The purpose of this study is to determine whether cardiac resynchronization therapy with the use of an implanted electronic pacemaker reduces morbidity associated with chronic thromboembolic pulmonary hypertension

Rationale: The clinical severity of right ventricular disease is largely determined by right-to-left ventricular dyssynchrony, i.e., delay of electrical activity between the right and left ventricles. Moreover, in patients with chronic thromboembolic pulmonary hypertension (CTEPH), we found that acute correction of this dyssynchrony by temporary pacing (prior to pulmonary endarterectomy, presently the therapy of choice for CTEPH) results in significant improvement in cardiac output. In this study, we aim to establish whether chronic pacing with the use of implanted pacemakers confers long-lasting improvements in cardiac output and functional class.

Objective: To study whether chronic pacing with implanted pacemakers confers long-lasting improvements in cardiac output and functional class in severely symptomatic CTEPH patients who are not eligible for pulmonary endarterectomy, or those in whom pulmonary endarterectomy has failed.

Study design: Chronic intervention study, double-blinded, randomized, cross-over.

Study population: Adult CTEPH patients who are not eligible for pulmonary endarterectomy, or those in whom pulmonary endarterectomy has failed.

Intervention (if applicable): chronic right ventricular resynchronization therapy (RVRT), i.e., chronic right atrial, right ventricular, and left ventricular pacing with the use of implanted pacemakers.

Main study parameters/endpoints: (Duration of) improvements (in l/min) in cardiac output as measured using Doppler echocardiography, and functional class as measured using 6-minute walking distance (6-MWD), right and left ventricular dimensions and ejection fractions (99mTechnetium scintigraphy), biomarkers for heart failure (serum NT-proBNP levels), and quality of life (SF-36) questionnaire.

Design: Randomized, double-blind, cross-over study with 2 arms of 10 patients each (arms 1 and 2). In arm 1, RVRT is switched on immediately after pacemaker implant, is switched of in week 5, and switched on at the start of week 6 until study end (32 weeks). In arm 2, RVRT is switched at the start of week 5 after pacemaker implant until study end (32 weeks). At various follow-up visits at weeks 1, 4, 5, 6, 8, 12, 16, the main study parameters/endpoints (see previous paragraph) will be assessed.

Inclusion Criteria:

Adult patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy, and those in whom pulmonary endarterectomy has failed

Exclusion Criteria:

None