Myxomatous Mitral Valve Degeneration Research Articles

Pulmonary-vein-to-pulmonary-artery ratio can be utilized to evaluate myxomatous mitral valve disease progression in dogs.

To evaluate the diagnostic value of pulmonary-vein-to-pulmonary-artery ratio (PV:PA) in dogs with myxomatous mitral valve degeneration (MMVD), classified according to the American College of Veterinary Internal Medicine (ACVIM) consensus guidelines. 80 client-owned dogs with either MMVD (n = 65) or no cardiovascular disease (control group; n = 15) between August 5, 2020, and July 19, 2023. This is a retrospective study. Dogs with MMVD were classified according to ACVIM consensus guidelines. Echocardiograms, thoracic radiographs, and other measurements needed in this study were reviewed in all dogs. Spearman correlation was used to determine the correlation between the PV:PA and the following variables: vertebral heart size, vertebral left atrial size, left-atrium-to-aorta ratio, normalized left ventricular internal diameter, and peak transmitral early diastolic velocity. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of PV:PA in distinguishing between stages B1 and B2 and stages B2 and C. All conventional indices showed correlations with PV:PA. The area under the ROC curve (AUC) for stages B1 and B2 was 0.83, and the cutoff value for differentiating stage B2 was 1.52. The AUC for stages B2 and C was 0.81, and the cutoff value for differentiating stage C was 2.09. PV:PA was significantly different between control and the stage B1 group, stage B1 and B2 group, and stage B2 and C group. PV:PA can be an index that can be used in evaluating MMVD dogs.

Pulmonary Hypertension Secondary to Myxomatous Mitral Valve Disease in Dogs: Current Insights into the Histological Manifestation and Its Determining Factors

Pulmonary venous hypertension (PVH) is caused by deteriorating left ventricular function. The most common cause of PVH in dogs is myxomatous mitral valve degeneration (MMVD). It causes left ventricular volume overload and an increase in left atrial and pulmonary venous pressure (PVH), which leads to pulmonary vascular wall remodeling and contributes to the perpetuation and worsening of PVH. Pulmonary vascular wall remodeling is also characteristic of pulmonary arterial hypertension (PAH). However, the changes in PVH arise secondary to heart failure and vascular remodeling progresses as the disease progresses. On the other hand, PAH is a primary disease that can be triggered, for example, by the use of certain drugs. Similar structural changes may suggest the influence of similar pathophysiological mechanisms or the intermediation of similar mediators. Therefore, this article discusses recent and hitherto uncommented findings elucidating the pathophysiology of the processes and influences on the pattern of histological changes observed in pulmonary hypertension secondary to degenerative mitral valve disease. In particular, we focus on the activity of factors such as endothelin, serotonin, and nitric oxide, which are involved in pulmonary vascular wall remodeling in both PVH and PAH.

Self-Reported Utilization of International (ACVIM Consensus) Guidelines and the Latest Clinical Trial Results on the Treatment of Dogs with Various Stages of Myxomatous Mitral Valve Degeneration: A Survey among Veterinary Practitioners.

Myxomatous mitral valve degeneration is the most common canine heart disease. Several clinical trials have investigated various treatments. The latest recommendations are published in the ACVIM consensus guidelines (2019). Our study aimed to investigate how closely veterinary practitioners apply the treatment recommendations of these guidelines and the latest clinical trials. An online survey was sent to Dutch and Belgian veterinary practices via digital channels. The data from 363 fully completed surveys were analyzed. For stage B1 disease, 93% recommended, correctly, no treatment. For stage B2 disease, 67% of the respondents recommended starting pimobendan as monotherapy. For chronic treatment of stage C disease, 16 different drug combinations were mentioned, but nobody recommended surgery. Only 48% of the respondents recommended the only evidence-based drug combination: a loop diuretic with pimobendan. A concerning finding was the simultaneous prescription of two loop diuretics, by 19% of the respondents. Treatment recommendations showed an increasing variation with more advanced disease stages from B1 through B2 to C. This reflects the increasing disagreement among the panelists who prepared the ACVIM consensus guidelines. Practitioners of our study seem to practice more evidence-based medicine than veterinary cardiologists, as it was reported in a recent survey-based study.

Effects of Mitral Valve Surgery on Ventricular Arrhythmia in Mitral Valve Prolapse Patients: Five-Year Eollow-up.

Aim To evaluate the effect of mitral valve (MV) repair and replacement on the incidence of ventricular arrhythmias (VA) and to identify risk factors for the persistence of VA in patients with MV prolapse and severe mitral regurgitation (MR) during a mid-term follow-up.Material and methods A single-site observational, prospective study successively enrolled 30 patients (mean age, 55.2±9.9 years, 60% men) who underwent MV repair or replacement for severe MR due to MV prolapse or chordal avulsion. Transthoracic echocardiography and Holter monitoring were performed in all patients before and annually after surgery. A pathomorphological study of MV fragments excised during surgery was performed.Results During the five-year follow-up period (144 person-years), one case of sudden cardiac death outside a health care facility was recorded. MR severity progressed in three patients after MV repair. The total number of all VAs decreased during the follow-up period, with a significant decrease in the number of paroxysms of unstable ventricular tachycardia during the first two years after surgery. The presence of VA in the postoperative period was correlated with the severity of postoperative left ventricular (LV) remodeling: end-diastolic volume (EDV) (rs=0.69; p=0.005), LV ejection fraction (EF) (rs = -0.55; p=0.004) and severity of MV myxomatous alterations according to histological study data (rτ=0.58; p=0.045). The beta-blocker treatment did not influence the VA frequency and severity (rs= -0.18; p=0.69). According to a univariate regression analysis only EDV (p = 0.001), LVEF <50% (p = 0.003), and myxomatous MV degeneration (p = 0.02) were risk factors for persistent ventricular tachycardia in the postoperative period.Conclusion Surgical intervention on MV in patients with MV prolapse and severe MR decreased the number of cases of malignant VAs and was correlated with the postoperative changes in LV volume and function, as well as the severity of MV myxomatous alterations.

Self-Reported Utilization of International Guidelines for Staging Dogs with Myxomatous Mitral Valve Degeneration: A Survey among Veterinary Practitioners.

ACVIM developed and published guidelines for staging myxomatous mitral valve degeneration in dogs in 2009. An updated version was published in 2019. The present study aimed to investigate whether these guidelines are actually used by the intended public more than a decade after their first publication. An online survey was distributed among Dutch and Belgian veterinarians through online channels and mailing lists. Of the 524 responses, only 363 complete surveys were analyzed. The ACVIM guidelines are used by 60% of the respondents. Veterinarians find it more difficult to differentiate stage B1 from B2 in asymptomatic dogs compared to diagnosing stage C. Three-quarters of the respondents would recommend echocardiography for an incidentally detected new murmur with an intensity of 3 out of 6 in an adult dog. Two-thirds of the respondents find coughing a convincing finding for stage C disease. Close to half of the respondents associate a horizontal, dull percussion line with pulmonary edema. For confirming cardiogenic pulmonary edema, 98% of the respondents used thoracic radiographs. Veterinary practitioners might not have the expected training and equipment to be able to apply the guidelines in their practices, especially in the differentiation of stage B1 from stage B2.

Impact of a combination of pimobendan, furosemide, and enalapril on heart rate variability in naturally occurring, symptomatic, myxomatous mitral valve degeneration dogs

BackgroundPimobendan, diuretics, and an angiotensin-converting enzyme inhibitor (ACEi) are widely used for the management of chronic valvular heart disease in dogs; however, the effects of that combination on heart rate variability (HRV) are unknown. The purpose of this study was to assess the HRV of symptomatic myxomatous mitral valve degeneration (MMVD) dogs in response to therapy with a combination of pimobendan, diuretics, and ACEi.ResultsMMVD stage C (n = 17) dogs were enrolled and a 1-hour Holter recording together with echocardiography, blood pressure measurement, and blood chemistry profiles were obtained before and 1, 3, and 6 months after oral treatment with pimobendan (0.25 mg/kg), enalapril (0.5 mg/kg), and furosemide (2 mg/kg) twice daily. The results revealed that MMVD stage C dogs at the baseline had lower values of time-domain indices, low frequency (LF), high frequency (HF), and total power, as well as higher value of LF/HF. Triple therapy significantly increases these parameters in MMVD stage C dogs (P < 0.05). A positive moderate correlation was observed between time domain parameters and a left ventricular internal diastole diameter normalized to body weight (P < 0.05).ConclusionsIt can be concluded that MMVD stage C dogs possess low HRV due to either the withdrawal of parasympathetic tone or enhanced sympathetic activation, and a combination therapy was shown to enhance cardiac autonomic modulation inferred from the increased heart rate variability. Therefore, a combination therapy may be useful for restoring normal autonomic nervous system activity in dogs with MMVD stage C.

Use of serum osmolality to identify heart disease stage in dogs and relationship to mathematical chloride correction.

Heart failure-associated hypochloremia can be depletional from diuretics or dilutional from water retention. Serum osmolality reflects water balance but has not been evaluated in dogs with heart disease. To determine if serum osmolality is related to heart disease stage and amount of mathematical correction of serum chloride (Cl- ) concentrations in healthy dogs and dogs with myxomatous mitral valve degeneration (MMVD). Seventy-seven dogs (20 healthy, 25 Stage B MMVD, 32 Stage C/D MMVD). Serum Cl- concentrations were mathematically corrected. Osmolality was calculated (calOsm) and directly measured by freezing point depression (dmOsm) and compared by Bland-Altman analysis. Biochemical variables and osmolality were compared among healthy, Stage B, and Stage C/D dogs. Correlations were explored between osmolality and biochemical variables. Median and range are presented. P < .05 was considered significant. The calOsm was different among groups (P = .003), with Stage B (310 mOsm/kg; 306, 316) and C/D dogs (312 mOsm/kg; 308, 319) having higher calOsm than healthy dogs (305 mOsm/kg; 302, 308). Osmolality methods were moderately correlated (P < .0001, rs = .46) but with proportional bias and poor agreement. The amount of Cl- correction was negatively correlated with calOsm (P < .0001, rs = -.78) and dmOsm (P = .004, rs = -.33). Serum bicarbonate concentration was negatively correlated with Cl- (P < .0001, rs = -.67). Dogs with Stage B and Stage C/D heart disease had higher calOsm than healthy dogs. Osmolality was inversely related to the amount of Cl- correction, which supports its use in assessing relative body water content. Poor agreement between calOsm and dmOsm prevents methodological interchange.

Evaluation of antioxidant status and lipid peroxidation in dogs with myxomatous mitral valve degeneration stage B1.

Myxomatous mitral valve degeneration (MMVD) is the most common naturally occurring heart disease in dogs. There is a lack of data on antioxidant status and oxidative damage in dogs with MMVD stage B1 according to the American College of Veterinary Internal Medicine (ACVIM B1). The aim of this study was to investigate antioxidant status (plasma vitamin E, lipid-standardized vitamin E (LS-VitE), antioxidant capacity of lipid-(ACL) and water-soluble antioxidants, whole blood glutathione peroxidase and erythrocyte superoxide dismutase), and lipid peroxidation [malondialdehyde (MDA)] in dogs with MMVD ACVIM B1. Serum cholesterol and triglyceride concentrations were measured to calculate LS-VitE. Fourteen dogs with MMVD ACVIM B1 and 12 control dogs were included in the study. Dogs with MMVD had significantly higher vitamin E, ACL, MDA, and cholesterol concentrations and significantly higher LS-VitE values than control dogs. No significant correlations between MDA and antioxidant parameters were determined in either group. In conclusion, oxidative damage to lipids is already present and the antioxidant status is altered but not depleted in dogs with MMVD ACVIM B1. The antioxidant response to increased oxidative damage consists mainly of the activation of fat-soluble antioxidants. Further research is needed to evaluate the efficacy and targets of early antioxidant supplementation to prevent or ameliorate oxidative stress and mitigate disease progression in dogs with early-stage MMVD.

Analysis of Poincaré plot derived from 5-min electrocardiography in dogs with myxomatous mitral valve disease

Background Evaluation of heart rate variability (HRV) is used for risk assessment in a variety of cardiac diseases including myxomatous mitral valve degeneration (MMVD). Objectives To compare the geometric analysis of HRV using visual patterns of Poincaré plot among different classes of MMVD in dogs and to analyse the differences in beat-to-beat variability using tachograms and sequential Poincaré plots among different shapes. Animals and methods Healthy and MMVD dogs were retrospectively reviewed. Five-minute ECG data was used to create Poincaré plots and shapes were compared among groups. Furthermore, a sub-analysis of 50 consecutive R–R intervals was performed. Pearson Chi-square with adjusted standardized residuals was used to compare the categorical data between groups. Results Fifteen healthy dogs and 157 dogs with MMVD were included in the study. Normal and B1 groups showed a predominance of triangular shape (73% and 60% respectively; p < 0.05). In B2 group the predominant shape was comet (40%; p < 0.05) while comet and torpedo were predominant in Ca group (41% and 36% respectively; p < 0.05). Visual geometric analysis revealed a lower dispersion of the cloud clustering towards the left lower corner of the plot with MMVD progression. Diamond and triangle revealed a lower mean heart rate compared to comet and torpedo shapes (p < 0.01). Interclass correlation between 3 observers was 0.906 (95% CI of 0.8 − 0.96). Conclusions Poincaré plot shape changes with MMVD progression suggesting that geometrical analysis of HRV in dogs with cardiac conditions could be a useful tool in the risk assessment and further studies are warranted.

Can cartilage intermediate layer protein 1 (CILP1) use as a novel biomarker for canine myxomatous mitral valve degeneration levels or not?

BackgroundMyxomatous mitral valve degeneration (MMVD) is the most common degenerative heart disease in dogs and is associated with irreversible changes in the valve tissue. Although traditional cardiac biomarkers are efficient for diagnosing MMVD, there are limitations, therefore, it is important to find novel biomarkers. Cartilage intermediate layer protein 1 (CILP1), an extracellular matrix-derived protein, acts as a transforming growth factor-β antagonist and is involved in myocardial fibrosis. This study aimed to evaluate serum CILP1 levels in canines with MMVD. Dogs with MMVD were staged according to the American College of Veterinary Internal Medicine consensus guidelines. Data analysis was performed using the Mann–Whitney U test, Spearman’s correlation, and receiver operating characteristic (ROC) curves.ResultsCILP1 levels were elevated in dogs with MMVD (n = 27) compared to healthy controls (n = 8). Furthermore, results showed that CILP1 levels were significantly higher in stage C group dogs compared to healthy controls. The ROC curve of CILP1 and NT-proBNP were good predictors of MMVD, although no similarity was observed between the two. Left ventricular end-diastolic diameter normalized to the body weight (LVIDdn) and left atrial to aorta dimension (LA/Ao) showed a strong association with CILP1 levels; however, no correlation was observed between CILP1 levels and vertebral heart size (VHS) and vertebral left atrial score (VLAS). The optimal cut-off value was selected from the ROC curve and dogs were classified according to the cut-off value (1.068 ng/mL, sensitivity 51.9%, specificity 100%). Results showed a significant association of CILP1 with cardiac remodeling indicators, such as VHS, VLAS, LA/Ao, and LVIDdn.ConclusionsCILP1 can be an indicator of cardiac remodeling in canines with MMVD and therefore, can be used as an MMVD biomarker.

A Retrospective Study of Radiographic Measurements of Small Breed Dogs with Myxomatous Mitral Valve Degeneration: A New Modified Vertebral Left Atrial Size

A Retrospective Study of Radiographic Measurements of Small Breed Dogs with Myxomatous Mitral Valve Degeneration: A New Modified Vertebral Left Atrial Size

Mitral repair of myxomatous valves with simple annuloplasty: a follow-up up to 12 years

Diffuse myxomatous mitral valve degeneration (DMD) represents a challenge in the reparative mitral valve surgery. A subgroup of patients with symmetrical DMD can be effectively treated with a simple band-annuloplasty with good early and mid-term results. Here, we evaluate the long-term outcomes in terms of freedom from reoperation, recurrence of moderate or severe mitral regurgitation (MR) and overall survival. Between April 2006 and December 2020, patients with DMD causing severe MR and the echocardiographic features of symmetrical bileaflet prolapse, central regurgitant jet(s), annular dilation and no chordal ruptures were treated using a simple annuloplasty with a semi-rigid band. These patients were prospectively collected and retrospectively analysed. Seventy-five patients were enrolled. The mean clinical follow-up time was 104 [standard deviation (SD): 43] months, and echocardiographic follow-up time was 95 (SD: 43) months. The mean age was 54 (SD: 15) years, and 56% were females. Long-term overall survival was 98.2% [standard error (SE): 1.8], 93.7% (SE: 4.7) and 93.7% (SE: 4.7) at 4, 8 and 12 years, respectively. The freedom from reoperation was 100% at 4 and 8 years and 94.1% (SE: 5.7) at 12 years. The freedom from recurrent moderate or severe MR was 98.3% (SE: 1.7), 98.3% (SE: 1.7) and 92.8% (SE: 5.5) at 4, 8 and 12 years, respectively. Mitral repair with the simple band-annuloplasty for the treatment of MR due to symmetrical DMD seems to be stable and effective in the long term.

Mitral valvuloplasty with left atrial appendage closure and pacemaker implantation in a dog with severe myxomatous mitral valve degeneration: a case report

BackgroundMitral valvuloplasty (MVP) has been widely recognized as a treatment option for myxomatous mitral valve disease (MMVD). However, postoperative complications such as thromboembolism, arrhythmia, and pancreatitis in some cases have resulted in death. We treated a dog with severe MMVD complicated by impaired sinus function with MVP and pacemaker implantation. Also, due to an intrinsic procoagulant state and severe arrhythmia after the MVP, left atrial appendage (LAA) closure was performed to reduce the postoperative risk of thrombosis.Case presentationAn 11-year-old castrated 7.5-kg male Miniature Schnauzer with a history of congestive heart failure was brought to Shiraishi Animal Hospital for MMVD surgical treatment. Echocardiography revealed an enlarged left atrium and ventricle secondary to MMVD. Sinus arrest with 2 to 3-second periods of asystole was identified by electrocardiogram. Mitral valvuloplasty was performed with cardiopulmonary bypass to treat the MMVD. After coronary reperfusion, there was no spontaneous electrical activity. Cardiac arrest continued. Based on this surgical outcome, a permanent pacemaker was implanted. In addition, LAA closure with an AtriClip was performed to prevent intra-atrial thrombus formation. Cardiac remodeling and congestion were ameliorated after surgery. Sinus rhythm was restored 5 days postoperatively; however, the patient continued pacemaker dependent. All cardiac drugs were discontinued 3 months after surgery. The owner reported no postoperative complications (i.e., thrombosis), and the patient was brought for a check-up 4 months after the operation in good health.ConclusionsFor surgical MMVD cases complicated with impaired sinus function, the chances of spontaneous sinus rhythm are low, requiring pacemaker implantation. LAA closure may be considered to protect against decreased atrial function after mitral valvuloplasty and prevent intra-atrial thrombus formation.

The potential role of microRNA as bio markers in canine congestive heart failure

ObjectiveIn our focus regarding microRNA, single‐stranded, small non‐coding RNAs, we aim to understand miRNA's roll and functional importance concerning congestive heart failure (CHF) and myxomatous mitral valve degeneration (MMVD). Characterizing expression profiles of circulating microRNAs via genome‐wide sequencing for dogs with CHF secondary to MMVD.Animals8 healthy client‐owned dogs and 8 middle age‐matched client‐owned dogs with CHF secondary to MMVD.ProceduresBlood samples were collected before administering cardiac medications for the management of CHF. Quantitative reverse transcription PCR (qRT‐PCR) assays were used to validate expression profiles of differentially expressed circulating microRNAs identified from NGS analysis of dogs with CHF.Conclusion and Clinical RelevanceAwaiting data indicating the patterns of microRNA expression are distinctive and denote molecular biomarkers with CHF in dogs with MMV.

Amlodipine decreases mitral regurgitation volume in dogs over 7 days: A study of 24 dogs with myxomatous mitral valve degeneration

BackgroundAmlodipine, a dihydropyridine calcium‐channel blocker, is currently being investigated as a treatment for myxomatous mitral valvular degeneration (MMVD). However, the effects of amlodipine on moderate or severe spontaneous MMVD, based on changes in echocardiographic indices, remain unclear.AnimalsClient‐owned small‐breed dogs (n = 24) with naturally occurring MMVD of the American College of Veterinary Internal Medicine (ACVIM) stage B2 or higher.MethodsBasic dog information including previous medication treatments were recorded. All subjects received amlodipine 0.1 mg/kg, administered per os, twice daily for 7 days, in addition to their existing medication. We measured systolic blood pressure, obtained x‐ray, echocardiography, blood test data before and after 1 week of amlodipine administration.ResultsLeft ventricular end‐diastolic internal diameter, left atrial diameter and E wave reduced statistically after 1 week of amlodipine treatment (all p < 0.001). No adverse effects were reported.ConclusionsThese findings suggest that low‐dose amlodipine should be considered as treatment for dogs with ACVIM stage B2‒C MMVD.

Mitral valve repair for myxomatous mitral regurgitation; Respect or Resect

Background: The superiority of mitral repair using resection of the posterior leaflet versus neo-artificial chordea is still debatable. The objective of this study was to compare leaflet resection versus chordal replacement for mitral valve repair in patients with isolated myxomatous degeneration of the posterior mitral valve leaflet. &#x0D; Methods: This study was conducted on 199 patients with severe symptomatic mitral regurgitation due to myxomatous mitral valve degeneration. Patients were grouped into two groups: Group (1): Respect technique which included 76 patients who had limited resection of the anterior leaflet, chordal transfer, and replacement of anterior leaflet chordae by polytetrafluoroethylene sutures, and placement of annuloplasty ring. Group (2): Resect technique included 123 patients where the operation was done by resecting the prolapsed mid scallop of the posterior leaflet and placement of flexible annuloplasty ring.&#x0D; Results: There was no difference between both groups regarding gender. Patients in the Respect group were younger (37 (25th- 75th percentiles: 29- 44) vs. 54 (48- 60) years, P&lt;0.001). The minimally invasive approach was more commonly used in patients who had resection techniques (20 (26.32%) vs. 106 (86.18%); P&lt;0.001). Ischemic (99 (95- 106) vs. 79 (75- 82); P&lt;0.001) and cardiopulmonary bypass times (134.5 (130- 138.5) vs. 99 (97- 104) min; P&lt;0.001) were higher in the Respect group. Blood loss was more in the Resect group (370 (305- 390) vs. 550 (490- 600) ml; P&lt;0.001). There were no differences in the postoperative complications between groups. ICU stay was longer in patients in the Resect group (5 (5- 6) vs. 7 (6- 8) days; P&lt;0.001). Mitral valve gradient after 12 months was significantly higher in the Resect group (3 (3- 3.5) vs. 4 (3- 5) mmHg; P&lt;0.001). Mitral valve reoperation was required more in patients in the Respect group (5 (6.58%) vs. 1 (0.81%); P= 0.03).&#x0D; Conclusions: Both Respect and resect techniques for mitral valve repair had comparable outcomes and durability. The repair technique should be tailored according to the mitral valve pathology.

Identification and Characterization of Circulating MicroRNAs as Novel Biomarkers in Dogs With Heart Diseases.

Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases.Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis.Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.

TRPV1 Receptor Identification in Bovine and Canine Mitral Valvular Interstitial Cells.

Myxomatous mitral valve degeneration (MMVD) is the most common acquired cardiac disease in canine species, and valvular interstitial cells (VICs) are considered the main responsible for the development of this pathology. The scientific interest is focused on isolating and characterizing these cells. The aims of the present study were to verify a novel VICs mechanical isolation method and to characterize isolated cells using immunocytochemistry and immunofluorescence, with parallel histological and immunohistochemistry assays on bovine and canine healthy and MMVD mitral valves. Antibodies against vimentin (VIM), smooth muscle actin (SMA), von Willebrand (vW) factor, Transforming Growth Factor (TGF) β1, and Transient Receptor Potential Vanilloid 1 (TRPV1) were used. The isolation method was considered reliable and able to isolate only VICs. The different assays demonstrated a different expression of SMA in healthy and MMVD mitral valves, and TRPV1 was isolated for the first time from bovine and canine VICs and the correspondent mitral valve leaflets. The novelties of the present study are the new isolation method, that may allow correlations between laboratory and clinical conditions, and the identification of TRPV1, which will lead to further investigations to understand its function and possible role in the etiology of MMVD and to the design of new therapeutic strategies.

Congestive heart failures caused by myxomatous mitral valve degeneration in a Siberian tiger

A 19-year-old male Siberian tiger was presented with inappetence and paralysis of hind limbs. In a computed tomography (CT) scan, intervertebral disk disease at L3–L4 was detected. Cardiac arrest occurred during the surgery. At autopsy, myxomatous mitral valve degeneration (MMVD) and eccentric hypertrophy of the left heart were noted. The diagnosis was congestive heart failure caused by MMVD. Microscopically, myocardial and pulmonary fibrosis were observed in addition to the disintegration of the fibrosa layer and accumulation of glycosaminoglycans and proteoglycans in the spongiosa layer of the mitral valve. This is the first case of congestive heart failure with MMVD in a Siberian tiger.

Expression Profile of Circulating MicroRNAs in Dogs With Cardiac Hypertrophy: A Pilot Study.

This study aimed to identify the expression profile of circulating microRNAs in dogs with eccentric or concentric cardiac hypertrophy. A total of 291 microRNAs in serum samples of five dogs with myxomatous mitral valve degeneration (MMVD) and five dogs with pulmonic stenosis (PS) were compared with those of five healthy dogs using microarray analysis. Results of microarray analysis revealed up-regulation of cfa-miR-130b [fold change (FC) = 2.13, p = 0.014), down-regulation of cfa-miR-375 (FC = 1.51, p = 0.014), cfa-miR-425 (FC = 2.56, p = 0.045), cfa-miR-30d (FC = 3.02, p = 0.047), cfa-miR-151 (FC = 1.89, p = 0.023), cfa-miR-19b (FC = 3.01, p = 0.008), and cfa-let-7g (FC = 2.53, p = 0.015) in MMVD group which showed eccentric cardiac hypertrophy, up-regulation of cfa-miR-346 (FC = 2.74, p = 0.032), down-regulation of cfa-miR-505 (FC = 1.56, p = 0.016) in PS group which showed concentric cardiac hypertrophy, and down-regulation of cfa-miR-30c (FC = 3.45, p = 0.013 in MMVD group; FC = 3.31, p = 0.014 in PS group) and cfa-let-7b (FC = 11.42, p = 0.049 in MMVD group; FC = 5.88, p = 0.01 in PS group) in both MMVD and PS groups. In addition, the unsupervised hierarchical clustering of differentially expressed microRNAs in each group resulted in complete separation of healthy dogs from dogs with heart diseases. Therefore, eleven microRNAs among 291 microRNAs were identified as differentially expressed circulating microRNAs related to MMVD or PS in dogs. This pilot study demonstrates that the microRNAs identified in this study could be possible candidates for novel biomarker or therapeutic target related to cardiac hypertrophy in dogs.