Prospective pilot study on the predictive significance of plasma miR-30b-5p through the study of echocardiographic modifications in Cavalier King Charles Spaniels affected by different stages of myxomatous mitral valve disease: The PRIME study

Abstract

Specific microRNAs expressions may accurately characterize different stages of canine myxomatous mitral valve disease. This preliminary pilot study aimed to (1) describe the clinical and echocardiographic parameters of Cavalier King Charles Spaniels affected by myxomatous mitral valve disease at different American College of Veterinary Internal Medicine (ACVIM) stages (B1, B2 and C) and healthy control group (ACVIM A), comparing the parameters collected during the first examination (T0) and the end of the follow-up (T1); (2) assess the association between the values of echocardiographic parameters at T1 and the expression profile of miR-30b-5p at T0. Thirty-five Cavalier King Charles Spaniels (median age 4.29 years and median weight 9 Kg) in different ACVIM stages were included (7 A, 19 B1, 6 B2 and 3 C). Inverse probability weighting analysis was performed to estimate the association of the exposure variable (miR-30b-5p) with the outcome variables (clinical and echocardiographic variables). Time was included as variable. The results pointed out that high levels of plasma miR-30b-5p corresponded to lower values of left ventricular end-diastolic diameter normalized for body weight, end-diastolic and end-systolic volumes indexed for body weight, and left atrium-to aortic root ratio. Hence, higher miR-30b-5p expressions were associated with milder forms of mitral valve disease in our study population. In contrast, the results obtained for the intensity of heart murmur, the mitral regurgitation severity, and the Mitral INsufficiency Echocardiographic score) were not statistically significant. A relationship between high abundance of miR-30b-5p and myxomatous mitral valve disease that appear echocardiographically more stable over time has been demonstrated. In conclusion, Cavalier King Charles Spaniels affected by myxomatous mitral valve disease that at the first cardiologic evaluation showed an upregulation of miR-30b-5p are expected to experience lesser variations on their echocardiographic examination between T0 and T1.

Fig 1. Marginal effect of plasma miR-30b-5p expression on echocardiographic variables at T0 and T1.

Black line: T0. Red line: T1. A) Marginal effect of miR-30b-5p on LVIDdN. B) Marginal effect of miR-30b-5p on ESVI: The interaction between the two parameters is high since T0 and T1 lines are poorly parallel. C) Marginal effect of miR-30b-5p on EDVI. D) Marginal effect of miR-30b-5p on LA/Ao.

Fig 2. Marginal effect of plasma miR-30b-5p expression on ordinal variables at T0 and T1.

Black line: T0. Red line: T1. On the y-axis, the probability of the class with the lower value is reported. A) Marginal effect of miR-30b-5p on the presence/intensity of a heart murmur. B) Marginal effect of miR-30b-5p on the mitral regurgitant jet size. C) Marginal effect of miR-30b-5p on the MINE score.