We performed a prospective study in adult patients with inoperable CTEPH scheduled for BPA. Each patient agreed to participate in this non-interventional prospective cohort study. Patients with CTEPH followed up at the Pasteur University Hospital, Nice, France, between March 2020 and February 2021 were included in the study if they were eligible to BPA (either contra-indication/recusal for pulmonary endarterectomy or patient refusal). All patients had undergone right cardiac catheterization which confirmed pulmonary hypertension with normal wedge pressure, a ventilation/perfusion scintigraphy and an injected chest CT scan confirming the post-embolic origin of the pulmonary hypertension. Informed consent was obtained from all patients. This study conformed to the Declaration of Helsinki.
BPA procedures and right heart catheterization
The BPA procedures were all performed via the femoral vein under a simple local anesthesia (xylocaine 2-4 cc) with no further medication. A 7 French sheath was placed in the femoral vein. The venous sheath was then exchanged for a 70cm shuttle sheath Raabe Flexor (Cook Medical, Bloomington, USA) guided by a long 260cm exchange length 0.035 Starter (Boston Scientific, Marlborough, USA) inch wire and a 6F Launcher Judkins right (Medtronic, Minneapolis, USA) or multipurpose probe (Terumo, Tokyo, Japan) to advance it into the pulmonary artery. PAP was then measured in the pulmonary artery trunk. Vessels were then wired with a BMW (Abbott Vascular, Santa Clara, USA) wire or a Pilot 50 wire (Abbott Vascular, Santa Clara, USA). The lesions to treat were balloon dilated with a 2 to 5 mm x 20 mm Trek balloon (Abbott Vascular, Santa Clara, USA) inflated to between 2 and 8 atmospheres or a 6-8 mm x 20 mm x balloon Rx MUSSO (Terumo, Tokyo, Japan). Selective angiography with 1:1 mixture of saline and contrast agent (Xenetix, Guerbet, France). PAP was once again measured in the pulmonary artery at the same site than the initial measure. No sedation was used. Oxygen was supplied via nasal cannula when necessary (O2 Sat <92%). Saturation was monitored non-invasively. A typical BPA session lasted 1.5 to 2 h. Each session could not exceed 2000 mGy radiation exposure, 45 minutes fluoroscopy time and 200 ml contrast medium.
The angioplasty sessions that the study focused on could be first sessions or sessions in progress of BPA treatment that has already begun. BPA procedures were a first one in 16 cases, a second one in 26 cases, a third one in 26 cases, a fourth or more one in 15 cases. Sixteen patients had 3 procedures during the study. BPA results were characterized according to the Inami classification which takes into account the improved arterial flow of the treated vessels and the improvement or reappearance of the venous flow [16].
Oral anticoagulation, mainly non-vitamin K antagonist oral anticoagulants: Rivaroxaban or Apixaban which are our chosen anticoagulation option in CTEPH, was discontinued 36 hours before each procedure [17]. The majority of patients did not need cardiology intensive care unit monitoring and returned to their cardiology ward. Some of then (45%) were discharged on the same day. Patients with an uncomplicated procedure resumed their anticoagulant treatment the morning after the procedure. Repeated sessions were performed on average 14 days later. Most patients were in the WHO functional class II or III. All treatments (except anticoagulant therapy) were unchanged during the hospitalization. Especially, modification in diuretic therapy were avoided. When patients were treated with PH targeted drugs (mainly soluble guanylate cyclase stimulator) the dosage did not change during the period of BPA procedures.
Biological measurements
For each BPA procedure, BNP plasmatic dosage were performed before and 24-hours after BPA. BNP was measured using the Alere Triage BNP kit (Beckman Coulter®). The positivity threshold was 100 pg/ml.
ET-1 was assessed in a subset 16 procedures. An ET-1 assay sample was taken as soon as the venous sheath was placed in the main pulmonary artery and again at the end of the procedure. The ET-1 samples were placed on ice and immediately carried to the laboratory. ET-1 assays were performed using the QuantiGlo Human Endothelin-1 kit (ELISA) (R&D systems, Biotechne, MN, USA).
Statistics:
Data characterized by a normal distribution are expressed as mean ± standard deviation while others are expressed as median with maximum and minimum ranges.
The effect of BPA was tested in two ways.
1) For each parameter, the number of increases was compared to the values predicted by a binomial distribution assuming a 50% probability of achievement.
2) The equality of the mean values before and after BPA was tested using a Student's t test on paired series. The PAP values were assumed to be distributed normally. For the assays, for which the standard deviation is proportional to the mean, the tests focused on the logarithm of the values. Computations were made on an Excel spreadsheet.
Data were considered significant at P < 0.05.