Risk stratification guided by NT-proBNP after cardiac rehabilitation in patients with ST-segment elevation myocardial infarction

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) is the reference biomarker for risk stratification of heart failure clinical events. However, in the context of patients with ST-segment elevation myocardial infarction (STEMI), its use is much less established. Although studies in the acute phase have linked higher NT-proBNP levels with worse clinical outcomes, current guidelines scarcely include specific recommendations regarding the routine analysis of this parameter following a myocardial infarction. The analysis of NT-proBNP could provide objective, easily accessible, and cost-effective information for risk stratification in STEMI patients after Cardiac Rehabilitation. Purpose We aim to evaluate the prognostic role of NT-proBNP determination in a homogeneous series of STEMI patients treated with primary angioplasty, evaluated with imaging techniques, and who have completed a phase 2 Cardiac Rehabilitation program. Methods The prognostic significance of NT-proBNP was tested during and after ambulatory phase 2 Cardiac Rehabilitation Program (median, 45 days post-STEMI) after treatment optimization. The study was conducted in two phases: an exploratory cohort of 105 STEMI patients (the researchers were blinded to NT-proBNP values) and validated in the following 276 patients. Baseline and cardiac imaging variables including cardiovascular magnetic resonance (CMR) parameters were recorded. The primary endpoint was the occurrence of a first major adverse cardiac event (MACE: cardiac death, myocardial infarction, or re-admission for heart failure). Results In the exploratory group (n=105), patients who experienced MACE had higher NT-proBNP levels. An NT-proBNP level >400pg/mL emerged as the best cutoff and was independently associated with a higher risk of experiencing a first MACE (37% vs. 17%; HR: 6.8 [1.5–30.3], p=0.01). In the study group (n=246), during a 203-week median follow-up, 88 (32%) first MACEs were detected. NT-proBNP >400pg/mL (n=168, 61%) was associated with a higher MACE rate (46% vs. 10%, HR: 4.6 [2.3-8.9], p<0.001) and, separately, with more cardiac deaths, myocardial infarctions, and re-admissions for heart failure (p<0.05 for all comparisons). In multivariate analysis, NT-proBNP >400pg/mL was an independent predictor of MACE after adjustment for diabetes mellitus, GRACE risk score, and left ventricular ejection fraction (LVEF) derived from CMR (HR 4.6 [2.3-8.9], p<0.001). NT-proBNP improved the multivariate model for MACE prediction (area under the curve 0.81 vs. 0.72, p <0.001). Analyzing all measurements performed during follow-up (n=1018), the risk of transition to MACE was higher in case of NT-proBNP >400pg/mL (14% vs. 3%, p <0.001). Conclusions NT-proBNP emerges as a potent, accessible and cost-effective tool for risk stratification in STEMI patients during and after Phase 2 Cardiac Rehabilitation Program.Association of NT-proBNP with MACE