Chronic thromboembolic pulmonary hypertension: Clinical outcomes

This thesis focuses on clinical outcomes of CTEPH patients treated with PH-specific medical therapy or balloon pulmonary angioplasty (BPA). It provides long-term results of medically treated patients, the first results of BPA treatment in the Netherlands and assesses quality of life (QoL) in CTEPH patients.

In chapter 2 the long-term outcome of CTEPH patients using riociguat is assessed.
After a follow-up of three years, 94% of all patients using riociguat was still alive and 78% of all patients did not experience clinical worsening (all-cause mortality, hospital admission or lower 6-minute walking distance (6MWD) plus lower functional class). In addition, patients using riociguat experienced significant improved functional class, exercise tolerance (measured with 6MWD) and lower NT-proBNP compared to measurements before the start of PH-specific medical therapy.

In chapter 3 long-term results of CTEPH patients using macitentan are described.
CTEPH patients using macitentan were divided in two groups: one group with technical inoperable disease and another group with clinical inoperable disease. Patients in the first group had distal lesions unsuitable for PEA, while patients in the latter group were inoperable due to comorbidities or were reluctant to undergo PEA. Survival rates two years after the start of treatment with macitentan were 86% and 100% for the technical and clinical inoperable CTEPH patients respectively. Both groups had significant improved 6MWD, while 30% of all patients experienced non-severe adverse events.

In chapter 4 the outcomes between CTEPH patients using macitentan and bosentan are compared.
In our cohort, survival and improvements in functional class, NT-proBNP and 6MWD of patients using macitentan were similar compared to patients using bosentan. Significant baseline predictors of survival were right atrial pressure, cardiac output and lowest saturation during 6MWD.

In chapter 5 outcomes of CTEPH patients using PH-specific medical monotherapy are compared with CTEPH patients using PH-specific medical combination therapy.
In our study, patients starting combination therapy had more severe disease at baseline, but survival up to five years after start of therapy was similar in both groups.

In chapter 6 the first results of BPA in the Netherlands are reported.
Our study includes data of 38 CTEPH patients who underwent 172 BPA procedures. There was a significant improvement of functional class, 6MWD and pulmonary hemodynamics. Non-severe complications occurred in 12% of all procedures.

In chapter 7 results of change in ventilation/perfusion (V/Q) scan after BPA treatment are presented.
A V/Q scan was performed in 20 CTEPH patients at baseline and 6 months after completion of BPA treatment. Both visual assessment and a semi-quantitative calculated pulmonary vascular obstruction index showed perfusion improvement. Nevertheless, the improvement of perfusion did not correlate with clinical outcome.

In chapter 8 we reported longitudinal follow-up results of the use of the EmPHasis-10 and CAMPHOR questionnaires in CTEPH and PAH patients.
We showed a significant reduction in scores of both the EmPHasis-10 and CAMPHOR (quality of life and symptoms) domains after one year of treatment. In addition, the EmPHasis-10 score showed a good correlation with the scores of all CAMPHOR domains.