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Background Cardiovascular disease is associated with endothelial dysfunction in humans and studies of plasma biomarkers suggest that dogs with myxomatous mitral valve disease ( MMVD) might also have endothelial dysfunction. Hypothesis That progression of mitral regurgitation ( MR) is associated with development of endothelial dysfunction. Animals Forty-three Cavalier King Charles Spaniels ( CKCS) with MR of varying severity. Methods Privately owned CKCS were prospectively recruited and divided in 4 groups: (1) 12 CKCS with minimal MR; (2) 9 CKCS with mild MR; (3) 11 CKCS with moderate-severe MR; and (4) 11 CKCS with moderate-severe MR and clinical signs compatible with heart failure. Dogs underwent blood sampling, echocardiography, blood pressure ( BP) recordings, and flow-mediated vasodilation ( FMD) measurements. The effect of progressive MR on FMD was determined by multivariate analyses. Results Flow-mediated vasodilation decreased with progression of MR. Group 4 (4.79 ± 3.22%) had significantly lower FMD than groups 1 (10.40 ± 4.58%) and 2 (10.14 ± 3.67%) ( P < .005) and group 3 (6.79 ± 3.98%) had a significantly lower FMD than group 1 ( P = .03). Increasing left ventricular end-diastolic diameter ( P = .0004, R2 = 0.27) and the combination of age ( P = .01) and body weight ( P = .002) (R2 = 0.31) were significantly associated with reduced FMD. FMD did not correlate with sex, BP, or plasma markers. Conclusions and Clinical Importance Reduced FMD indicates that increased disease severity in CKCS with MMVD is associated with development of endothelial dysfunction which might be a future therapeutic and/or diagnostic target. [ABSTRACT FROM AUTHOR]

Background Autonomic modulation of heart rhythm is thought to influence the pathophysiology of myxomatous mitral valve disease ( MMVD). Hypotheses (1) Holter-derived variables reflecting autonomic modulation of heart rhythm change with MMVD severity in Cavalier King Charles Spaniels ( CKCS); (2) Holter-derived variables can identify MMVD severity in CKCS; and (3) Holter-derived variables in CKCS in congestive heart failure ( CHF) secondary to MMVD differ from those in dogs of other breeds in CHF. Animals Ninety privately owned dogs: 70 CKCS with variable MMVD severity and 20 non- CKCS in CHF secondary to MMVD. Methods Dogs were prospectively recruited and divided into 5 MMVD severity groups based on history, breed, and physical and echocardiographic examination findings. Holter-derived variables included heart rate variability ( HRV), heart rate ( HR), and arrhythmia evaluated from 24-hour Holter recordings. Results In CKCS, 18 of 26 HRV (all P < .0002) and 3 of 9 arrhythmia (all P < .0004) variables decreased with increasing MMVD, whereas minimum and mean HR (all P < .0001) increased with increasing MMVD severity. An arrhythmia variable representing sinus arrhythmia ('premature normals') ( P < .0001) and the HRV variable triangular index ( TI) ( P < .0001) could distinguish CKCS with moderate or severe mitral regurgitation from CKCS in CHF in specific intervals. Among dogs in CHF, Holter-derived variables did not differ among breeds. Conclusions and Clinical Importance In CKCS, Holter-derived variables changed with MMVD severity. 'Premature normals' and TI showed diagnostic potential. Breed differences were not seen among dogs in CHF secondary to MMVD. [ABSTRACT FROM AUTHOR]