Background: Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described. Objective: To investigate whether plasma concentrations of cTnI and CRP are associated with severity of MMVD, and investigate potential associations of dog characteristics on cTnI and CRP concentrations. Animals: Eighty-one client-owned dogs with MMVD of varying severity. Methods: Dogs were prospectively recruited for the study. Dogs were classified according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA. Results: Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0.008–0.029] ng/mL, P= .0011) and severe (0.043 [0.031–0.087] ng/mL, P < .0001) MMVD, compared with healthy dogs (0.001 [0.001–0.004] ng/mL). Dogs with severe MMVD also had higher cTnI concentrations than dogs with mild (0.003 [0.001–0.024] ng/mL, P < .0001) and moderate (P= .0019) MMVD. There were significant associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration. Conclusions and Clinical Importance: Analysis of cTnI concentration has potential to increase knowledge of overall cardiac remodeling in dogs with MMVD. However, effect of age on cTnI needs consideration when assessing cTnI.
Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans—mitral valve prolapse—is 1–5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 ( Pgenome = 4.0× 10 −5 ) and a 1.68 Mb region on CFA14 ( Pgenome = 7.9× 10 −4 ) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.
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.