Potential prognostic indicators in dogs with advanced heart failure secondary to myxomatous mitral valve disease.

BACKGROUND: Advanced heart failure (AHF) secondary to myxomatous mitral valve disease (MMVD) in dogs has unclear predictive variables and survival time. METHODS: This retrospective study included 38 dogs with AHF and 38 with stable congestive heart failure (CHF), both due to MMVD. Predictive variables for AHF were analysed, and survival times were calculated using logistic regression and the Kaplan-Meier method. RESULTS: Left atrium to aortic root ratio, normalised left ventricular dimension at the end-diastole and end-systole, isovolumic relaxation time (IVRT) and early transmitral inflow velocity to IVRT ratio were associated with AHF progression. The median survival times were significantly longer in the stable group than in the AHF group. After AHF diagnosis, the median survival times for all-cause and cardiogenic mortality were 194 and 354 days, respectively. LIMITATIONS: This was a single-centre retrospective observational study. The study population was small, with breed bias (overrepresentation of Maltese dogs). Additionally, the treatment plans depended on clinical experience. CONCLUSIONS: AHF in dogs with CHF secondary to MMVD is linked to left heart chamber enlargement and increased left ventricular dimensions, significantly reducing survival time to around six months post-diagnosis. Early recognition and appropriate management may improve outcomes, highlighting the importance of advanced treatment strategies.

How accurate are NT-proBNP, ANP, and cTnI levels in diagnosing dogs with myxomatous mitral valve disease?

Background: Myxomatous mitral valve disease (MMVD) is prevalent in dogs. Specialized diagnostics (radiography and echocardiography) may be unavailable in some veterinary settings. Cardiac biomarkers offer potential alternatives. Aim: This study evaluated the diagnostic value of N-terminal fragments of pro-brain natriuretic peptides (NT-proBNPs), atrial natriuretic peptides (ANPs), and cardiac troponin I (cTnI) levels in dogs with MMVD. Methods: 69 dogs with MMVD (asymptomatic and symptomatic) and 19 healthy controls were assessed. Biomarker levels were measured using commercial kit rapid tests. Results: Our results showed that the median NT-proBNP level in the symptomatic group was higher than those in the asymptomatic (p < 0.001) and control (p < 0.001) groups. Moreover, the median NT-proBNP level in the asymptomatic group was higher than that in the control group (p < 0.001). The cTnI level in the control group was lower than those in the asymptomatic (p = 0.039) and symptomatic (p = 0.001) groups. No statistically significant difference in the cTnI level was noted between the asymptomatic and symptomatic groups. The best cutoff value of the NT-proBNP level to differentiate the normal controls from dogs with MMVD with or without congestive heart failure was > 505.65 pmol/l [sensitivity, 76.8%; specificity, 89.5%; and area under the curve (AUC), 0.862]. The suggested cutoff value of the NT-proBNP level to differentiate symptomatic MMVD from asymptomatic MMVD was >787.65 pmol/l (sensitivity, 78.38%; specificity, 72.55%; and AUC, 0.792). Conclusion: NT-proBNP and cTnI may serve as point-of-care tests for dyspneic dogs, aiding MMVD assessment where specialized diagnostics are limited.

Neutrophil-to-lymphocyte ratio and red blood cell distribution width to platelet ratio and their relationships with inflammatory and antioxidant status in dogs with different stages of heart failure due to myxomatous mitral valve disease.

We aimed to evaluate the red blood cell distribution width-to-platelet ratio (RDW/PLT) with other complete blood cell count (CBC) indices and their correlations with serum proinflammatory cytokines, acute phase proteins (APPs), and antioxidant biomarkers in dogs at different stages of heart failure (HF). A total of 29 dogs were divided into four groups according to the ACVIM Consensus Statement: stage-A (healthy/controls, n = 8), stage-B2 (n = 6), stage-C (n = 10), and stage-D (n = 5). Seventeen CBC indices were calculated and correlated with the measurements of inflammatory, APPs, and antioxidant biomarkers, as well as selected echocardiographic variables in all dogs. At stage-C, CBC indices were evaluated 14 days after the treatment. Statistically significant changes were observed only for RDW/PLT and neutrophil-to-lymphocyte ratio (NLR) between groups. NLR increased, but RDW/PLT deceased in dogs with HF, compared to controls (P < 0.05). There were no statistically differences between pre- and post-treatment CBC indices. There were significantly positive and negative correlations between the CBC indices, serum parameters and selected echocardiographic variables in dogs with HF(P < 0.05). ROC analysis showed the best sensitivity (57% and 68%) and specificity (100% and 57%) for NLR > 5.8 and RDW/PLT ≤ 0.057 for predicting the severity of HF, respectively. Results showed that NLR and RDW/PLT may have potential for monitoring severity of the disease and the effect of treatment in dogs with HF. Imbalances between indices of circulating blood cells can contribute to immunoinflammatory and antioxidant responses in pathogenesis of canine HF, which may provide us alternative targets to develop new diagnostic and therapeutic strategies in veterinary medicine.

Iron parameters analysis in dogs with myxomatous mitral valve disease.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

Phosphoproteomics analysis of serum from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease.

Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Phosphorylation of proteins, impacting vascular function and cell proliferation, might play a role in the development and progression of PH. Unlike gene or protein studies, phosphoproteomic focuses on active proteins that function as end-target proteins within signaling cascades. Studying phosphorylated proteins can reveal active contributors to PH development. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach. Serum samples were collected from healthy control dogs (n = 28), dogs with DMVD (n = 24), and dogs with DMVD and PH (n = 29). Phosphoproteins were enriched from the serum samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data analysis was performed to identify uniquely expressed phosphoproteins in each group and differentially expressed phosphoproteins among groups. Phosphoproteomic analysis revealed nine uniquely expressed phosphoproteins in the serum of dogs in the DMVD+PH group and 15 differentially upregulated phosphoproteins in the DMVD+PH group compared to the DMVD group. The phosphoproteins previously implicated in PH and associated with pulmonary arterial remodeling, including small nuclear ribonucleoprotein G (SNRPG), alpha-2-macroglobulin (A2M), zinc finger and BTB domain containing 42 (ZBTB42), hemopexin (HPX), serotransferrin (TRF) and complement C3 (C3), were focused on. Their unique expression and differential upregulation in the serum of DMVD dogs with PH suggest their potential as biomarkers for PH diagnosis. In conclusion, this phosphoproteomic study identified uniquely expressed and differentially upregulated phosphoproteins in the serum of DMVD dogs with PH. Further studies are warranted to validate the diagnostic utility of these phosphoproteins.

Aorto-left atrial fistula secondary to aortic infective endocarditis in a dog with a bicuspid aortic valve.

An 11-year-old male neutered American bulldog was presented for evaluation of thrombocytopenia, acute onset of ataxia, and vomiting. A new murmur was auscultated on physical examination. Transthoracic echocardiographic examination revealed a bicuspid aortic valve, vegetative lesions on the aortic valve, and continuous shunting from the aortic root to the left atrium through an aorta to left atrial fistula. The dog was euthanized due to its guarded prognosis and critical condition. Pathological examination confirmed presence of a bicuspid aortic valve, aorto-left atrial fistula, and aortic infective endocarditis. Antemortem blood culture revealed two unusual organisms: Achromobacter xylosoxidans and Fusobacterium mortiferum.

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

OBJECTIVE: 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. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: 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. RESULTS: 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. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Association between echocardiographic indexes and urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in dogs with myxomatous mitral valve disease.

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of tubular damage, and its elevation has been described in human and canine cardiorenal syndrome. The aim was to evaluate the association between echocardiographic indexes and urine NGAL (uNGAL) and uNGAL normalized to urine creatinine (uNGALC) in dogs with MMVD. This is a multicentric prospective cross-sectional study. A total of 77 dogs with MMVD at different ACVIM stages were included. All dogs underwent echocardiography, serum chemistry, and urinalysis. Echocardiographic data analyzed were shortening fraction (SF), left ventricular diastolic (LVIDDn) and systolic (LVIDSn) diameters normalized for body weight, left atrium to aortic root ratio (LA/Ao), maximal (LAVMax) and minimal (LAVMin) left atrial volumes, LA stroke volume (LASV), early diastolic mitral peak velocity (EVmax), EVmax to tissue Doppler E' wave (E/E'), aortic (VTIAo) and mitralic (VTIMit) velocity time integrals and their ratio (VTIMit/VTIAo), and tricuspid regurgitation velocity (TRVmax). In the univariate analysis LASV, TRVmax, LAVMax, LVIDDn, and VTIMit/VTIAo were independent predictors of increased uNGAL and uNGALC; however, only LASV [(OR: 1.96, 95% CI: 1.16 to 3.31) P = 0.01 for NGAL, and (OR: 2.79, 95% CI: 1.50 to 5.17) P < 0.001 for NGALC] and TRVmax [(OR: 1.73, 95% CI: 1.20-2.51) P = 0.002 for NGAL, and (OR: 1.50, 95% CI: 10.07-2.10) P = 0.015 for NGALC] remained statistically significant in the multivariable analysis. Based on our results, LASV and TRVmax are associated with increased uNGAL and uNGALC. These parameters might detect dogs with MMVD at higher risk of developing kidney damage.

Utility of focused cardiac ultrasonography training in veterinary students to differentiate stages of subclinical myxomatous mitral valve disease in dogs.

BACKGROUND: Differentiation of the subclinical phases of myxomatous mitral valve disease (MMVD) in dogs relies heavily on echocardiography. Focused cardiac ultrasonography (FCU) is a point-of-care technique that can assess heart size. HYPOTHESIS/OBJECTIVES: Veterinary students trained in FCU can differentiate dogs with subclinical MMVD based on left ventricular (LV) and left atrial (LA) dimensions. ANIMALS: Forty-eight dogs with subclinical MMVD. METHODS: Veterinary students were trained to measure LV dimension and LA-to-aortic root dimension ratio (LA : Ao) using FCU. Dogs were categorized into 2 cohorts based on whether or not the LV normalized internal diastolic dimension was ≥1.7 and LA : Ao was ≥1.6. Agreement between FCU and echocardiographic studies performed by cardiologists was evaluated. RESULTS: One-hundred and forty-six FCU examinations were performed by 58 veterinary students on 48 dogs. Overall agreement between students and cardiologists was moderate (Fleiss' kappa, 0.54; 95% confidence interval [CI], 0.39-0.69; P < .001). Percentage accuracy in observations with heart dimensions less than the cutoffs (86/89, 97%) was significantly higher than in observations in with larger hearts (31/57, 54%; P < .001). Agreement increased from moderate to good as heart sizes became more extreme. Degree of confidence by students in performing FCU was significantly higher at the end vs start of the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Categorization of dogs with subclinical MMVD by veterinary students using FCU was associated with moderate to good agreement with echocardiography. Focused cardiac ultrasonography is a point-of-care method that can help assess clinical stage in dogs with subclinical MMVD.

Effects of acute atrial fibrillation and cardioversion on left and right atrial pressures in a dog.

The occurrence of right-sided congestive heart failure (CHF) in dogs with left-sided heart disease is well-recognized, but its mechanisms are incompletely understood. A 12-year-old Maltese dog was admitted to the clinic for left atrial decompression to treat recurrent CHF due to severe myxomatous mitral valve disease (MMVD). Left atrial decompression was successful but atrial fibrillation (AF) occurred during the procedure. Electric cardioversion restored normal sinus rhythm (NSR) and the dog's recovery was uneventful. This sequence of events made it possible to study intracameral pressures individually in each atrium in a dog with naturally occurring MMVD during AF and again during NSR. Although pressures in both atria declined following cardioversion, the right atrial pressure declined to a greater degree. These findings indicated a disproportionate effect of AF on right atrial pressure. This difference was noteworthy given the long-standing clinical observation that dogs with MMVD have a higher prevalence of right-sided CHF when AF is present. Key clinical message: A dog with MMVD had a greater reduction in right atrial pressure than in left atrial pressure when its AF was cardioverted as part of a cardiac catheterization procedure. This observation proposed a mechanism for the well-known but unexplained observation that dogs with MMVD manifest right-sided CHF disproportionately more often when they have AF.

Effets de la fibrillation auriculaire aiguë et de la cardioversion sur les pressions auriculaires gauche et droite chez un chien. La présence d'une insuffisance cardiaque congestive du côté droit (ICC) chez les chiens atteints d'une cardiopathie du côté gauche est bien connue, mais ses mécanismes ne sont pas complètement compris. Un chien maltais de 12 ans a été admis à la clinique pour une décompression auriculaire gauche afin de traiter une ICC récurrente due à une grave maladie myxomateuse de la valvule mitrale (MMVD). La décompression auriculaire gauche a réussi, mais une fibrillation auriculaire (FA) s'est produite pendant la procédure. La cardioversion électrique a rétabli le rythme sinusal normal (NSR) et la récupération du chien s'est déroulée sans incident. Cette séquence d'événements a permis d'étudier les pressions individuellement dans chaque oreillette chez un chien atteint de MMVD d'origine naturelle pendant la FA et à nouveau pendant la NSR. Bien que les pressions dans les deux oreillettes aient diminué après la cardioversion, la pression de l'oreillette droite a diminué dans une plus grande mesure. Ces résultats ont indiqué un effet disproportionné de la FA sur la pression auriculaire droite. Cette différence était remarquable compte tenu de l'observation clinique de longue date selon laquelle les chiens atteints de MMVD ont une prévalence plus élevée d'ICC du côté droit en cas de FA.Message clinique clé :Un chien atteint de MMVD présentait une réduction plus importante de la pression auriculaire droite que de la pression auriculaire gauche lorsque sa FA était cardiovertie dans le cadre d'une procédure de cathétérisme cardiaque. Cette observation propose un mécanisme pour l'observation bien connue mais inexpliquée selon laquelle les chiens atteints de MMVD manifestent une ICC du côté droit de manière disproportionnée plus souvent lorsqu'ils souffrent de FA.(Traduit par Dr Serge Messier).

Relationship between syringomyelia and myxomatous mitral valve disease in Cavalier King Charles spaniels.

BACKGROUND: Syringomyelia (SM) and myxomatous mitral valve disease (MMVD) are highly prevalent in Cavalier King Charles spaniels (CKCS). Cardiac status in CKCS with and without SM is currently unknown. OBJECTIVES: To investigate the association between SM and MMVD severity in CKCS and CKCS with SM with and without clinical signs of SM. ANIMALS: Fifty-five CKCS: 40 with SM (22 symptomatic and 18 asymptomatic) and 15 without SM. METHODS: A combined retrospective and prospective study. MRI and echocardiography were used to diagnose SM and MMVD, respectively. The association between SM and MMVD severity (left ventricle internal diameter in diastole normalized to bodyweight [LVIDDN] and left atrium to aortic ratio [LA/Ao]) were tested using multivariable linear regression analysis adjusting for sex and age. RESULTS: Overall, no significant difference in LVIDDN and LA/Ao was found between CKCS with or without SM. However, CKCS with symptomatic SM had significantly smaller LVIDDN (1.45 [1.30-1.50]) (median [IQR]) and LA/Ao (1.20 [1.10-1.28]) compared to CKCS with asymptomatic SM (1.60 [1.50-1.90] and 1.40 [1.20-1.75]) as well as CKCS without SM (0.24 [0.03-0.45] and 0.30 [0.05-0.56]) (all P values <.03). CONCLUSIONS AND CLINICAL IMPORTANCE: An association between MMVD and SM was not confirmed in this cohort of CKCS, indicating that MMVD and SM do not co-segregate. However, CKCS with symptomatic SM had smaller left ventricle and atrial size compared to CKCS with asymptomatic SM and CKCS without SM.

Efficacy of a mitral regurgitation severity index to predict long-term outcome in dogs with myxomatous mitral valve disease.

BACKGROUND: Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging. HYPOTHESIS/OBJECTIVES: The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all-cause death in dogs with MMVD. ANIMALS: Eight hundred sixty-nine client-owned dogs. METHODS: Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium-to-aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time-dependent receiver-operator characteristic curves quantified prognostic performance. RESULTS: For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9-4.9]; P < .001). MRSI > 173 was predictive of all-cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4-7.5]; P < .001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C. CONCLUSIONS AND CLINICAL IMPORTANCE: MRSI was predictive of outcome (onset of CHF and all-cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula.

Mitral annular disjunction and myxomatous mitral valve disease in a dog.

Mitral annular disjunction (MAD) has been defined as a structural abnormality with separation between the posterior leaflet of the mitral valve and the left atrial wall. It is commonly associated with myxomatous mitral valve disease (MMVD), mitral valve prolapse (MVP), ventricular arrhythmias, and sudden cardiac death in humans, but has not been described in veterinary medicine despite the high prevalence of MMVD in the canine population. The echocardiographic findings in a Chihuahua with MAD, MMVD, and MVP are described. Diagnostic methods and criteria are reviewed and adapted.

Interventricular inflow time difference assessed by dual pulsed-wave Doppler echocardiography in dogs with myxomatous mitral valve disease.

INTRODUCTION: Interventricular inflow time difference (IVID), which is defined as the time interval between the opening of the mitral valve and the opening of the tricuspid valve, hold prognostic value in human patients with heart failure. Few reports regarding IVID are available in dogs. ANIMALS: Ninety dogs with myxomatous mitral valve disease (MMVD) and 47 dogs without heart disease. Dogs with MMVD received unstandardized therapy based on the stage of disease. MATERIALS AND METHODS: This was a prospective cohort study. Dogs were classified into two groups based on IVID: tricuspid opening preceding mitral opening (TOP) and mitral opening preceding tricuspid opening (MOP). The potential influence of the MOP group at enrollment on the primary outcome (cardiac-related death) was determined by Kaplan-Meier analysis. RESULTS: Almost all dogs without heart disease (97.9%) were classified in the TOP group. Twenty-nine dogs (32.2%) were classified in the MOP group. Left heart size, transmitral early diastolic inflow velocity, and right ventricular Tei index were significantly greater in the MOP group compared to those in the TOP group. Cardiac-related death were observed in 34 dogs (40.5%). The dogs in the MOP group at initial examination had shorter survival times than those in the TOP group (586 days vs. >1,831 days; 95% confidence interval, 237-714 days vs. 1,037 days to >1,831 days; P<0.001). CONCLUSIONS: Interventricular inflow time difference is potentially useful for prognostic assessments in dogs with MMVD. Further prospective studies that quantify the repeatability and influence of therapy on IVID are needed.

Mitral valve transcriptome analysis in thirty-four age-matched Cavalier King Charles Spaniels with or without congestive heart failure caused by myxomatous mitral valve disease.

We here report the results of a mitral valve transcriptome study designed to identify genes and molecular pathways involved in development of congestive heart failure (CHF) following myxomatous mitral valve disease (MMVD) in dogs. The study is focused on a cohort of elderly age-matched dogs (n = 34, age ~ 10 years) from a single breed-Cavalier King Charles Spaniels (CKCS)-with a high incidence of MMVD. The cohort comprises 19 dogs (10♀, 9♂) without MMVD-associated CHF, and 15 dogs (6♀, 9♂) with CHF caused by MMVD; i.e., we compare gene expression in breed and age-matched groups of dogs, which only differ with respect to CHF status. We identify 56 genes, which are differentially expressed between the two groups. In this list of genes, we confirm an enrichment of genes related to the TNFß-signaling pathway, extracellular matrix organization, vascular development, and endothelium damage, which also have been identified in previous studies. However, the genes with the greatest difference in expression between the two groups are CNTN3 and MYH1. Both genes encode proteins, which are predicted to have an effect on the contractile activity of myocardial cells, which in turn may have an effect on valvular performance and hemodynamics across the mitral valve. This may result in shear forces with impact on MMVD progression.

Clinical relevance of serum ionized magnesium concentration in dogs with myxomatous mitral valve disease.

BACKGROUND: Hypomagnesemia is associated with a poor prognosis in humans with congestive heart failure (CHF), but studies in veterinary medicine are limited. HYPOTHESIS: Serum ionized magnesium concentration [iMg2+ ] would decrease as CHF progresses compared with the initial diagnostic levels and that lower [iMg2+ ] would be negatively associated with prognosis in dogs with CHF. ANIMALS: A total of 181 client-owned dogs with myxomatous mitral valve disease (MMVD) were included. They were classified into the preclinical stage (NO-CHF, n = 108), stage C (n = 42), and stage D (n = 31) based on the American College of Veterinary Internal Medicine MMVD classification. METHODS: This is a retrospective study from 2 referral centers. The [iMg2+ ] was compared among the NO-CHF, stage C, and stage D groups. Kaplan-Meier curves and the log-rank test were used to compare the incidence of death between groups. Multivariable Cox regression analysis was used to estimate the association of hypomagnesemia with the death. RESULTS: In the stage D group, the [iMg2+ ] was lower than that in the NO-CHF (P < .0001) and stage C groups (P < .003). In the Kaplan-Meier survival analysis, the 1-year cumulative survival rate in hypomagnesemic dogs was 53% compared with 91.5% in normomagnesemic dogs (log-rank test, P < .0001). In the multivariable Cox analysis, lower concentration of [K+ ] and [iMg2+ ], along with higher Evel , were associated with negative prognoses. Specifically, hypomagnesemia was associated with an approximately 4-fold increased risk of death (hazard ratio = 4.015; 95% confidence interval, 1.537-10.488; P = .005). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessing the [iMg2+ ] might serve as a potential marker for estimating the severity and prognosis indirectly in dogs with MMVD. Combining [iMg2+ ] measurement with other diagnostic methods, such as echocardiography, could improve the prognostic evaluation of MMVD in dogs.

Current use of real-time three-dimensional transthoracic echocardiography in animals.

This review includes 36 studies of transthoracic real-time three-dimensional echocardiography (RT3DE) in animals. Most of these studies concern cardiac chamber quantification of the left atrium and left ventricle, in dogs. Comparisons of RT3DE and different two-dimensional echocardiographic (2DE) methods have been reported in dogs with myxomatous mitral valve disease (MMVD), dilated cardiomyopathy, and in healthy control dogs. Comparisons of RT3DE and standard reference methods have been reported in healthy control dogs. In dogs with MMVD, volumetric RT3DE measurements of left atrium do not appear to provide superior prognostic value compared with 2DE methods using Simpson's method of discs in dogs with MMVD. The major advantages of RT3DE compared to 2DE include improvements in visualization of the complex morphology of the mitral valve, the estimation of mitral valve regurgitation, and improved visualization of complex congenital cardiac abnormalities.

Clinical presentation, echocardiographic findings, treatment strategies, and prognosis of dogs with myxomatous mitral valve disease presented with pericardial effusion due to suspected left atrial tear: a retrospective case-control study.

INTRODUCTION/OBJECTIVES: Left atrial tear (LAT) is a life-threatening complication in dogs with myxomatous mitral valve disease (MMVD). The study objective was to describe clinical presentation, echocardiographic findings, treatment strategies, and survival in dogs with LAT compared to a control group of dogs with a similar stage of MMVD but no LAT. ANIMALS AND MATERIALS AND METHODS: Two-center retrospective case-controlled study including 15 dogs with and 15 dogs without LAT was conducted. Clinical and echocardiographic data were reviewed, and survival information were collected. RESULTS: Nine dogs in each group were in stage C of MMVD, while the remaining were in stage B2. No differences between groups were found regarding age, body weight, sex, kidney values, and echocardiography-derived cardiac dimensions. Most reported clinical signs associated with LAT included weakness, respiratory signs, and syncope. Treatment varied and was mainly focused on the management of congestive heart failure. Three dogs with LAT received a pericardiocentesis. All 15 dogs with LAT had died of cardiac causes, five dogs during the first seven days after admission. The median survival time for all 15 dogs with LAT was 52 days compared to 336 days in the control group (P=0.103). When excluding five dogs with LAT that died during the first seven days, the median survival increased to 407 days, not different compared to the control group (P=0.549). CONCLUSIONS: Dogs with MMVD and LAT have a high short-term mortality; however, when surviving the acute phase, the long-term prognosis may not differ from dogs with a similarly advanced degree of MMVD but without LAT.

Determination of radiographic vertebral heart score and vertebral left atrial size cutoffs based on echocardiographic left atrial size in dogs with myxomatous mitral valve disease.

Progression of myxomatous mitral valve disease (MMVD) in dogs is a common cause of left atrial enlargement. Recently, a classification of left atrial (LA) size based on echocardiographic measurement has been proposed. This study aims to determine the radiographic LA size by reporting the cutoff values of VHS and VLAS for different groups of echocardiographic-measured LA size in dogs with MMVD. This retrospective analytical cross-sectional study included dogs diagnosed with MMVD grouped based on the echocardiographic LA size into normal (LA/Ao < 1.6), mild (1.6-1.89), moderate (1.9-2.2), and severe enlargement (>2.2) and were compared with ACVIM classification. VHS and VLAS were measured on the right lateral radiograph for each dog and cutoff values were calculated. One hundred and three dogs with MMVD were included in the study. A very strong positive correlation was observed between LA/Ao ratio and VHS (rs , 0.823, P < .01) or VLAS (rs , 0.834, P < .01). For VHS, a cutoff of 10.7 v, 11 v, and 11.5 v were established for echocardiographic LA thresholds of 1.6, 1.9, and 2.2 with a sensitivity of 79%, 92%, and 90% and a specificity of 97%, 90.7%, and 78.1%, respectively. For VLAS, a cutoff of 2.5 v, 2.7 v, and 2.9 v were established for echocardiographic LA cutoffs of 1.6, 1.9, and 2.2 with a sensitivity of 73%, 80%, and 83.3% and a specificity of 94%, 92%, and 86.3%, respectively. The results of this study may facilitate clinical decisions based on radiographic examination in dogs with myxomatous mitral valve disease.