Abstract

Background: Natriuretic peptides and their second messenger, cyclic guanosine monophosphate (cGMP), play a critical role in the pathogenesis of cardiovascular diseases by inhibiting the renin-aldosterone system, cardiac hypertrophy, and fibrosis. Recently developed chemiluminescent enzyme immunoassays for proBNP have enabled the estimation of mature BNP (emBNP) by calculating the difference between total BNP and proBNP. Research Questions: The role of cGMP in left ventricular remodeling after acute myocardial infarction (AMI) remains poorly understood. Aims: We aimed to investigate the relationship between the natriuretic peptide-cGMP cascade and left ventricular reverse remodeling (RR) in patients with anterior AMI. Methods: In a prospective 67 patients experiencing their first anterior AMI, plasma BNP fractions and cGMP levels were measured at immediate primary percutaneous coronary intervention (PPCI), 3 days, and 3 months post-AMI. Change in left ventricular end-systolic index (delta-LVESVI) was calculated as the difference between median 10 months and day 10 using cardiac magnetic resonance imaging. Patients were divided into RR and non-RR groups based on regression analysis to compute residuals representing the differences between each individual’s observed delta-LVESVI and delta-LVESVI adjusted by plasma pro-BNP concentration at immediate PPCI because of an inverse correlation between delta-LVESVI and plasma pro-BNP concentration at immediate PPCI (r=0.243, p=0.047). RR group (n=33) demonstrated below-median residual delta-LVESVI, while non-RR group (n=34) had above-median residual. Results: RR group exhibited significantly higher freedom from major adverse cerebral and cardiovascular events (MACCE) during a median of 8.1-year (Interquartile range: 6.7–8.8) follow-up (P=0.024) (Figure A) . Multivariable analysis identified logarithmic plasma pro-BNP, and emBNP at day 3 post-AMI, and plasma cGMP levels at immediate PPCI and day 3 post-AMI, as independent predictors of RR (P<0.05) even after adjusting age, male, hypertension, and infarct size. (Figure B-D) . Conclusion: Early-phase activation of the natriuretic peptides-cGMP cascade may play a protective role in left ventricular remodeling in patients with anterior AMI.