Old markers, new approach to assessment of risk in heart failure

Heart transplantation (HTx) is still the optimal treatment for refractory heart failure (HF). However, there is great disproportion between the number of donors and potential recipients. Several parameters are used in patient evaluation before HTx, but the qualification process still requires improvement. High-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) possess high prognostic value for patients with advanced HF.

To assess the prognostic significance of NT-proBNP and hsCRP separately, as well as in combination, in a group of patients with advanced HF, considered for HTx.

Registry — 632 patients referred for HTx in Poland (2003–2007). Following proper treatment correction and routine clinical evaluation (i.e. mean New York Heart Association [NYHA] classification 3.2 ± 0.6, heart rate 77 ± 15 bpm, systolic/diastolic blood pressure [SBP/DBP] 103/67 ± 15/11 mm Hg, left ventricular ejection fraction [LVEF] 22 ± 8%, serum Na+ 136 ± 4 mmol/L, NT-proBNP 3942 ± 5637 pg/mL, hsCRP 9 ± 22 mg/L levels, HFSS according to Aaronson 8 ± 1, etc.) patients were qualified for HTx. Based on ROC analysis (cut-off points for NT-proBNP 2435 pg/mL and hsCRP 2.4 mg/L) subjects were stratified into four subgroups: (1) non-elevated hsCRP (–)/NT-proBNP (–) (n = 179); (2) non-elevated hsCRP (–)/ /elevated NT-proBNP (+) (n = 92); (3) elevated hsCRP (+)/non-elevated NT-proBNP (–) (n = 159); and (4) elevated hsCRP (+)/ /NT-proBNP (+) (n = 202). The end point was defined as death/urgent HTx. The mean follow-up period was 601 days.

In univariate regression analysis we confirmed that classical risk factors were independent predictors of end point: NYHA (HR = 2.311; p < 0.0001), heart rate (HR = 1.016; p = 0.0009), SBP (HR = 0.984; p = 0.0111), LVEF (HR = 0.951; p < 0.0001), serum Na+ (HR = 0.901; p < 0.0001), NT-proBNP (HR = 1.004; p = 0.0159), and hsCRP (HR = 1.010; p = 0.0002); HFSS (HR = 0.557; p < 0.0001). Frequency-of-events analysis revealed that patients in the hsCRP (–)/ /NT-proBNP (–) subgroup presented with the best prognosis (13% of patients reached end point) followed by the hsCRP (–)/ /NT-proBNP (+) subgroup, in which 24% of patients reached end point (Kaplan-Meier c2 = 8.5319; p = 0.0035) and the hsCRP (+)/NT-proBNP (+) subgroup (c2 = 42.0413; p < 0.0001), which was associated with the worst prognosis (39% of patients reached end point).

The classical risk factors: NYHA class, heart rate, SBP, LVEF, HFSS, serum Na+, NT-proBNP, and hsCRP concentrations, proved to be valuable in the assessment of risk in advanced HF patients. However, concomitant evaluation of old markers: hsCRP and NT-proBNP, may become a good prognostic tool for identification of highest-risk patients among all referred for HTx. Such a new approach to risk stratification before HTx seems promising but requires further investigation.