Myxomatous Mitral Valve Disease In Dogs Research Articles

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

Hypomagnesemia is associated with a poor prognosis in humans with congestive heart failure (CHF), but studies in veterinary medicine are limited. 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. 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. 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. 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). 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.

Prognostic Efficacy of Complete Blood Count Indices for Assessing the Presence and the Progression of Myxomatous Mitral Valve Disease in Dogs.

This study investigated the complete blood count (CBC) indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in dogs with myxomatous mitral valve disease (MMVD) and analyzed their correlation with conventional biomarkers, as well as the effect of CBC indices on survival time in dogs with MMVD. Medical records of 75 healthy controls and 249 dogs with MMVD from March 2015 to October 2022 were analyzed. The NLR, MLR, and PLR were calculated by dividing the absolute counts of the CBC parameters. Dogs with MMVD had significantly higher NLR, MLR, and PLR than healthy dogs (all p < 0.0001), especially those in the symptomatic MMVD group with pulmonary edema (p < 0.0001, p = 0.0002, and p = 0.0387, respectively). The NLR and MLR were significantly correlated with N-terminal pro-B type natriuretic peptide levels (both p < 0.0001). The CBC indices showed potential as biomarkers for detecting the presence of MMVD (all p < 0.0001) and severity of MMVD (p < 0.0001, p < 0.0001, and p = 0.006, respectively) using receiver operating characteristic curve analysis. The negative effects of increased NLR, MLR, and PLR on survival were confirmed using Kaplan-Meier curve analysis. In conclusion, NLR, MLR, and PLR could be cost-effective and readily available potential diagnostic and prognostic biomarkers for MMVD in dogs.

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.

Prognostic value of serum cystatin C concentration in dogs with myxomatous mitral valve disease.

Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys-C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. This study aims to investigate the prognostic value of Cys-C in dogs with MMVD. Fifty client-owned small-breed dogs with MMVD were included in this study. This is a retrospective, cross-sectional study. The prognostic value of serum Cys-C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan-Meier survival curves for MMVD-specific survival in dogs stratified into high and low Cys-C groups were generated and analyzed using the log-rank test. Serum Cys-C concentrations were significantly associated with MMVD-related death (P < .01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950-13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767-12.270). The high Cys-C group (n=14) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n=36; P < .01). In dogs with normal blood creatinine concentrations, the high Cys-C group (n=10) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n=36; P < .01). High serum Cys-C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys-C could be a predictor of MMVD prognosis even in dogs with normal blood creatinineconcentration.

Retrospective evaluation of clinical signs, clinical course, and prognosis between dogs with left atrial rupture secondary to myxomatous mitral valve disease and those with neoplastic cardiac tamponade (2015-2019): 70 cases.

To describe the clinical signs, clinical course, and prognosis of suspected left atrial rupture (LAR) secondary to myxomatous mitral valve disease (MMVD) in dogs and to compare them with dogs with suspected neoplastic cardiac tamponade (NCT). Retrospective study from November 2015 to October 2019 SETTING: An out-of-hours Emergency Animal Hospital. Twenty-three dogs with LAR secondary to MMVD (LAR group) and 47 dogs with NCT (NCT group). None. The following were the characteristics of the study population (LAR group vs NCT groups) with P<0.05 as the significance threshold: male sex, 83%vs 66%; median age, 11.9 vs 12.5 years; and median weight, 3.8 vs 6.4kg (P<0.001). Chihuahuas and Miniature Dachshunds were overrepresented in the LAR and NCT groups, respectively. Statistically different clinical findings between the 2 groups were as follows (LAR vs NCT): pulmonary edema, 43%vs 0%; pericardial thrombus, 70%vs 6% (P<0.001); ineffectiveness of pericardiocentesis (whether aspiration of pericardial fluid was successful or not), 58%vs 2% (P<0.001); mortality rate within 48hours of visiting hospital, 35%vs 9% (P<0.01). No significant difference was observed in survival time after discharge between the 2 groups. The proportion of dogs with a diagnosis of LAR secondary to MMVD in dogs with cardiac tamponade was higher than the previously reported rate. Furthermore, the frequency of pulmonary edema, ineffectiveness of pericardiocentesis, and short-term mortality rate was higher in the LAR group than in the NCT group.

Management of Chronic Congestive Heart Failure Caused by Myxomatous Mitral Valve Disease in Dogs: A Narrative Review from 1970 to 2020.

Simple SummaryMyxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in dogs. The progression of the disease and the increasing severity of valvular regurgitation cause a volume overload of the left heart, leading to left atrial and ventricular remodeling and congestive heart failure (CHF). The treatment of chronic CHF secondary to MMVD in dogs has not always been the same over time. In the last fifty years, the drugs utilized have considerably changed, as well as the therapeutic protocols. Some drugs have also changed their intended use. An analysis of the literature concerning the therapy of chronic heart failure in dogs affected by this widespread degenerative disease is not available; a synthesis of the published literature on this topic and a description of its current state of art are needed. To the authors’ knowledge, a review of this topic has never been published in veterinary medicine; therefore, the aim of this study is to overview the treatments of chronic CHF secondary to MMVD in dogs from 1970 to 2020 using the general framework of narrative reviews.The treatment of chronic congestive heart failure (CHF), secondary to myxomatous mitral valve disease (MMVD) in dogs, has considerably changed in the last fifty years. An analysis of the literature concerning the therapy of chronic CHF in dogs affected by MMVD is not available, and it is needed. Narrative reviews (NRs) are aimed at identifying and summarizing what has been previously published, avoiding duplications, and seeking new study areas that have not yet been addressed. The most accessible open-access databases, PubMed, Embase, and Google Scholar, were chosen, and the searching time frame was set in five decades, from 1970 to 2020. The 384 selected studies were classified into categories depending on the aim of the study, the population target, the pathogenesis of MMVD (natural/induced), and the resulting CHF. Over the years, the types of studies have increased considerably in veterinary medicine. In particular, there have been 43 (24.29%) clinical trials, 41 (23.16%) randomized controlled trials, 10 (5.65%) cross-over trials, 40 (22.60%) reviews, 5 (2.82%) comparative studies, 17 (9.60%) case-control studies, 2 (1.13%) cohort studies, 2 (1.13%) experimental studies, 2 (1.13%) questionnaires, 6 (3.40%) case-reports, 7 (3.95%) retrospective studies, and 2 (1.13%) guidelines. The experimental studies on dogs with an induced form of the disease were less numerous (49–27.68%) than the studies on dogs affected by spontaneous MMVD (128–72.32%). The therapy of chronic CHF in dogs has considerably changed in the last fifty years: in the last century, some of the currently prescribed drugs did not exist yet, while others had different indications.

Reference intervals for echocardiographic measurements in healthy Chihuahua dogs.

Chihuahuas are one of the most common small breed dogs in Japan, and this breed is known to be predisposed to myxomatous mitral valve disease (MMVD). Echocardiographic assessment is essential for definitive diagnosis of MMVD in dogs as well as determining the stage. Because the Chihuahua’s body size is the smallest among the dog breeds and the widely used echocardiographic reference range is established on the basis of larger dogs, it is unclear whether the existing reference range can be applied to the Chihuahua breed as well. Therefore, this study aimed to determine an echocardiographic reference range for Chihuahua dogs. The left atrial short-axis diameter (LA), aortic valve short-axis diameter, interventricular septum thickness at end-diastole, left ventricular internal dimension at end-diastole (LVIDd), and left ventricular posterior wall thickness at end-diastole from 47 healthy Chihuahuas were analyzed. These parameters increased logarithmically as body weight increased. Furthermore, LA and LVIDd were within the previously established reference range generated primarily from multiple breeds of moderate to large breed dogs.

Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST).

BackgroundThe renin‐angiotensin‐aldosterone system (RAAS), when chronically activated, is harmful and RAAS‐suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people.Hypothesis/ObjectivesTo determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE‐I), benazepril, and spironolactone, would be superior to benazepril alone.AnimalsFive hundred and sixty‐nine client‐owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10‐days' duration.MethodsAfter initial stabilization, dogs were randomized into a positive‐controlled, double‐blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d.ResultsA significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32‐0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59‐0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups.Conclusion and Clinical ImportanceThe combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.

Assessment of Vertebral Left Atrial Size and C-reactive Protein in Dogs With Myxomatous Mitral Valve Disease

Recently, a new method of evaluating left atrial size called vertebral left atrial size (VLAS) was introduced in dogs. Total 155 dogs were examined at the Veterinary Medical Teaching Hospital of Chungnam National University. In this study, myxomatous mitral valve disease (MMVD) stage and VLAS showed a significant correlation in those dogs. Also, the relationship between C-reactive protein (CRP) and VLAS has yet to be examined. We found a strong positive correlation between VLAS and CRP—a significant increase in CRP was observed with increasing VLAS values. Thus, it would be beneficial to measure VLAS besides employing the current radiological and echocardiographic methods when evaluating heart size. Measuring VLAS could be an additional diagnostic tool for diagnosing MMVD in dogs.

Use of radiographic measurements to diagnose stage B2 preclinical myxomatous mitral valve disease in dogs.

To investigate the usefulness of radiographic measures of the left atrium and ventricle as surrogates for echocardiographic criteria in identifying dogs with stage B2 preclinical myxomatous mitral valve disease (MMVD). 56 client-owned dogs with preclinical mitral regurgitation attributed to MMVD examined between April 19, 2016, and November 22, 2017. Medical records were retrospectively searched, and data collected included age, body weight, heart murmur grade, and echocardiographic and radiographic measurements. Dogs were grouped according to whether they did (case dogs) or did not (control dogs) meet echocardiographic criteria used to identify dogs with stage B2 MMVD. Measurements for lateral thoracic radiographic variables normalized to vertebral body units (VBUs) were obtained, and results were analyzed to identify variables that could best discriminate between case and control dogs. Three radiographic variables of left atrial size (vertebral left atrial size [VLAS], left atrial width, and the combined variable of VLAS + left atrial width) most accurately distinguished control dogs from case dogs, and the VLAS was the simplest and fastest to perform in a clinical setting. The optimal cutoff for VLAS was 2.5 VBUs (sensitivity, 70%; specificity, 84%; and likelihood ratio, 4.38), with VLAS ≥ 2.5 VBUs for case dogs. The maximum specificity cutoff for VLAS was 3.0 VBUs (sensitivity, 40%; specificity, 96%; and likelihood ratio, 10.0), with VLAS ≥ 3.0 VBUs for case dogs. Results indicated that when echocardiography is unavailable, radiographic VLAS ≥ 3 VBUs could be used with minimal risk of false-positive diagnosis of stage B2 MMVD in dogs.

Serial measurements of cardiac troponin I in heart failure secondary to canine mitral valve disease

Serial measurements of cardiac troponin I (cTnI) levels are considered to be better predictors of cardiac death than single-time-point analyses in human medicine. We hypothesised that cTnI levels could reflect...

Tricuspid annular plane systolic excursion-to-aortic ratio provides a bodyweight-independent measure of right ventricular systolic function in dogs

ObjectivesTo evaluate whether tricuspid annular plane systolic excursion (TAPSE) can be normalized to aortic valve (Ao) measurements in dogs. To determine TAPSE:Ao reference intervals for healthy dogs and examine diagnostic performance of TAPSE:Ao in dogs with pulmonary hypertension (PH). AnimalsOne hundred and thirty-seven healthy adult dogs; 115 dogs with myxomatous mitral valve disease (MMVD) but no PH; 91 dogs with PH. MethodsA combined prospective and retrospective study. Full echocardiographic evaluations were performed on all dogs; TAPSE was indexed to Ao to produce a unitless TAPSE:Ao. Reference intervals for TAPSE:Ao were generated, and TAPSE:Ao was regressed on tricuspid regurgitant jet velocity in dogs with PH and on LA:Ao in dogs with MMVD without PH. Diagnostic test analysis was used to examine the ability of TAPSE:Ao to identify severe PH. An adjusted TAPSE:Ao (TAPSE:Ao(adj)) was derived to account for MMVD in dogs with PH. ResultsThe ratio, TAPSE:Ao, removed the effect of bodyweight from TAPSE measurements. Healthy dogs had TAPSE:Ao > 0.65. The ratio, TAPSE:Ao, showed a linear negative relationship with tricuspid regurgitation velocity and positive relationship with LA:Ao. The adjusted ratio, TAPSE:Ao(adj), increased the sensitivity of diagnosis of PH in dogs with moderate-severe MMVD without affecting the diagnosis of PH in dogs with PH and with no or mild MMVD. ConclusionsThe ratios, TAPSE:Ao and TAPSE:Ao(adj), are a bodyweight-independent means of assessing right ventricular systolic function in dogs and for identifying severe PH in dogs with or without MMVD.

Medical management of myxomatous mitral valve disease: An evidence-based veterinary medicine approach.

Myxomatous mitral valve disease (MMVD) is the most common heart disease of dogs. The current management of MMVD in dogs is mostly pharmacological, and the recommendations for treatment are based on a number of veterinary studies. Notwithstanding the current consensus regarding the medical management of MMVD, there remains active debate as to which drugs are the most effective. In order to understand how recommendations are constructed in the pharmacological management of diseases, the veterinarian needs to understand the concept of evidence-based veterinary medicine, and how the findings of these studies can be applied in their own practices. This review summarises the current veterinary literature and explains how the consensus regarding the management of MMVD has been reached. This review highlights the limitations of veterinary studies in order to provide veterinary practitioners with a sense of the difficulty there is in establishing the benefit of one treatment over the other. Veterinarians should therefore apply treatment recommendations based on the best evidence, integrated with a pathomechanistic understanding of the disease process and clinical experience.

Plasma atrial natriuretic peptide is an early diagnosis and disease severity marker of myxomatous mitral valve disease in dogs

The aim of this study was to retrospectively assess the clinical usefulness of plasma atrial natriuretic peptide (ANP) concentrations for determining the severity of myxomatous mitral valve disease (MMVD) in dogs. Plasma ANP levels were found to be significantly higher in dogs with MMVD compared to healthy dogs, and plasma ANP levels increased significantly in dogs with progressive heart failure. In dogs with MMVD, stepwise regression analysis revealed that the left atrium/aorta ratio and fractional shortening could be used to predict the plasma ANP concentration. These results indicated that plasma ANP rose with an increase in the volume overload of the left side of the heart. Plasma ANP discriminated cardiomegaly from non-cardiomegaly caused by asymptomatic MMVD. We conclude, therefore, that plasma ANP concentrations may be a clinically useful tool for early diagnosis of asymptomatic MMVD in dogs.

Increased NADPH-Diaphorase Activity in Canine Myxomatous Mitral Valve Leaflets

Comparable pathological changes in the mitral valve have been described in dogs, pigs and human patients with myxomatous mitral valve disease (MMVD), i.e., primary mitral valve prolapse. The progressive myxomatous changes are probably a response to repeated impact on the leaflets, and endothelial stress or damage probably plays a central role in the pathogenesis. Little, however, is known about the vasoactive substances that mediate the subendothelial changes. The aim of this study was to investigate the expression of nitric oxide synthase (NOS) in canine mitral valve leaflets and to relate the findings to MMVD changes. The mitral valve was taken post mortem from 12 dogs (six males and six females) and a whole valve NADPH (the reduced form of nicotinamide-adenine dinucleotide phosphate) diaphorase (NADPH-d) reaction was performed. Macroscopical (semiquantitative) and microscopical (computer image analysis) evaluations of the staining due to NADPH-d activity were performed at four specific areas of the valve and related to microscopical signs of MMVD and gross signs of thickening or prolapse, or both. Macroscopically, the NADPH-d colour grade was correlated with the degree of MMVD ( P=0.01). In addition, endothelial NADPH-d staining intensity was correlated with macroscopical signs of disease ( P=0.004) as well as with collagen degeneration ( P=0.008) and deposition of mucopolysaccharides ( P=0.02). Age, gender and specific area of the valve did not seem to influence the NADPH-d activity. In conclusion, increased NADPH-d activity, suggesting increased NOS expression, was found in areas of the mitral valve with myxomatous changes. This indicates that nitric oxide (NO) may play a role in the pathogenesis of MMVD in dogs.