NT-proBNP in the Early Convalescent Phase after High-Risk Myocardial Infarction Is Associated with Adverse Cardiovascular Outcomes: the PARADISE-MI Trial.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with heart failure (HF) hospitalizations and death when measured during a myocardial infarction (MI). However, NT-proBNP concentrations change following the initial ischemic insult and less is known about the prognostic importance of NT-proBNP in the early convalescent phase.

Methods: PARADISE-MI randomized 5661 patients with MI complicated by LVEF ≤40% and/or pulmonary congestion to sacubitril/valsartan or ramipril. Patients with available week 2 NT-proBNP concentrations and without incident HF between randomization and week 2 (n=1062) were analyzed. Associations of week 2 NT-proBNP with subsequent clinical outcomes were evaluated in landmark analyses using Cox models adjusted for clinical characteristics including LVEF, baseline NT-proBNP and atrial fibrillation.

Results: Median 2-week NT-proBNP was 1391 [676 - 2507] ng/L. Patients in the highest NT-proBNP quartile (≥2507 ng/L) were older, had lower LVEF and eGFR, higher Killip class and more atrial fibrillation. Higher NT-proBNP concentrations were independently associated with greater risk of CV death or incident HF (adjusted HR [aHR] 1.65 per doubling of NT-proBNP; 95% CI, 1.31-2.09), HF hospitalization (aHR 1.87; 95% CI, 1.38-2.54), recurrent MI (aHR 1.46; 95% CI, 1.09-1.95) and all-cause death (aHR 1.85; 95% CI, 1.35-2.53).

Conclusions: Patients with elevated NT-proBNP concentrations approximately two weeks after a high-risk MI are at heightened risk of incident HF, recurrent coronary events and death, independent of baseline NT-proBNP concentrations and clinical characteristics. Elevations in NT-proBNP concentrations in the early convalescent phase may assist in risk stratification and identification of patients in need for more advanced preventive treatment approaches.

Lay summary: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of ventricular wall stress and in the acute phase of a myocardial infarction (MI) is strongly associated with adverse cardiovascular outcomes. NT-proBNP concentrations change dynamically after MI but they are not routinely remeasured during follow-up. In a contemporary post-MI population enrolled in the PARADISE-MI trial, NT-proBNP measured approximately two weeks following MI was independently associated with heightened risk of death, incident heart failure and recurrent MI. NT-proBNP concentrations in the early convalescent phase may help risk stratify patients following MI and identify those in need for closer follow-up and more aggressive therapies.