Myxomatous Mitral Valve Disease Dogs Research Articles

Quantification of respiratory sinus arrhythmia in control dogs and in dogs with various severity classes of myxomatous mitral valve disease

IntroductionLoss of respiratory sinus arrhythmia (RSA) is a negative prognostic factor in dogs with myxomatous mitral valve disease (MMVD). The aim of this study was to calculate the percentage (%) of RSA in healthy dogs and dogs in various MMVD classes. AnimalsControl and MMVD dogs were prospectively included in the study. Materials and methodsRespiratory sinus arrhythmia was calculated from a dual channel electrocardiography and breathing curve recording using the peak-to-trough method, in percent of the average heart rate. ResultsOne hundred and forty-nine dogs were studied, including 24 control and 125 MMVD dogs of different severity classes. An overall %RSA decrease was documented with increasing disease severity up to the Ca class along with a relative %RSA increase in the Cc class. The %RSA magnitude differed between B2 and Ca (P<0.001), and between Ca and Cc (P = 0.001) groups, respectively. The %RSA showed a medium negative correlation with the La:Ao ratio (r2 = −0.568, P<0.001) and with the E-wave velocity (r2 = −0.561, P<0.001). DiscussionsA decrease in %RSA was shown with increased disease severity up to acute congestive heart failure (CHF). Dogs receiving cardiac therapy leading to stabilized CHF might restore their ability to exhibit RSA, often revealing a higher %RSA compared to those in acute CHF. Study limitationsLow number of respiratory cycles for analysis. Therapy effect not evaluated. ConclusionsThe findings of this study can serve as the basis for future risk stratification and carry the potential of proving an additional clinical marker for diagnostic and therapeutic decisions making when managing MMVD dogs.

Iron parameters analysis in dogs with myxomatous mitral valve disease.

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms. Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group. Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD.

Comparison of St. Thomas II Cardioplegia and Modified Del Nido Cardioplegia in Dogs Undergoing Mitral Valve Surgery.

Myocardial protection has become an essential adjunctive procedure in veterinary cardiac surgery. Del Nido cardioplegia is a good alternative to the traditional St. Thomas II (ST) cardioplegia in open heart surgery in humans. This study aims to compare intra- and postoperative results between ST cardioplegia and modified del Nido (mDN) cardioplegia in mitral valve surgery in dogs with myxomatous mitral valve disease (MMVD). This retrospective study was conducted using clinical records of 16 MMVD dogs that underwent either ST or mDN cardioplegia. We measured cardiopulmonary bypass (CPB) time, aortic cross-clamp (ACC) time, total operation time, the number of cardioplegia doses, total amount of cardioplegia, required defibrillations, in-hospital mortality and pre- and one-month postoperative echocardiographic variables. CPB (159.4 ± 16.1 vs. 210.1 ± 34.0 min), ACC (101.4 ± 7.0 vs. 136.0 ± 24.8 min) and total operation time (262.3 ± 13.1 vs. 327.0 ± 45.4 min) were significantly shorter in the mDN group (p < 0.05). The number of cardioplegia doses (3.25 ± 0.4 vs. 6.25 ± 1.2) and total amount of cardioplegia (161.3 ± 51.5 vs. 405.0 ± 185.9 mL) in the mDN group were also significantly smaller than the ST group (p < 0.05). No difference was observed in the requirement of defibrillation, in-hospital mortality and pre- and postoperative echocardiographic variables. The utilization of mDN cardioplegia was associated with shorter operative time in mitral valve surgery in dogs.

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. 74 dogs (control, n = 12; MMVD, n = 62) were included. Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Proteomic analysis of the serum in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease: the preliminary study.

Pulmonary hypertension (PH) is a common complication in dogs with myxomatous mitral valve disease (MMVD), characterized by elevated blood pressure in pulmonary artery. Echocardiography is a reliable technique for PH diagnosis in veterinary medicine. However, it is limited to use as an early detection method. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has found extensive application in the discovery of serum protein biomarkers for various diseases. The objective of this study was to identify serum proteins in healthy control dogs and MMVD dogs both with and without PH using LC-MS/MS. In this research, a total of 81 small-breed dogs participated, and they were categorized into three groups: the control (n = 28), MMVD (n = 24) and MMVD+PH (n = 29) groups. Serum samples were collected and analyzed by LC-MS/MS. Differentially expressed proteins were identified, and the upregulated and downregulated proteins in MMVD+PH group including Myomesin 1 (MYOM1) and Histone deacetylase 7 (HDAC7), Pleckstrin homology domain containing M3 (PLEKHM3), Diacylglycerol lipase alpha (DAGLA) and Tubulin tyrosine ligase like 6 (TTLL6) were selected as proteins of interest in MMVD dogs with PH. Different types of proteins have been identified in healthy dogs and MMVD dogs with and without PH. Additional studies are needed to investigate the potential of these proteins as biomarkers for PH in dogs with MMVD.

Differentially expressed platelet activation-related genes in dogs with stage B2 myxomatous mitral valve disease

BackgroundPeripheral blood carries a reservoir of mRNAs that regulate cardiac structure and function potential. Although it is well recognized that the typical symptoms of Myxomatous Mitral Valve Disease (MMVD) stage B2 are long-standing hemodynamic disorder and cardiac structure remodeling caused by mitral regurgitation, the transcriptomic alterations in blood from such dogs are not understood.ResultsIn the present study, comparative high-throughput transcriptomic profiling of blood was performed from normal control (NC) and naturally-occurring MMVD stage B2 (MMVD) dogs. Using Weighted Gene Co-expression Network Analyses (WGCNA), Gene Ontology (GO), and Kyoto Encyclopedia of Gene and Genomes (KEGG), we identified that the turquoise module was the most highly correlated with echocardiographic features and found 64 differentially expressed genes (DEGs) that were significantly enriched in platelet activation related pathways. Therefore, from the turquoise module, we selected five DEGs (MDM2, ROCK1, RIPK1, SNAP23, and ARHGAP35) that, according to real-time qPCR, exhibited significant enrichment in platelet activation related pathways for validation. The results showed that the blood transcriptional abundance of MDM2, ROCK1, RIPK1, and SNAP23 differed significantly (P < 0.01) between NC and MMVD dogs. On the other hand, Correlation Analysis revealed that MDM2, ROCK1, RIPK1, and SNAP23 genes negatively regulated the heart structure parameters, and followed the same trend as observed in WGCNA.ConclusionWe screened four platelet activation related genes, MDM2, ROCK1, RIPK1, and SNAP23, which may be considered as the candidate biomarkers for the diagnosis of MMVD stage B2. These findings provided new insights into MMVD pathogenesis.

Investigation of red blood cell and platelet indices in adult dogs suffered from myxomatous mitral valve disease with and without pulmonary hypertension.

Pulmonary hypertension (PH) is a common complication of cardiopulmonary disease. In dogs, PH commonly occurs secondary to myxomatous mitral valve disease (MMVD). Red blood cell and platelet indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), mean platelet volume (MPV) and platelet distribution width (PDW), have previously been found to be indicators for predicting and prognosing PH in humans. Therefore, this study aimed to investigate whether these indices are associated with MMVD and/or PH in dogs. Two hundred and forty-six dogs were retrospectively recruited for the study and classified into 4 groups: normal (n = 49), MMVD (n =102), PH (n =17), MMVD+PH (n =78). A sub-analysis was performed in dogs with MMVD without evidence of PH according to stage B1 (n =20), stage B2 (n =15), stage C (n =67). The data are expressed as median (interquartile range). No significant differences (p < 0.05) were found in MCV, RDW and MPV among all groups (normal, MMVD, PH and MMVD+PH). However, decreases in MCH and MCHC were found in MMVD [22.40 (20.90-23.50) pg and 35.25 (33.08-36.90) g/dL], MMVD+PH [22.25 (20.85-23.98) pg and 35.65 (33.30-37.33) g/dL] and PH groups [21.20 (20.60-22.20) pg and 33.80 (32.75-35.70) g/dL] compared to the normal dogs [24.29 (23.55-24.90) pg and 38.20 (37.50-39.05) g/dL] (p < 0.001). Decreases in PDW were found in dogs in the MMVD+PH [15.10 (14.98-15.30) %] groups compared to dogs in the normal group [15.30 (15.10-15.50) %] (p = 0.004). Sub-analysis of MMVD dogs without PH showed a decrease in MCH in dogs with stage B2 MMVD [21.00 (20.50-22.90) pg] and stage C MMVD [22.40 (20.90-23.20) pg] compared to normal dogs [24.29 (23.55-24.90) pg] (p < 0.001). MCHC of dogs with stage B1 [36.55 (33.53-37.78) g/dL] (p = 0.004), B2 [32.90 (32.00-35.00) g/dL] (p < 0.001) and C MMVD [35.30 (33.30-36.80) g/dL] (p < 0.001) were lower than those of normal dogs [38.20 (37.50-39.05) g/dL]. PDW in the stage C MMVD group [15.10 (15.00-15.30) %] was reduced compared to the normal group [15.30 (15.10-15.50) %] (p = 0.042) and the stage B1 MMVD group [15.35 (15.23-15.68) %] (p = 0.002). MCH, MCHC and PDW were negatively correlated with the left atrial and left ventricular size. Decreases in MCH and MCHC are related to MMVD, precapillary PH and postcapillary PH while PDW are associated with MMVD severity but not with the presence of PH.

Correlation between the Leaflet-Annulus Index and Echocardiographic Indices in Maltese Dogs with Myxomatous Mitral Valve Disease.

Myxomatous mitral valve disease (MMVD) is the most common chronic heart valve disease, leading to left-sided cardiomegaly in dogs. The leaflet-annulus index (LAI) was originally used in humans as a predictor of mitral regurgitation (MR) after mitral valve repair surgery. This index represents the quantity and severity of MR since it is affected by annular dilation. Recently, LAI was adapted to veterinary medicine, and its usefulness as an indicator of annular dilation on 2D transthoracic echocardiography in MMVD dogs was suggested. For this study, 135 Maltese dogs were selected and divided into groups of control, B1, and B2, according to the American College of Veterinary Internal Medicine consensus statement. The following data were collected: radiographic indices including the vertebral heart score and vertebral left atrial size, echocardiographic indices including the left-atrium-to-aortic-root ratio (LA:Ao), left ventricular internal diameter at diastole, normalized for body weight, and anteroposterior length and LAI measured on right parasternal long-axis view. The results showed a significant difference in LAI between each group, becoming smaller as the disease progressed. Also, there was a significant correlation between LAI and each index, showing the strongest correlation with LA:Ao. LAI could be helpful as a new indicator used for the determination of severity and prognosis in Maltese dogs with MMVD.

Neutrophil-to-lymphocyte ratio is increased in dogs with acute congestive heart failure secondary to myxomatous mitral valve disease compared to both dogs with heart murmurs and healthy controls.

To retrospectively evaluate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as a biomarker for severity and short-term outcomes of congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) in dogs. 47 dogs with CHF secondary to MMVD, 47 dogs with presumptive preclinical MMVD, and 47 control dogs. Medical record data (signalment, physical examination findings, medical treatments instituted, American College of Veterinary Internal Medicine MMVD stage, length of hospitalization, outcome, and hospital re-presentation due to CHF) from March 2012 through March 2022 for each dog were collected. Statistical analyses were performed with Mann-Whitney, Spearman correlation, and Fisher exact tests. NLR (but not PLR) was significantly higher in dogs with CHF secondary to MMVD (6.41) compared to presumptive preclinical MMVD dogs (4.66; P < .001) and control dogs (3.95; P < .001). Dogs with higher NLR and PLR received significantly higher cumulative dosages of loop-diuretic therapy during hospitalization (ρ = 0.3, P = .04; and ρ = 0.4, P = .02, respectively). There was a positive association between NLR and duration of oxygen supplementation within the CHF group (ρ = 0.4; P = .01). The increased diuretic dose and time receiving oxygen supplementation may represent increased disease severity for which NLR (and to a lesser extent PLR) may serve as a readily available marker. The data presented provide information regarding some of the systemic inflammatory changes seen in CHF secondary to MMVD in dogs. Future research should include prospective, longitudinal studies to provide insight into the long-term prognostic value of NLR and PLR in dogs with CHF.

Severity of myxomatous mitral valve disease in dogs may be predicted using neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratio.

To investigate the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in dogs with myxomatous mitral valve disease (MMVD). 106 dogs with MMVD and 22 healthy dogs were included in the study. CBC data were obtained retrospectively, and NLR, MLR, and PLR were compared between dogs with MMVD and healthy dogs. The ratios were also analyzed according to MMVD severity. NLR and MLR were significantly higher in dogs with MMVD C and D (NLR of 4.99 [3.69-7.27]; MLR of 0.56 [0.36-0.74]) than in healthy dogs (NLR: 3.05 [1.82-3.37], P < .001; MLR: 0.21 [0.14-0.32], P < .001), MMVD stage B1 (NLR: 3.15 [2.15-3.86], P < .001; MLR: 0.26 [0.20-0.36], P < .001), and MMVD stage B2 dogs (NLR: 3.22 [2.45-3.85], P < .001; MLR: 0.30 [0.19-0.37], P < .001). The area under the receiver operating characteristic curves of the NLR and MLR to distinguish dogs with MMVD C and D from those with MMVD B were 0.84 and 0.89, respectively. The optimal cutoff value for NLR was 4.296 (sensitivity, 68%; specificity, 83.95%), and the MLR value was 0.322 (sensitivity, 96%; specificity, 66.67%). NLR and MLR were significantly decreased after treatment in dogs with congestive heart failure (CHF). NLR and MLR can be used as adjunctive indicators of CHF in dogs.

Perivascular inflammatory cells and their association with pulmonary arterial remodelling in dogs with pulmonary hypertension due to myxomatous mitral valve disease.

Pulmonary hypertension (PH), an increase in pulmonary arterial pressure (PAP), may occur in dogs affected with myxomatous mitral valve disease (MMVD). Recent studies suggest that an accumulation of perivascular inflammatory cells may be involved with medial thickening which is a sign of the pulmonary artery remodelling in PH. The aim of this study was to characterise perivascular inflammatory cells in the surrounding pulmonary arteries of dogs with PH due to MMVD compared to MMVD dogs and healthy control dogs. Nineteen lung samples were collected from cadavers of small-breed dogs (control n = 5; MMVD n = 7; MMVD + PH n = 7). Toluidine blue stain and multiple IHC targeting α-SMA, vWF, CD20, CD68 and CD3 was performed to examine intimal and medial thickening, assess muscularisation of the small pulmonary arteries and characterise perivascular leucocytes. Medial thickening without intimal thickening of pulmonary arteries and muscularisation of normally non-muscularised small pulmonary arteries was observed in the MMVD and MMVD + PH groups compared with the control group. The perivascular numbers of B lymphocytes, T lymphocytes and macrophages was significantly increased in the MMVD + PH group compared with the MMVD and control groups. In contrast, the perivascular number of mast cells was significantly higher in the MMVD group compared with the MMVD + PH and control groups. This study suggested that pulmonary artery remodelling as medial thickening and muscularisation of the normally non-muscular small pulmonary arteries is accompanied by the accumulation of perivascular inflammatory cells.

TGF-β-induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease.

PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double-immunofluorescence examined expression of PI3K and TGF-β1 in canine valves. Valve interstitial cells (VICs) from healthy or MMVD dogs were isolated and characterized. Healthy quiescent VICs (qVICs) were treated with TGF-β1 and SC-79 to induce activated myofibroblast phenotypes (aVICs). Diseased valve-derived aVICs were treated with PI3K antagonists and expression of RPS6KB1 (encoding p70 S6K) was modulated using siRNA and gene overexpression. SA-β-gal and TUNEL staining were used to identify cell senescence and apoptosis, and qPCR and ELISA to examine for senescence-associated secretory phenotype. Protein immunoblotting was used to examine expression of phosphorylated and total proteins. TGF-β1 and PI3K are highly expressed in mitral valve tissues. Activation of PI3K/AKT/mTOR and increased expression of TGF-β are found in aVICs. TGF-β transitions qVICs to aVICs by upregulation of PI3K/AKT/mTOR. Antagonism of PI3K/AKT/mTOR reverses aVIC myofibroblast transition by inhibiting senescence and promoting autophagy. Upregulation of mTOR/S6K induces transformation of senescent aVICs, with reduced capacity for apoptosis and autophagy. Selective knockdown of p70 S6K reverses cell transition by attenuating cell senescence, inhibiting apoptosis and improving autophagy. TGF-β-induced PI3K/AKT/mTOR signalling contributes to MMVD pathogenesis and plays crucial roles in the regulation of myofibroblast differentiation, apoptosis, autophagy and senescence in MMVD.

Prognostic value of left atrial stiffness estimated using echocardiography in dogs with myxomatous mitral valve disease

IntroductionNo studies have investigated the prognostic value of left atrial stiffness (LASt) estimated using echocardiography in dogs with myxomatous mitral valve disease (MMVD). AnimalsSeventy-two dogs had MMVD and 46 dogs were healthy dogs. Materials and MethodsClinical retrospective cohort study. The survival information of MMVD dogs that underwent echocardiographic examination was obtained. The peak velocities of early diastolic transmitral flow (E) and mitral annular motion as determined by pulsed wave Doppler (E′) were determined. The left atrial reservoir strain (εS) was determined by two-dimensional speckle tracking echocardiography of the left atrium. The LASt was estimated by the formula: E/E′/εS. The 95% prediction interval of LASt was computed from the data of the healthy dogs. ResultsSeventeen dogs having MMVD died of cardiac-related causes with 55 MMVD dogs censored. The MMVD dogs with LASt > its 95% upper prediction limit (LASt > 0.56; n = 26; median survival time, 484 days; 95% confidence interval, 283 days-indeterminable) had shorter survival times (P<0.001) than those with LASt ≤ its 95% upper prediction limit (LASt ≤ 0.56; n = 46; median survival time, >1112 days; 95% confidence interval, indeterminable). Multivariable Cox's proportional hazard analysis demonstrated that the ratio of the left atrial dimension to the aortic annulus dimension and LASt were independent predictors of cardiac-related death among conventional echocardiographic indices, εS and LASt in MMVD dogs. ConclusionsIn dogs with MMVD, increased LASt estimated using echocardiography is an independent predictor of cardiac-related death, and LASt can be more useful for prognostication than εS.

Effects of Coenzyme Q10 Supplementation on Oxidative Stress Markers, Inflammatory Markers, Lymphocyte Subpopulations, and Clinical Status in Dogs with Myxomatous Mitral Valve Disease.

Scarce data exist on the effects of coenzyme Q10 (CoQ10) supplementation in dogs with myxomatous mitral valve disease (MMVD). The purpose of this study was to investigate the effect of CoQ10 supplementation on oxidative stress markers (glutathione peroxidase, F2-isoprostanes), markers of inflammation (tumor necrosis factor-α, TNF soluble receptor II, leucocytes, and their subtypes), lymphocyte subpopulations (T helper and cytotoxic T lymphocytes, including activated T lymphocytes, and B lymphocytes), and echocardiographic and clinical parameters in dogs with MMVD. In this randomized, controlled, double-blind, longitudinal study, 43 MMVD dogs in stages ACVIM (American College of Veterinary Internal Medicine classification) B2 and ACVIM C and D (congestive heart failure (CHF)) received water-soluble coenzyme Q10 (100 mg twice daily) or placebo for 3 months, and 12 non-supplemented healthy dogs served as controls. All parameters were measured before and after supplementation in MMVD dogs and once in healthy dogs. CoQ10 supplementation had a positive impact on neutrophil percentage, lymphocyte percentage, and lymphocyte concentration in our cohort of dogs with CHF (ACVIM C and D). Conclusion: CoQ10 as an oral supplement may have benefits in terms of decreasing inflammation in dogs with MMVD and CHF.

Evaluation of endothelial cell-specific molecule-1 as a biomarker of glycocalyx damage in canine myxomatous mitral valve disease

BackgroundEndothelial cell-specific molecule-1 (ESM-1) has emerged as a potential biomarker for cardiovascular disease in humans. Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs, and we hypothesized that MMVD causes chronic inflammation that increases susceptibility to endothelial glycocalyx (eGCX) damage. In this study, we measured the concentration of ESM-1 in a group of dogs with MMVD and evaluated factors affecting eGCX damage.ResultsSixty-four dogs (control, n = 6; MMVD, n = 58) were enrolled in this study. There was no significant difference in serum ESM-1 concentrations among the MMVD stages. The serum ESM-1 concentration was significantly higher in the death group than in the alive group in MMVD dogs. (p = 0.006). In five dogs with MMVD, serum ESM-1 concentrations tended to decrease when the cardiac drug (pimobendan, furosemide, and digoxin) dose was increased.ConclusionsIn cases where MMVD progressed to decompensated heart failure with clinical symptoms and resulted in death, the concentration of serum ESM-1 increased significantly. Therefore, ESM-1 could be utilized as a new potential negative prognostic factor in patients with MMVD.

Pro-Inflammatory and Immunological Profile of Dogs with Myxomatous Mitral Valve Disease.

Simple SummaryMyxomatous mitral valve disease (MMVD) is the most commonly acquired cardiac disease in dogs and is responsible for congestive heart failure. In this research, some inflammatory, immunological, and echocardiographic parameters were evaluated in dogs affected by MMVD in order to assess the involvement of additional pathophysiological mechanisms during the disease. The main results revealed that inflammation parameters increased according to the severity of the disease and suggested that inflammatory activation may play an important role in cardiac remodeling associated with the progressive volumetric overload in MMVD. Also, a relative increase in Treg cells was detected, suggesting that they could represent a regulatory mechanism for limiting the inflammatory immune response.Myxomatous mitral valve disease (MMVD) is a very frequently acquired cardiac disease in dog breeds and is responsible for congestive heart failure (CHF). The involvement of the immune system and pro-inflammatory cytokines in dogs with CHF due to mitral valve disease has not yet been extensively investigated. Here, we investigate the role of pro-inflammatory cytokines and the dysfunction of the immune system in dogs with different stages of severity through the blood assessment of CD4+FoxP3+regulatory T cells (Treg) cells, leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 pro-inflammatory cytokines, and immunological and echocardiographic parameters. A total of 36 cardiopathic dogs, 14 females and 22 males, with MMVD were included. Mean age and body weight (BW) at the time of enrollment were 10.7 ± 2.77 years and 10.9 ± 6.69 kg, respectively. For the comparison of the pro-inflammatory and immunological parameters, two groups of healthy dogs were also established. Control group 1 consisted of young animals (n. 11; 6 females and 5 males), whose age and mean weight were 4.1 ± 0.82 years and 13.8 ± 4.30 kg, respectively. Control group 2 consisted of elderly dogs (n. 12; 6 females and 6 males), whose age and BW were 9.6 ± 0.98 years and 14.8 ± 6.15 kg, respectively. Of particular interest, an increase in Treg cells was observed in the cohort of MMVD dogs, as compared to the healthy dogs, as Treg cells are involved in the maintenance of peripheral tolerance, and they are involved in etiopathogenetic and pathophysiological mechanisms in the dog. On the other hand, TNF-α, IL-1β, and IL-6 significantly increased according to the severity of the disease in MMVD dogs. Furthermore, the positive correlation between IL-6 and the left ventricle diastolic volume suggests that inflammatory activation may be involved in cardiac remodeling associated with the progressive volumetric overload in MMVD.

Influence of concurrent lower respiratory tract disease on point-of-care lung ultrasound in small-breed dogs with myxomatous mitral valve disease.

BackgroundSmall‐breed dogs commonly have concurrent myxomatous mitral valve disease (MMVD) and lower respiratory tract disease (LRTD).HypothesisSmall‐breed dogs with preclinical MMVD and concurrent LRTD have more B‐lines on point‐of‐care lung ultrasound (POC‐LUS) compared to dogs without concurrent LRTD and are prone to misdiagnose as cardiogenic pulmonary edema (CPE).AnimalsA total of 114 small‐breed dogs with preclinical MMVD.MethodsA prospective study was conducted, in which POC‐LUS was obtained and the number of B‐lines was calculated by a single clinician using the Veterinary Bedside Lung Ultrasound Examination protocol. The presence/absence of LRTD was assessed by clinicians blinded to the POC‐LUS results.ResultsFifty and 64 dogs were in ACVIM stage B1 and B2, respectively. The presence of LRTD was prevalent in 74.6% (85/114) of small‐breed dogs with preclinical MMVD. When a previously reported criterion for CPE diagnosis (≥2 sites with >3 B‐lines/site) was applied, false‐positive results were observed in 15.8% (18/114) of dogs with preclinical MMVD. The summated number of B‐lines (3 vs. 1, P = .003), as well as the false‐positive rate (20% vs 3%, P = .04), were significantly higher in dogs with LRTD compared with dogs without LRTD. Multivariable logistic regression showed the presence of abnormalities other than B‐line on POC‐LUS (eg, thickened pleura or consolidation) could predict false‐positive results (odds ratio = 3.75, 95% confidence intervals 1.12‐12.54; P = .03) after adjustment for other clinical and echocardiographic factors.Conclusions and Clinical ImportanceConcurrent LRTD and abnormalities other than B‐lines should be considered in the interpretation of POC‐LUS in MMVD dogs.

Effect of sampling time on urinary electrolytes following oral furosemide administration in dogs with myxomatous mitral valve disease

Introduction/ObjectivesUrine chemistry has received growing attention to estimate the diuretic response in dogs with cardiac disease.The aim of the study was to evaluate the impact of time elapsed between the oral furosemide administration and sample collection on urine chemistry in dogs with myxomatous mitral valve disease (MMVD) receiving diuretic therapy in American College of Veterinary Internal Medicine (ACVIM) stage C. Materials and methodsSeventy-three dogs with MMVD ACVIM stage C and 106 healthy dogs were prospectively included. Dogs with MMVD were divided, based on the time of sampling, in morning group (MMVD-MG) of one to 6 h and an evening group (MMVD-EG) over 6 h from oral furosemide administration. Analogously, healthy dogs sampled between 9 a.m. and 1 p.m. and between 2 and 7 p.m. were divided in a morning group (H-MG) and an evening group (H-EG), respectively. Urine chemistry, including fractional excretion of electrolytes, was evaluated and compared among groups. ResultsHigher excretion of sodium and chloride and higher urine sodium to urine potassium ratio (uNa+:uK+) were detected in MMVD-MG than MMVD-EG (P = 0.021, P = 0.038, and P = 0.016, respectively). Natriuresis, chloriuresis, and uNa+:uK+ were higher in MMVD-MG than H-MG, while no differences were found in the comparison between H-MG and H-EG and between MMVD-EG and H-EG. ConclusionsUrinary electrolyte excretion is significantly increased within 6 h from furosemide administration in MMVD ACVIM stage C dogs. Time of sampling from furosemide administration significantly affects urine chemistry in MMVD dogs and should be considered in clinical practice and the research field.

Changes in renin-angiotensin-aldosterone system during cardiac remodeling after mitral valvuloplasty in dogs.

BackgroundInformation regarding changes in renin‐angiotensin‐aldosterone system (RAAS) during cardiac remodeling after mitral valvuloplasty (MVP) in dogs remains lacking.Hypothesis/ObjectivesTo assess the longitudinal effects of MVP on circulating RAAS activity.AnimalsEight client‐owned dogs receiving MVP for myxomatous mitral valve disease (MMVD).MethodsThis is a cohort study. Plasma renin activity (PRA), angiotensin II (AT2), aldosterone (PAC), blood urea nitrogen (BUN), and creatinine concentrations, were measured in these dogs before (baseline) and at 3 consecutive monthly follow‐ups (Post‐1M, Post‐2M, Post‐3M). Echocardiography was concomitantly used to assess the process of cardiac recovery after MVP.ResultsThe echocardiography revealed a significant decrease in LVIDDN, LA/Ao, FS, E velocity, E/A, E′ sep, S′ lat, E′ lat, and A′ lat after MVP compared with baseline (P < .05). There was a significant reduction in the PRA (2.45, 3.05, 2.74 vs 8.8 ng/mL/h; P = .002), AT2 (466, 315, 235 vs 1200 pg/mL; P = .009), and PAC (39.88, 47, 54.62 vs 179.5 pg/mL; P = .01), respectively at Post‐1M, Post‐2M, Post‐3M compared to the baseline. Additionally, BUN and creatinine concentrations decreased from Post‐1M. The RAAS variables showed significant, weak to moderate, relationship with selected echocardiographic variables.Conclusions and Clinical ImportanceMitral valvuloplasty contributes to decreased RAAS activity in MMVD dogs, which paralleled the process of cardiac reverse remodeling up to Post‐3M. This information facilitates formulating strategies to optimize clinical outcomes for dogs after MVP.

Prognostic value of selected one-, two- and three-dimensional and Doppler echocardiographic methods to assess severity in dogs with myxomatous mitral valve disease

IntroductionAlthough challenging, predicting outcomes in dogs with myxomatous mitral valve disease (MMVD) is of importance to owners and veterinarians. Our aim was to compare the prognostic value of selected one-, two-, and three-dimensional and Doppler echocardiographic methods to predict cardiac-related and all-cause mortality in MMVD dogs. We hypothesize that three-dimensional methods would better predict prognosis than one- and two-dimensional methods. AnimalsOne-hundred thirty-eight privately-owned dogs with MMVD. Materials and methodsCox proportional Hazard analyses and Kaplan–Meier curves were used to investigate the predictive value of 14 variables; left atrial (LA) volume indexed to body weight (BW) measured by real-time three-dimensional echocardiography (RT3DE) and calculated using Simpson's modified method of discs (SMOD) and the area-length method; LA diameter in short-axis and long-axis to aortic in short-axis ratio, effective regurgitant orifice area indexed to body surface area measured in RT3DE en face view and calculated using four-chamber (4Ch) and two-chamber views alone or in combination; percentage increase in left ventricular end-diastolic and systolic internal diameters; fractional shortening; E wave velocity; regurgitant jet area/LA area. ResultsAll 14 variables were significantly predictive of cardiac-related mortality, and 11 were predictive of all-cause mortality. The prognosis was best predicted by LA volume/BW estimated by SMOD or RT3DE, consistently showing the highest predictive value in all analyses. ConclusionsLeft atrial volume calculated by SMOD showed a similar predictive value compared to RT3DE. Performing SMOD from apical 4Ch images should be considered an alternative to RT3DE for echocardiographic examinations where prognostication of disease outcome is sought.