Elevated Outpatient C-Reactive Protein Independently Predicts All-Cause Mortality in LVAD Recipients

Y. Brailovsky, A. Javaid, G. M. Mondellini, L. Braghieri, J. S. Murphy, N. Uriel, G. T. Sayer, V. K. Topkara, K. Takeda, Y. Naka, R. T. Demmer, M. Yuzefpolskaya, P. C. Colombo

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Abstract

PURPOSE: LVAD therapy is associated with persistent inflammation and residual congestion. C-Reactive Protein (CRP), erythrocyte sedimentation rate (ESR) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) are established biomarkers of inflammation and congestion. We sought to investigate the association between these biomarkers and mortality in LVAD patients who survived to their first outpatient visit. METHODS: Serum CRP, ESR and NT-proBNP were prospectively measured at outpatient visits in consecutive LVAD pts. Biomarker levels were averaged over the duration of follow up. Receiver Operator Characteristic (ROC) curves were constructed to identify the optimal biomarkers cut off points to predict all-cause mortality. Multivariable Cox proportional hazard model was built to assess the association between CRP and mortality after adjusting for age, gender, BMI, diabetes, INTERMACS profile, NT-proBNP and presence of driveline infection. RESULTS: 228 patients (105 HeartMate II and 105 HeartMate 3, 18 other devices) were studied. On average, there were 9.4±7.0, 11.0±7.6, and 9.5±6.6 measurements per pt for CRP, ESR and NT-proBNP, respectively, over a median follow-up of 564 (IQR 266-895) days. 28 pts died at a median time of 482 (IQR 185-966) days. In the entire cohort, the median levels of CRP, ESR and NT-proBNP were 14.3 (IQR 6.2-30.3)mg/L, 37.4 (IQR 25.0-52.9)mm/hr, and 1135 (IQR 663-2348)pgl/mL. The ROC curves identified the following cut offs to predict mortality: CRP 17.2 (AUC 0.72, p<0.001), ESR 55.2 (AUC 0.61, p=0.046) and NT-proBNP 2664 (AUC 0.61, p=0.044) (Fig 1). Multivariable Cox proportional hazard model demonstrated that CRP >17.2 mg/L was an independent predictor of all-cause mortality (HR 8.35. 95% CI 2.94- 23.7, p<0.001). CONCLUSION: Elevated outpatient CRP is an independent predictor of all-cause mortality in LVAD recipients.

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