The present study retrospectively included 47 patients with confirmed CTEPH with CKD who were treated with BPA and admitted to the intensive care unit between December 2012 and September 2020.
Suggested pre- and post-procedural management of the patients was recently published . In brief, clinical examination, echocardiography, 12-lead electrocardiogram, laboratory tests, 6-minute walk tests, computed tomography angiography, right-heart catheterization and pulmonary angiography were assessed for all patients. The final diagnosis of CTEPH was made according to the current guidelines
. All patients were presented in an interdisciplinary CTEPH conference to define the therapeutic concept. BPA was performed as a staged procedure according to standard clinical practice by a dedicated BPA team (interventional radiologist, cardiologist and thoracic surgeon). The interval between each BPA sessions is about 4-8 weeks. Prior to the next BPA procedure, follow-up examinations were performed that were adjusted to the individual requirements of each patient, always including reevaluation of clinical status and laboratory findings. Finally, an in-hospital follow-up examination was performed 6 months after the last BPA procedure.
Right heart catheterization
Right heart catheterization (RHC) was performed as a part of the diagnostic work-up . RHC was routinely performed via the right internal jugular vein using a 6F sheath and a standard Swan-Ganz catheter. Medication of the patients was not modiﬁed before or during RHC; in particular, no vasoactive agents were administered. All patients received pulmonary hypertension therapy, such as Riociguat, phosphodiesterase-5 or endothelin receptor antagonist, according to RHC assessment.
Balloon pulmonary angioplasty
BPA was performed as staged procedure under smooth sedation using femoral or jugular access as previously described (Figure 1) . All patients received anticoagulation with rivaroxaban, which was paused for the intervention day (without low molecular weight heparin bridging). During the procedure, patients received heparin intravenously at 100 IU/kg to maintain an activated clotting time (ACT) >250 seconds. A 6F sheath (Terumo, Tokyo, Japan) was placed in the pulmonary artery, and a 6F guiding catheter (JR 4, Dublin, Ireland) was inserted into the pulmonary artery to selectively intubate the obstructed segmental arteries. The guide-wire (Run-through NS-PTCA, Terumo, Tokyo, Japan) was placed into the sub-segmental arterial branches, passing the obstructing endoluminal material. The sub-segmental branches were then dilated by multiple inﬂations of semi-compliant balloons (Emerge 2.0/15 mm, Boston Scientiﬁc, Marlborough, MA). A ﬁnal ﬂuoroscopy documented the post-procedural morphologicresult.
Blood sampling and laboratory assessment of renal function
Blood samples were collected from cubital veins in all patients who were enrolled in the study. NT-proBNP and troponin I were measured on admission. The level of NT-proBNP in the plasma was measured using an Elecsys NT-proBNP analyzer, a commercially available electrochemiluminescent sandwich immunoassay (Roche Diagnostics GmbH, Mannheim, Germany). CRP levels were measured using a commercially available immunonephelometric kinetic assay (BN ProSpec; Siemens, Tarrytown, NY, USA) using Cardiophase CRP reagents. Other biochemistry measurements were performed using the Jaffe kinetic method on a Hitachi 7600 Autoanalyzer (Hitachi, Ltd., Tokyo, Japan).
Venous blood samples for determination of serum creatinine and serum urea were collected in plain tubes at baseline, prior to and after each BPA procedure, and at the 6-month follow-up. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated modification of diet in renal disease formula and was used as the main parameter for the assessment of chronic renal function . CKD was defined as baseline estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 as assessed by the simplified Modification of Diet in Renal Disease (MDRD) formula: eGFR =186.3 (SCr)−1.154 (age)−0.203 (female: ×0.742) . In accordance with the recommendations of the Acute Kidney Injury Network, acute renal failure was defined as an increase of the serum creatinine of ≥0.3 mg/dL (≥26.4 mmol/L) or to ≥150% from baseline . Contrast-induced renal failure usually occurs within 72 h after exposure . Thus, renal biomarkers were measured prior to, 24, 48 and 72 h after the BPA in this study.
Several prevention strategies have been proposed such as low dose of low osmolar contrast media (Visipaque, GE Healthcare Ireland, Dublin, Ireland), hydration, and nephroprotective drugs during hospitalization. All patients who undergo BPA intervention receive 500 mL saline, 20 mg furosemide and 1g potassium chloride once one day prior to a BPA session, once immediately after BPA and once on the day after the BPA, individually adapted to serum electrolytes if necessary. Patients in the rhBNP group received 0.005 μg/kg/min of rhBNP (Lyophilized Recombinant Human Brain Natriuretic Peptide, Chengdu Nuodikang Biological Pharmaceutical Co. Ltd., China).
Quantitative data were expressed as mean value ± standard deviation, while qualitative data were expressed as frequency (percentage). The independent two-sample t-test was used for between-group comparisons. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Statistical significance was indicated for two-sided p-values <0.05. All statistical analyses were performed using SPSS version 19.0 (SPSS Inc., Chicago, IL, USA).