Cardiac Troponin I Is Associated with Severity of Myxomatous Mitral Valve Disease, Age, and C-Reactive Protein in Dogs

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.     

Diagnostic Value of Selected Echocardiographic Variables to Identify Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease

Background

Pulmonary hypertension (PH) is commonly associated with myxomatous mitral valve disease (MMVD). Because dogs with PH present without measureable tricuspid regurgitation (TR), it would be useful to investigate echocardiographic variables that can identify PH.

Aim

To investigate associations between estimated systolic TR pressure gradient (TRPG) and dog characteristics and selected echocardiographic variables.

Animals

156 privately owned dogs.

Materials and Methods

Prospective observational study comparing the estimations of TRPG with dog characteristics and selected echocardiographic variables in dogs with MMVD and measureable TR.

Results

Tricuspid regurgitation pressure gradient was significantly (P < .05) associated with body weight corrected right (RVIDDn) and left (LVIDDn) ventricular end‐diastolic and systolic (LVIDSn) internal diameters, pulmonary arterial (PA) acceleration to deceleration time ratio (AT/DT), heart rate, left atrial to aortic root ratio (LA/Ao), and the presence of congestive heart failure. Four variables remained significant in the multiple regression analysis with TRPG as a dependent variable: modeled as linear variables LA/Ao (P < .0001) and RVIDDn (P = .041), modeled as second order polynomial variables: AT/DT (P = .0039) and LVIDDn (P < .0001) The adjusted R ² ‐value for the final model was 0.45 and receiver operating characteristic curve analysis suggested the model''s performance to predict PH, defined as 36, 45, and 55 mmHg as fair (area under the curve [AUC] = 0.80), good (AUC = 0.86), and excellent (AUC = 0.92), respectively.

Conclusion and Clinical Importance

In dogs with MMVD, the presence of PH might be suspected with the combination of decreased PA AT/DT, increased RVIDDn and LA/Ao, and a small or great LVIDDn.     

Effect of Pimobendan on Echocardiographic Values in Dogs with Asymptomatic Mitral Valve Disease

Background: Pimobendan (PIMO) is a novel inodilator that has shown promising results in the treatment of advanced mitral valve disease (MVD), but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring MVD.
Hypothesis: The addition of pimobendan to treatment decreases the regurgitant fraction (RF) in dogs with asymptomatic MVD.
Animals: Twenty-four client-owned dogs affected by International Small Animal Cardiac Health Council class Ib MVD.
Methods: Prospective, blinded, and controlled clinical trial. Dogs were assigned to a PIMO treatment group (n = 19) (0.2–0.3 mg/kg q12h) or a control group (n = 5). Echocardiographic evaluations were performed over a 6-month period.
Results: The addition of PIMO to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period ( P = .85). There was a significant increase in the ejection fraction of the PIMO treated dogs at 30 days (80.8 ± 1.42 versus 69.0 ± 2.76, corrected P = .0064), and a decrease in systolic left ventricular diameter (corrected P = .011) within the PIMO group compared with baseline. However, this improvement in systolic function was not sustained over the 6-month trial period.
Conclusion and Clinical Importance: This study did not identify beneficial long-term changes in the severity of mitral regurgitation after addition of PIMO to angiotensin converting enzyme inhibitor treatment of dogs with asymptomatic MVD.     

Biopterin Status in Dogs with Myxomatous Mitral Valve Disease is Associated with Disease Severity and Cardiovascular Risk Factors

Background

Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium‐derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress.

Objective

To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD.

Animals

Eighty‐four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]).

Methods

Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high‐performance liquid chromatography with fluorescence detection.

Results

Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations.

Conclusions and Clinical Importance

Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.     

Prevalence and Prognostic Importance of Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease

Background

Pulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated.

Hypothesis/objectives

The presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH.

Animals

Two hundred and twelve client‐owned dogs.

Methods

Case review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long‐term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3 m/s.

Results

Two hundred and twelve were identified. Eighty‐three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P < .0001). One hundred and five (49.5%) dogs died during the observation period. Median survival time for the entire study population was 567 days (95% CI 512–743). Stage C (P = .003), the presence of PH (P = .009), left atrial to aortic root ratio (LA/Ao) >1.7 (P = .0002), normalized left‐ventricular end‐diastolic diameter (LVEDn) >1.73 (P = .048), and tricuspid regurgitation pressure gradient (TRPG) >55 mmHg (P = .009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55 mmHg (HR 1.8 95% CI 1–2.9; P = .05) and LA/Ao > 1.7 (HR 2 95% CI 1.2–3.4; P = .01) remained significant predictors of worse outcome in the multivariate analysis.

Conclusions and Clinical Importance

In dogs with MMVD, moderate to severe PH worsens outcome.     

Evaluation of Pimobendan and N-Terminal Probrain Natriuretic Peptide in the Treatment of Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease in Dogs

Background: Pimobendan is a positive inotrope and vasodilator that may be useful in the treatment of pulmonary hypertension (PHT) secondary to degenerative mitral valve disease.
Hypothesis: Pimobendan decreases the severity of PHT measured echocardiographically and improves quality-of-life scores. Changes in N-terminal probrain natriuretic peptide (NT-proBNP) concentrations will reflect improvement in severity of PHT.
Animals: Ten client-owned dogs with peak tricuspid regurgitant flow velocity (TRFV) ≥3.5 m/s.
Methods: Prospective short-term, double-blinded, crossover design, with a long-term, open-label component. Short term, dogs were randomly allocated to receive either placebo or pimobendan (0.18–0.3 mg/kg PO q12 h) for 14 days. After a 1-week washout, they received the alternative treatment for 14 days, followed by pimobendan open-label for 8 weeks.
Results: Short-term comparison: peak TRFV decreased in all dogs on pimobendan compared with placebo from a median of 4.40 (range, 3.2–5.6) to 3.75 (range, 2.4–4.8) m/s ( P < .0001). NT-proBNP concentration decreased after treatment with pimobendan from a median of 2,143 (range, 450–3,981) to 1,329 (range, 123–2,411) pmol/L ( P = .0009). All dogs improved their quality-of-life score ( P = .006). In the long-term comparisons, peak TRFV decreased in all dogs from a median of 4.28 (range, 3.5–5.7) to 3.52 (range, 2.4–5.0) m/s ( P < .0001). No significant changes in NT-proBNP or quality-of-life scores were detected.
Conclusions and Clinical Importance: Pimobendan lowered severity of measurable PHT, improved quality-of-life scores, and decreased NT-proBNP concentrations short-term. Long term, only the reduction in TRFV was maintained.     

Pathologic Manifestations on Surgical Biopsy and Their Correlation with Clinical Indices in Dogs with Degenerative Mitral Valve Disease

Background

Evaluation of myocardial function is clinically challenging in dogs with degenerative mitral valve disease (DMVD). Although myocardial dysfunction is caused by pathologic degeneration, histopathologic progression is poorly understood.

Objectives

To characterize myocardial and pulmonary pathologic changes according to severity in dogs with naturally occurring DMVD, and to investigate whether or not pathologic degeneration is reflected by traditional clinical indices.

Animals

One hundred and seventeen dogs with naturally occurring DMVD.

Methods

Prospective observational study. Biopsied left atrium (LA), left ventricle (LV), and lung were evaluated histologically, and an attempt was made to correlate pathologic findings with clinical indices.

Results

Severe myocardial changes were observed in all International Small Animal Cardiac Health Council classes. In the lung, heart failure cell levels were significantly increased in class III patients (P < .0001). In a paired comparison, the LA showed significantly more severe degeneration than the LV, including myocardial fatty replacement, immune cell infiltration, and interstitial fibrosis (P < .0001). In contrast, myocardial cells were more hypertrophied in the LV than in the LA (P < .0001). Left ventricular end‐diastolic dimension (LVEDd) was associated with fatty replacement (P = .033, R ² = 0.584) and myocardial vacuolization (P = .003, R ² = 0.588) in the LA.

Conclusions and Clinical Importance

In DMVD, although severe pathologic changes may be evident even in early stages, there may be pathologic discrepancy between the LA and the LV. Myocardial degeneration may be reflected by clinical indices such as LVEDd and EF.     

Noninvasive Clinical Assessment of Systolic Torsional Motions by Two‐Dimensional Speckle‐Tracking Echocardiography in Dogs with Myxomatous Mitral Valve Disease

Background

Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two‐dimensional speckle‐tracking echocardiography (2D‐STE) in dogs with myxomatous mitral valve disease (MMVD) has not been reported.

Hypothesis

Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods.

Animals

Sixty‐seven client‐owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight‐ and age‐matched healthy dogs.

Methods

Dogs were examined for myocardial deformations by 2D‐STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate.

Results

Peak systolic torsion was higher in class II than in class I (P < .001) dogs. Peak systolic torsion was lower in class III than in class II (P = .001) dogs and controls (P = .003).

Conclusions and Clinical Importance

Torsional deformations assessed by 2D‐STE differed among clinical classes of MMVD. Myocardial torsional deformations by 2D‐STE may provide more detailed assessment of contractile function in dogs with MMVD.     

Longitudinal Electrocardiographic Evaluation of Dogs with Degenerative Mitral Valve Disease

Background

Increased heart rate (HR) and decreased heart rate variability (HRV) are evident in some dogs with degenerative mitral valve disease (DMVD).

Objectives

Evaluation of the factors influencing HR and HRV (assessed by the vasovagal tonus index; VVTI) and their change over time in dogs with DMVD.

Animals

Client‐owned dogs (n = 257) with DMVD recruited from first opinion practice.

Methods

Prospective longitudinal follow‐up at six‐monthly intervals of dogs with DMVD. Dogs followed up for at least 18 months (n = 102) were grouped according to their outcome as dogs dying/euthanized because of cardiac disease (n = 28; Group 1), noncardiac disease (n = 40; Group 2) and dogs alive (n = 34; Group 3). HR and VVTI were measured on 1‐minute ECG recordings. Repeated measures linear models were constructed to investigate the factors that influence HR and VVTI and their changes over time.

Results

Heart rate and VVTI were affected by disease severity and were different in Cavaliers compared to other breeds. Group 1 and Group 2 dogs underwent an increase in HR and decrease in VVTI, evident at least 18 months before death. Group 1 had a further decrease in VVTI followed by an increase in HR approximately 1 year and 6 months before death, respectively.

Conclusions and Clinical Importance

Dogs with DMVD have an increase in HR and decrease in HRV over a year before death, with greater changes in those dogs dying/euthanized because of cardiac disease. Both HR and VVTI can potentially be regarded as biomarkers for all‐cause mortality.