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Which Biomarker to Stratify Prognosis in Pulmonary Arterial Hypertension?

Rui Placido

Joao Marques

Susana Martins

Claudia Jorge

Carina Calisto

Susana Goncalves

Sonia Ribeiro

Ana Almeida

A. Nunes Diogo

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Conference: 2012 International PHA Conference and Scientific Sessions

Release Date: 06.22.2012

Presentation Type: Abstracts

Rui Plácido, João S. Marques, Susana R. Martins, Cláudia Jorge, Carina Calisto, Susana Gonçalves, Sónia Ribeiro, Ana G. Almeida, A. Nunes Diogo.

Centro Hospitalar Lisboa Norte, Hospital de Santa Maria – Lisbon, Portugal

PURPOSE: Pulmonary arterial hypertension (PAH) is a rare, deadly condition. Although risk stratification is extremely importantant to assess prognosis and guide therapy there is lack of evidence concerning the role of novel biomarkers. We sought to comparatively investigate the predictive power of several biomarkers assessed at baseline in predicting death or hospital admission at 12 months.

METHODSProspective cohort study in 28 patients with clinical and hemodynamic diagnosis of PAH followed up in a universitary hospital PAH clinic. Primary end-point was defined as death or hospital admission due to PAH related clinical worsening. Study protocol included baseline clinical assessment, 6 minute walking test, conventional and speckle tracking echocardiography and analytical evaluation including several conventional biomarkers (uric acid, NT-proBNP, troponin) and novel biomarkers (CTproET-1, MR-proANP, MR-proADM and copeptin). Patients were prospectively followed-up at the clinica t least once every three months. Results are presented as median (interquartil range) or number (%).

RESULTS: Most patients were female (n=21, 75%) aged 61.0 (43.0-69.75) years. Twenty patients (71%) were in WHO class I or II. Fourteen patients (50%) were on endothelin antagonists, 12 (43%) on phosphodiesterase inhibitors and 4 (14%) on prostacyclins. Distance walked at baseline was 352.5 (253.0-  419.0 m. TAPSE was 18.5 (14.8-23.0)mm and RV fractional area change was 33.0 (22.1-42.3)%. During the 12 months follow-up there were two deaths and six hospital admissions (29% event rate at 12 months).

The group of patients who had events had significantly higher baseline levels of CT-proET-1(<0.01), Copeptin (0.05), MR-proANP (p<0.01), NT-proBNP (p<0.01) and troponin I (p=0.02). Right atrial diameter was significantly higher in patients that developed events. Time-dependent analysis was carried out using Kaplan Meier survival curves with log rank analysis. There was significantly less event-free survival in patients in the third tertile of CT-proET-1 (p<0.01), Copeptin (p<0.01), NT-proBNP (0.02) and creatinine (p=0.02). In multivariable Cox regression CT-pro-ET-1 (OR=10.1; p<0.01) was the only independent predictor of events at 12 moths among studied biomarkers. This fact remained true even after adjustment for baseline pharmacological treatment.

CONCLUSION: CT-proET-1 provided independent prognostic information regarding time to clinical event (death or hospital admission) at 12 months in patients with PAH. Importantly, we provide first evidence that CT-proET-1 may be superior to commonly used biomarkers for predicting prognosis.