Galectin-3, GDF-15, and sST2 for the assessment of disease severity and therapy response in patients suffering from inoperable chronic thromboembolic pulmonary hypertension.

PURPOSE: This study examined sST2, GDF-15, and galectin-3 as indicators of disease severity and therapy response in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 57 inoperable CTEPH patients who underwent balloon pulmonary angioplasty and 25 controls without cardiovascular disease. Biomarker levels were examined in relation to advanced hemodynamic impairment [tertile with worst right atrial pressure (RAP) and cardiac index], hemodynamic therapy response [normalized hemodynamics (meanPAP ≤25 mmHg, PVR ≤3 WU and RAP ≤6 mmHg) or a reduction of meanPAP ≥25%; PVR ≥ 35%, RAP ≥25%]. RESULTS: GDF-15 [820 (556-1315) pg/ml vs. 370 (314-516) pg/ml; p < 0.001] and sST2 [53.7 (45.3-74.1) ng/ml vs. 48.7 (35.5-57.0) ng/ml; p = 0.02] were higher in CTEPH patients than in controls. At baseline, a GDF-15 level ≥1443 pg/ml (AUC 0.88; OR 31.4) and a sST2 level ≥65 ng/ml (AUC 0.80; OR 10.9) were associated with advanced hemodynamic impairment. At follow-up GDF-15 ≤ 958 pg/ml (AUC = 0.74, OR 18) identified patients with optimal hemodynamic therapy response and ≤760 pg/ml (AUC = 0.79, OR 14). CONCLUSION: GDF-15 and sST2 levels are higher in CTEPH and identified patients with advanced hemodynamic impairment. Further, decreased GDF-15 levels at follow-up were associated with hemodynamic therapy response. The diagnostic strength was not superior to NT-proBNP.

Development of renal function during staged balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA), for chronic thromboembolic pulmonary hypertension, improves pulmonary and systemic hemodynamics. The kidney might benefit from this effect. However, staged BPA therapy comes along with repetitive administration of contrast agent. This study examined the overall effect of BPA therapy on renal function. This study included consecutive patients who underwent BPA treatment and completed a 6-month follow-up between March 2014 and March 2017. Biomarker-based evaluation of renal function was performed at baseline, consecutively prior to and after each BPA and at 6-month follow-up. The 51 patients underwent an average of 5 (±2) BPA sessions. In this course, patients received 133 (±48; 21-300) mL of contrast agent per session and 691 (±24; 240-1410) mL during the whole sequence. Acute kidney injury occurred after 6 (2.3%) procedures. The creatinine [80.1 (IQR 67.8-96.8) µmol/L vs. 77.4 (IQR 66.9-91.5) µmol/L, p = .02] and urea level [13.7 (IQR10.7-16.6) mmol/L vs. 12.5 (IQR 10.0-15.5) mmol/L, p = .02] decreased from baseline to the 6-month follow-up. The estimated glomerular filtration rate (eGFR) [79 (IQR 59-94) mL/min/m2 vs. 79.6 (IQR 67.1-95.0) mL/min/m2, p = .11] did not change. The Chronic kidney disease (CKD) stages at baseline were: G1:15; G2:23; G3a:10; G3b:2; G4:1; G5:0. Among patients with a CKD-stage ≥2, analysis revealed an increase of eGFR, decrease of creatinine and urea from baseline to 6-month follow-up. Among those patients, the baseline-CKD-stage improved in 14 (41.2%) patients. BPA therapy improves pulmonary and systemic hemodynamics, with positive effects on renal function. Repetitive administration of contrast agent seems not to be harmful regarding renal function.

Dynamics of high-sensitivity cardiac troponin T during therapy with balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

AIMS: Balloon pulmonary angioplasty (BPA) is an interventional treatment modality for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Therapy monitoring, based on non-invasive biomarkers, is a clinical challenge. This post-hoc study aimed to assess dynamics of high-sensitivity cardiac troponin T (hs-cTnT) as a marker for myocardial damage and its relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as a marker for cardiac wall stress. METHODS AND RESULTS: This study included 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between 3/2014 and 3/2017. Biomarker measurement was performed consecutively prior to each BPA and at 6-MFU. In total, the 51 patients underwent an average of 5 BPA procedures. The 6-month survival rate was 96.1%. The baseline (BL) meanPAP (39.5±12.1mmHg) and PVR (515.8±219.2dyn×sec×cm-5) decreased significantly within the 6-MFU (meanPAP: 32.6±12.6mmHg, P<0.001; PVR: 396.9±182.6dyn×sec×cm-5, P<0.001). At BL, the median hs-cTnT level was 11 (IQR 6-16) ng/L and the median NT-proBNP level was 820 (IQR 153-1872) ng/L. The levels of both biomarkers decreased steadily after every BPA, showing the first significant difference after the first procedure. Within the 6-MFU, hs-cTnT levels (7 [IQR 5-12] ng/L; P<0.001) and NT-proBNP levels (159 [IQR 84-464] ng/l; P<0.001) continued to decrease. The hs-cTnT levels correlated with the PVR (rrs = 0.42; p = 0.005), the meanPAP (rrs = 0.32; p = 0.029) and the NT-proBNP (rrs = 0.51; p<0.001) levels at BL. CONCLUSION: Non-invasive biomarker measurement provides valuable evidence for the decreasing impairment of myocardial function and structure during BPA therapy. Changes in hs-cTNT levels are suggestive for a reduction in ongoing myocardial damage.