The Predictive Value of Clinical, Radiographic, Echocardiographic Variables and Cardiac Biomarkers for Assessing Risk of the Onset of Heart Failure or Cardiac Death in Dogs with Preclinical Myxomatous Mitral Valve Disease Enrolled in the DELAY Study

Objectives: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NTproBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). Animals: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio >1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter >1.7 were included. Methods: Prospective, randomized, multicenter, single-blinded, placebo -controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. Results: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 rmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. Conclusions: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death. 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).