessment.17 There are limited reports on emPHasis-10 in patients with CTEPH.18 While the majority can be treated by surgical and/or catheter interventions that do not apply to other patients with PH, the clinical progression and prognosis of these patients vary. Thus, further studies are needed to clarify the prognostic utility of emPHasis-10 in patients with CTEPH.
Determinants of QoL in patients with CTEPH
Studies using generic instruments have reported impaired QoL in CTEPH patients with a mean PAP >25 mmHg after treatment.4 Halank et al.19 used the SF-36 questionnaire to assess QoL in patients with severe CTEPH and concluded that mental disorders, exercise capacity, long-term HOT, right heart failure, and age played more important roles in the impairment of QoL than haemodynamic parameters at rest. Kamenskaya et al.20 also used the SF-36 questionnaire and reported impaired QoL even after 1 year of PEA. Urushibara et al.21 found that QoL was also impaired after PEA and medical treatment; physical function items were especially associated with PVR and 6MWD. Using the EuroQol-5 dimensions questionnaire, Minatsuki et al.22 observed impaired QoL after BPA and medical treatment; they also reported a significant correlation with mean PAP and 6MWD.
Generic QoL assessment scales may be unable to assess specific conditions inherent to patients with PH. Therefore, it is necessary to use disease-specific QoL scales that assess factors directly affected by disease pathology and symptoms.23 Several observational cohort studies have demonstrated that haemodynamics and exercise capacity are related to disease-specific QoL in patients with moderate to severe PH. In the original report, which included patients with varying types and severity of PH, emPHasis-10 was shown to have a moderate correlation with 6MWD.11 Among patients with severe PH, including those with CTEPH, the emPHasis-10 score was moderately correlated with both 6MWD and mean PAP.13 Lewis et al.17 reported that the emPHasis-10 score was modestly correlated with 6MWD and weakly correlated with pulmonary haemodynamics in a large cohort with severe PAH of various aetiologies. To our knowledge, the present study is the first to evaluate disease-specific QoL and its determinants among CTEPH patients with a mean PAP <25 mmHg. We demonstrated that the emPHasis-10 score was related to the 6MWD, but not to haemodynamic parameters. These findings suggest that exercise capacity plays a more important role in QoL among CTEPH patients with normalised haemodynamics. Furthermore, emPHasis-10 may be a convenient alternative to the 6MWD as an assessment of exercise capacity in this patient group.
Improvement in QoL
Exercise training has been reported to improve exercise capacity and QoL in patients with PH. Randomised controlled trials24–26 evaluating the efficacy of individually tailored interventions, including exercise therapy and respiratory training, in patients with PH (who were on stable medications) have reported improved exercise capacity, health-related QoL, and cardiopulmonary parameters. A study that prospectively recruited 35 consecutive patients with confirmed invasive and inoperable CTEPH or residual CTEPH27 found that exercise training was associated with improvements in exercise capacity and QoL. Notably, in a recent prospective cohort study of patients with CTEPH after BPA,28 exercise training improved QoL and exercise capacity. Based on our data, it is plausible that exercise training can contribute to an improvement in QOL in CTEPH patients with more normalised haemodynamics; this needs to be evaluated in further studies.
QoL in patients with HOT
The use of HOT was associated with impaired QoL. The following emPHasis-10 sub-items were found to be significantly lower among patients treated with HOT: frustration due to shortness of breath, vitality, shortness of breath on stairs, lack of control over life events due to PH, independent living, and burden on family and friends. This was unexpected, as HOT prevents the progression of PH and improves hypoxemia.29, 30 However, it is consistent with previous studies reporting that HOT decreases QoL.19, 31 Possible factors related to impaired QoL may have included the patients’ perceived restrictions on their daily activities, embarrassment about using O2 with a nasal cannula in public, distress at losing their independence, and worry due to the possibility that their O2 supply would be completely depleted if they were to leave their house.32 We need to be cautious about the unnecessary use of HOT in CTEPH patients with haemodynamic improvement. The use of HOT was associated with impaired haemodynamics, even among patients with a mean PAP <25 mmHg. This highlights the need for further study on whether additional treatment with BPA and/or medication adjustments could facilitate the discontinuation of HOT and lead to further improvement in QoL and physical function.
Study limitations
This study has some limitations. Our study adopted a cross-sectional observational design without a control group. While QoL was assessed, we were unable to verify the patients’ psychological status, housing circumstances, family support, or other social aspects of their daily lives. The potential influence of these factors should be considered in future studies.