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.     

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.     

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.     

Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with Myxomatous Mitral Valve Disease

Background

Right ventricular (RV) dysfunction independently predicts outcomes in human myxomatous mitral valve disease (MMVD). There is limited information regarding RV systolic function in dogs with MMVD.

Hypothesis

Right ventricular systolic function differs among stages of disease, decreasing in decompensated MMVD.

Animals

Thirty‐sixclient‐owned dogs with MMVD not receiving oral cardiovascular medications.

Methods

Prospective clinical study. Dogs were categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven echocardiographic indices of RV systolic function were measured. Groups were compared by 1‐way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac remodeling falling outside previously established reference intervals were compared using Fisher's exact test. Intra‐ and interobserver measurement variability was calculated for each RV function index.

Results

The indices TAPSE (P = 0.029), RV St_L (P = 0.012), and RV StR_L (P = 0.041) were significantly different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs (P = 0.027). Measurement variability of TAPSE, RV S', and RV St_G was clinically acceptable.

Conclusions and Clinical Importance

Right ventricular systolic function differs between stages of MMVD, increasing in stage B2, and declining in stage C. The prognostic importance of RV function indices, particularly TAPSE, might be worth evaluating in dogs with MMVD.     

Longitudinal Analysis of Quality of Life,Clinical, Radiographic,Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background

Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD ) and cardiomegaly have not been described.

Objectives

To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF ) or cardiac‐related death (CRD ) in dogs with MMVD and cardiomegaly. To determine whether pimobendan‐treated dogs differ from dogs receiving placebo at onset of CHF .

Animals

Three hundred and fifty‐four dogs with MMVD and cardiomegaly.

Materials and Methods

Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4–0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart‐size variables in both groups were measured and compared at different time points (day 35 and onset of CHF ) and over the study duration. Relationships between short‐term changes in echocardiographic variables and time to CHF or CRD were explored.

Results

At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN ?0.06 (IQR : ?0.15 to +0.02), P  < 0.0001, and LA :Ao ?0.08 (IQR : ?0.23 to +0.03), P  < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD . Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P  = 0.0003. Hazard ratio for a 0.1 increase in ΔLA :Ao was 1.14, P  = 0.0002. At onset of CHF , groups were similar.

Conclusions and Clinical Importance

Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF , dogs treated with pimobendan were indistinguishable from those receiving placebo.

     

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.     

Usefulness of Conventional and Tissue Doppler Echocardiography to Predict Congestive Heart Failure in Dogs with Myxomatous Mitral Valve Disease

Background

Systolic and diastolic functions have been evaluated to predict outcome in congestive heart failure (CHF). Recently, tissue Doppler imaging (TDI) has become useful for the estimation of myocardial function in cardiac diseases of humans and animals.

Objective

This study was designed to assess whether myocardial function as assessed by TDI is associated with the occurrence of CHF in dogs with myxomatous mitral valve disease (MMVD) and whether additional information is gained over conventional Doppler variables.

Animals

Forty‐one privately owned dogs (15 healthy dogs and 26 dogs with MMVD) were included. Dogs with MMVD were divided into non‐CHF (n = 10) and CHF groups (n = 16).

Methods

Conventional echocardiographic examinations were performed. In addition, TDI‐derived variables, including radial and longitudinal velocities, strain, and strain rate were assessed.

Results

Several (12 of 47, 26%) conventional and tissue Doppler echocardiography variables were significant predictors of CHF in a univariate analysis (P < .05). However, TDI‐derived E/E _{m sept} was the only load‐independent significant predictor of CHF (P < .05) after multivariate logistic regression analysis. The E/E _{m sept} cut‐off value of >18.7 had a sensitivity of 56% and specificity of 90% in predicting CHF in dogs with MMVD.

Conclusions and Clinical Importance

The combination of TDI of the mitral annulus and mitral inflow velocity provided better estimates of diastolic dysfunction in dogs with MMVD and CHF. Additional study is warranted to assess TDI‐derived E/E _{m sept}, an index of diastolic function that could contribute to the management of dogs with MMVD and CHF.     

Change of Vertebral Left Atrial Size in Dogs With Preclinical Myxomatous Mitral Valve Disease Prior to the Onset of Congestive Heart Failure

Introduction/objectivesIt has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility.Animals, materials and methodsForty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared.ResultsAt the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83–155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not.ConclusionsVLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.     

Cardiac Troponin‐I Concentration,Myocardial Arteriosclerosis,and Fibrosis in Dogs with Congestive Heart Failure because of Myxomatous Mitral Valve Disease

Background

Few previous studies have investigated the association between biomarkers and cardiac disease findings in dogs with naturally occurring myxomatous mitral valve disease (MMVD).

Aim

To investigate if histopathological changes at necropsy could be reflected by in vivo circulating concentrations of cTnI and aldosterone, and renin activity, in dogs with naturally occurring congestive heart failure because of MMVD.

Animals

Fifty privately owned dogs with MMVD and heart failure.

Methods

Longitudinal Study. Dogs were prospectively recruited and examined by clinical and echocardiographical examination twice yearly until time of death. Blood was stored for batched analysis of concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a standardized necropsy protocol.

Results

cTnI were associated with echocardiographic left ventricular end‐diastolic dimension (P < .0001) and proximal isovolumetric surface area radius (P < .004). Furthermore, in vivo cTnI concentrations reflected postmortem findings of global myocardial fibrosis (P < .001), fibrosis in the papillary muscles (P < .001), and degree of arterial luminal narrowing (P < .001) Aldosterone or renin activity did not reflect any of the cardiac disease variables investigated.

Conclusion and clinical importance

Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases.