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Background: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. Methods: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. Results: The new method moderately correlated with LA:Ao (r = 0.56–0.66) in all groups. The diagnostic accuracy (72–74%) of the subjective assessment and the new method showed no difference. Conclusions: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation.

The purpose of this study was to explore the pathomechanism of human myxomatous valve degeneration by investigating changes in the phenotype of valvular cells, the metabolism of the extracellular matrix and their mechanical properties. Mitral valve specimens were harvested from patients who had undergone valve replacement, and divided into two groups: patients with a myxomatous mitral valve and a control group. Histological investigation showed that the morphology of the extracellular matrix was looser and less coordinated in myxomatous valves than in controls. α-SMA (α-smooth muscle actin) and Vimentin were positive and DNA (deoxyribonucleic acid) assay of leaflets and expression of SMemb (embryonic smooth muscle myosin heavy chain), MMP-13 (matrix Metalloproteinases-13), MMP-1 mRNA (messenger Ribonucleic Acid) of the myxomatous valves were increased while the hydroxyproline content, expression of TIMP-1 (tissue inhibitor of metalloproteinase-1) mRNA and mechanical properties were decreased compared with controls. Compared to the quiescent interstitial cells in non-myxomatous valves, interstitial cells in myxomatous valves exhibit myofibroblast activation and express excessive levels of matrix metalloproteinases. The balance between MMP/TIMP was disrupted. We conclude that overactivation of VICs (Valvular interstitial cells) and the imbalance of MMP/TIMP could be important features of the pathomechanism of myxomatous mitral valve degeneration.

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.

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.

BACKGROUND: Myxomatous mitral valve degeneration is a common cause of mitral regurgitation and is often associated with mitral valve prolapse. With no known targets to pharmacologically treat mitral valve prolapse, surgery is often the only treatment option. Recently, radiofrequency ablation has been proposed as a percutaneous alternative to surgical resection for the reduction of mitral valve leaflet area. OBJECTIVE: Using an in vitro model of porcine mitral valve anterior leaflet enlargement following enzymatic digestion, we sought to investigate mechanisms by which radiofrequency ablation alters the geometry, microstructural organization, and mechanical properties of healthy and digested leaflets. METHODS: Paired measurements before and after ablation revealed the impact of radiofrequency ablation on leaflet properties. Multiphoton imaging was used to characterize changes in the structure and organization of the valvular extracellular matrix; planar biaxial mechanical testing and constitutive modeling were used to estimate mechanical properties of healthy and digested leaflets. RESULTS: Enzymatic digestion increased leaflet area and thickness to a similar extent as clinical mitral valve disease. Radiofrequency ablation altered extracellular matrix alignment and reduced the area of digested leaflets to that of control. Additionally, enzymatic digestion resulted in fiber alignment and reorientation toward the radial direction, causing increased forces during ablation and a structural stiffening which was improved by radiofrequency ablation. CONCLUSION: Radiofrequency ablation induces radial extracellular matrix alignment and effectively reduces the area of enlarged mitral valve leaflets. Hence, this technique may be a therapeutic approach for myxomatous mitral valve disease and is thus an avenue for future study.

Background: Antioxidants located in both the hydrophilic and lipophilic compartments of plasma act as a defence system against reactive oxygen species (ROS). . Excessive production of ROS during anaesthesia affects the antioxidant capacity of plasma and may result in oxidative stress. The aim of this study was to evaluate the antioxidant capacity of lipid- (ACL) and water-soluble (ACW) antioxidants in client-owned dogs diagnosed with periodontal disease and early-stage myxomatous mitral valve degeneration (MMVD) and anaesthetised for a dental procedure with propofol and sevoflurane or with propofol only. Results: Dogs with MMVD were anaesthetised with propofol and sevoflurane (MMVD/PS, n = 8) or with propofol only (MMVD/P, n = 10). Dogs with no evidence of MMVD (PS, n = 12) were anaesthetised with propofol and sevoflurane. Blood samples for determination of ACL and ACW were collected before and 5 minutes, 60 minutes and 6 hours after induction to anaesthesia. In dogs with MMVD and anaesthetised with propofol and sevoflurane, ACL was significantly higher at all sampling times when compared to control dogs. Compared to basal values, only anaesthesia maintained with propofol significantly increased ACL at 60 minutes in dogs with MMVD. In dogs with MMVD and anaesthetised with propofol, ACW increased after induction to anaesthesia and remained elevated up to 6 hours after anaesthesia. Compared to basal values, anaesthesia maintained with sevoflurane significantly increased ACW only at 60 minutes in both dogs with and without MMVD.The only difference between propofol and propofol/sevoflurane anaesthesia in dogs with MMVD was significantly higher ACW at 60 minutes after induction to anaesthesia in the propofol group. Conclusions: Regarding antioxidant capacity, propofol could be a better choice than sevoflurane for anaesthesia of dogs with early-stage MMVD, although further studies are necessary to clarify the advantage of this antioxidant capacity.

Relevance: Congestive heart failure in dogs is an urgent problem for Doctor of Modern Veterinary cardiology. Endocardiosis, or myxomatous mitral valve degeneration, is the most common acquired heart disease of dogs that has a potential adverse outcome. Accurate and timely diagnosis for this cardiopathology in dogs, and also effective monitoring of the progression of congestive heart failure syndrome are the most important problems of veterinary medicine. Purpose of research: To study the commitment of owners whose dogs with mitral valve endocardiosis to assess the respiratory rate of their pets during sleep and its impact on the survival of sick animals. Materials and methods. A prospective study of the survival rate of 181 dogs with mitral valve endocardiosis, complicated by congestive heart failure syndrome. Results: It was found that the degree of owners' commitment to assess the respiratory rate during sleep has a significant impact on the survival of dogs with mitral valve endocardiosis. The median life expectancy of sick dogs whose owners had a high commitment to monitoring respiratory function was significantly high. The survival time of sick dogs whose owners showed high adherence to the test was on average 604.8±53.1 days (variation from 0 to 1378; median – 452 days). In sick animals whose owners showed low adherence to assess the respiratory rate, the life expectancy was significantly low and averaged 279.9±28.9 days (variation from 0 to 1156; median – 122 days). In the Mann-Whitney test, this difference was found to be significant (p

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering.

There is limited information on long-term outcomes of mitral valve repair for mitral regurgitation (MR) caused by different degrees of myxomatous degeneration. The aim of this study was to compare the surgical results of patients with advanced and mild/moderate myxomatous mitral valve degeneration (MVD). We identified 130 patients (25 advanced and 105 mild/moderate MVD patients) who underwent mitral valve repair for MR and were pathologically diagnosed as myxomatous degeneration. Follow-up was 100% complete (mean length, 5.1 ± 1.8 years). Survival differed significantly between the advanced and mild/moderate MVD groups (76.0 ± 9.7% versus 95.0 ± 5.4% at 8 years, P < 0.001). The univariate predictors of mortality were advanced myxomatous degeneration, recurrent MR, and early series (surgeries before 2011). The mild/moderate MVD group had higher freedom from a moderate or severe MR rate compared with the advanced MVD group (77.4 ± 4.5% versus 50.5 ± 10.2% at 7 years, P = 0.003). Multivariable Cox analysis revealed advanced myxomatous degeneration and residual MR as independent predictors of recurrent moderate or severe MR. A total of 25 patients (19.2%) had persistent atrial fibrillation (AF) after repair. In multivariate analysis, advanced myxomatous degeneration was found to be an independent predictor of postoperative persistent AF.In conclusion, the long-term outcomes of mitral valve repair in patients with advanced MVD are poorer than in those with mild/moderate MVD. Advanced myxomatous degeneration is an independent predictor of recurrent moderate or severe MR and postoperative persistent AF in MVD patients performing repair, which deserves more attention before and after surgery.

The aim of this study was to investigate the effects of total intravenous anaesthesia with propofol and anaesthesia induced with propofol and maintained with sevoflurane on oxidative stress parameters in dogs with early-stage myxomatous mitral valve degeneration (MMVD). Sixteen client-owned dogs with early stage MMVD that required periodontal treatment were included in the study. After induction with propofol, anaesthesia was maintained with propofol (group P) or sevoflurane (group PS). Blood samples for determination of vitamin E, superoxide dismutase, glutathione peroxidase and malondialdehyde were collected before premedication, 5 and 60 minutes and 6 hours after induction to anaesthesia. There were no significant differences between groups in any of the oxidative stress parameters at each sampling time. Compared to basal values, vitamin E concentration decreased significantly during anaesthesia in both groups and glutathione peroxidase activity increased 60 minutes after induction to anaesthesia in PS group. Anaesthesia with propofol or with propofol and sevoflurane did not have any significant impact on oxidative stress parameters in dogs with early stage MMVD. In terms of oxidative stress, both protocols may be equally safely used in dogs with early stage MMVD.

OBJECTIVE To characterize expression profiles of circulating microRNAs via genome-wide sequencing for dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve degeneration (MMVD). ANIMALS 9 healthy client-owned dogs and 8 age-matched client-owned dogs with CHF secondary to MMVD. PROCEDURES Blood samples were collected before administering cardiac medications for the management of CHF. Isolated microRNAs from plasma were classified into microRNA libraries and subjected to next-generation sequencing (NGS) for genome-wide sequencing analysis and quantification of circulating microRNAs. 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. RESULTS 326 microRNAs were identified with NGS analysis. Hierarchical analysis revealed distinct expression patterns of circulating microRNAs between healthy dogs and dogs with CHF. Results of qRT-PCR assays confirmed upregulation of 4 microRNAs (miR-133, miR-1, miR-let-7e, and miR-125) and downregulation of 4 selected microRNAs (miR-30c, miR-128, miR-142, and miR-423). Results of qRT-PCR assays were highly correlated with NGS data and supported the specificity of circulating microRNA expression profiles in dogs with CHF secondary to MMVD. CONCLUSIONS AND CLINICAL RELEVANCE These results suggested that circulating microRNA expression patterns were unique and could serve as molecular biomarkers of CHF in dogs with MMVD.

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here.

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.

Myxomatous mitral valve degeneration (MMVD) causes an imbalance of sympathovagal activity resulted in poor cardiac outcomes. Phosphodiesterase-5 inhibitors have been revealed cardioprotective effect in patients with heart diseases. This study aimed to 1) compare the heart rate variability (HRV) between asymptomatic MMVD and healthy dogs and 2) assess long-term effects of sildenafil and enalapril on time- and frequency-domains analyzes. Thirty-four dogs with MMVD stage B1 or B2 and thirteen healthy dogs were recruited into the study. MMVD dogs were divided into 3 subgroups: control (n=13), sildenafil (n=12) and enalapril (n=9). HRV was analyzed from 1-hr Holter recording at baseline (D0) in all dogs and at 30, 90 and 180 days after treatment. The results showed that MMVD dogs had significant higher heart rate (HR), systemic blood pressures, the ratio of low to high frequency (LF/HF) and had significant decreased standard deviation of all normal to normal RR intervals (SDNN) and the percentage of the number of normal-to-normal sinus RR intervals with differences >50 msec computed over the entire recording (pNN50) when compared with healthy dogs (P

Sildenafil is a selective phosphodiesterase-5 inhibitor that has been demonstrated to delay ventricular remodeling in humans and experimental animals. The aim of this prospective study was to assess the chronic effects of sildenafil administration on echocardiographic indices and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in dogs with naturally occurring, asymptomatic myxomatous mitral valve degeneration. Thirty client-owned dogs with ACVIM class B1 or B2 were enrolled. Dogs were randomly assigned to treatment (sildenafil 1–3 mg/kg, PO, BID for 180 days) or control groups. A total of 12 dogs completed the 180 days trial in the sildenafil group, whereas 10 dogs remained in control group. When comparing the difference from baseline values obtained over time between groups, the stroke volume (SV) at day 30 was significantly higher in the sildenafil group (P=0.038). The LA/Ao and the MR jet area were significantly lower beginning at day 30 (only MR jet area; P=0.006), day 90 (P=0.006 and P=0.027, respectively) and day 180 (P=0.029 and P=0.032, respectively). The 2D-LA was significantly lower at day 90 when compared with control group (P=0.028). The differences of NTproBNP from baseline were significantly lower when compared with control group at the same timepoint (D90, P=0.017 and D180, P=0.013). In conclusion, this study suggested that long-term treatment with sildenafil prevented aggravation of disease progression as suggested by several echocardiographic indices (i.e. SV, LA/Ao, MR jet area, 2D-LA) and reduced NTproBNP level at the indicated timepoints in dogs with asymptomatic mitral valve degeneration.

Pimobendan is a positive inotrope and balanced vasodilator via its actions as a calcium sensitiser and phosphodiesterase III inhibitor, respectively.1 There is strong evidence for its use in the treatment of dogs with congestive heart failure (CHF), with multiple clinical trials demonstrating a resultant increase in survival time.2-5 However, the use of pimobendan for treatment of heart disease in people has been associated with increased risk of arrhythmias.6 This effect is attributed to the racemic nature of pimobendan resulting in D and L chiral enantiomers, with the L-optical isomer having a significantly greater calcium sensitising effect.7-9 There is limited data available regarding any effect of treatment with pimobendan on the risk of arrhythmias in dogs. The aim of this article is to analyse the available data to determine whether evidenced-based conclusions can be drawn. In [dogs with cardiac disease] does treatment with [pimobendan] compared to [alternative treatments OR placebo] lead to [increased risk of arrhythmias]? The search strategy is available as a supplement to this article on Vet Record’s website at http://veterinaryrecord.bmj.com/content/183/22/693 ### Supplementary file 1 [vetreck5167-SP1.docx] Search last performed: 31 May, 2018 Paper 1: Effect of pimobendan on the incidence of arrhythmias in small breed dogs with myxomatous mitral valve degeneration (MMVD)10 Patient group: Eight client-owned small breed dogs (

Valvular involvement in Lyme disease is rare. Confirmation of Borrelia species as the causative agent with polymerase chain reaction was done in a few cases in Europe and the United States. We describe a case of mitral regurgitation with a preoperative diagnosis of myxomatous mitral valve degeneration. During surgery, the surgeon suspected infective rather than degenerative etiology; the results of tissue cultures were negative. However, universal bacterial polymerase chain reaction on explanted valve tissue detected Borrelia burgdorferi DNA. If a surgeon suspects infective endocarditis at the time surgery, appropriate specimens should be sent for histopathologic analysis, culture, and polymerase chain reaction assay.

Background The etiology of myxomatous mitral valve degeneration (MVD) is not fully understood and may depend on time or environmental factors for which the interaction of infectious agents has not been documented. The purpose of the study is to analyze the effect of Mycoplasma pneumoniae (Mp), Chlamydophila pneumoniae (Cp) and Borrelia burgdorferi (Bb) on myxomatous mitral valve degeneration pathogenesis and establish whether increased in inflammation and collagen degradation in myxomatous mitral valve degeneration etiopathogenesis. Methods An immunohistochemical test was performed to detect the inflammatory cells (CD20, CD45, CD68) and Mp, Bb and MMP9 antigens in two groups. The in situ hybridization was performed to detect Chlamydophila pneumoniae and the bacteria study was performed using transmission electron microscopy. Group 1 (n = 20), surgical specimen composed by myxomatous mitral valve degeneration, and group 2 (n = 20), autopsy specimen composed by normal mitral valve. The data were analyzed using SigmaStat version 20 (SPSS Inc., Chicago, IL, USA). The groups were compared using Student’s t test, Mann-Whitney test. A correlation analysis was performed using Spearman’s correlation test. P values lower than 0.05 were considered statistically significant. Results By immunohistochemistry, there was a higher inflammatory cells/mm2 for CD20 and CD45 in group 1, and CD68 in group 2. Higher number of Mp and Cp antigens was observed in group 1 and more Bb antigens was detected in group 2. The group 1 exhibited a positive correlation between the Bb and MVD percentage, between CD45 and Mp, and between MMP9 with Mp. These correlations were not observed in the group 2. Electron microscopy revealed the presence of structures compatible with microorganisms that feature Borrelia and Mycoplasma characteristics. Conclusions The presence of infectious agents, inflammatory cells and collagenases in mitral valves appear to contribute to the pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with myxomatous mitral valve degeneration. Despite of low percentage of Borrelia burgdorferi in MD group, this agent was correlated with myxomatous degeneration and this may occour due synergistic actions between these infectious agents likely contribute to collagen degradation. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2387-8) contains supplementary material, which is available to authorized users.

Mitral valve repair for mitral regurgitation (MR) is currently recommended based on the degree of MR and left ventricular (LV) function. The present study examines predictors of reverse remodeling after repair for degenerative disease. We retrospectively identified 439 patients who underwent repair for myxomatous mitral valve degeneration and had both pre- and postoperative echocardiographic data available. Patients were categorized based on left atrial (LA) diameter and LV diameter standards of the American Society of Echocardiography. The outcome of interest was the degree of reverse remodeling on all heart dimensions at follow-up. Mean age was 57 ± 12 years, and 37% of patients were women. Mean preoperative LV end-diastolic diameter was 5.8 ± 0.7 cm, LV end-systolic diameter 3.5 ± 0.6 cm, LA 4.7 ± 0.7 cm, and median ejection fraction 60%. Median observation time was 81 months, and time to postoperative echocardiography was 38 months. Overall, 95% of patients had normal LV diastolic dimensions postoperatively, 93% normal LV systolic dimensions, and 37% normal LA dimensions. A Cox regression analysis showed that moderate (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.4) or severe preoperative LA dilatation (OR 2.7, 95% CI 1.7 to 4.4), abnormal preoperative LV end-systolic dimensions (OR 1.3, 95% CI 1.1 to 1.5), and age in years (OR 1.02, 95% CI 1.01 to 1.03) were predictive of less reverse remodeling on follow-up. In conclusion, preoperative LV end-systolic dimensions and LA dilatation substantially affect the likelihood of successful LA remodeling and normalization of all heart dimensions after mitral valve repair for MR. These findings support early operation for MR before the increase in heart dimensions is nonreversible.

The utility of cells cultured from the mitral valve as models of myxomatous diseases needs to be properly validated. In this study valve interstitial cells (VICs) and valve endothelial cells (VECs) were cultured from normal and diseased canine mitral valves in 2% (v/v) or 10% FBS media, in the presence of TGFβ1, 2 and 3, the TGF RI kinase inhibitor SB431542 and TGFβ neutralising antibodies, 5HT and the 5HT2RB antagonist LY272015. Cultures were examined by morphology, transcriptomic profiling, protein expression of the cell specific markers αSMA and SM22α (VICs), and CD31 (VECs), deposition of proteoglycans (PG), the PG versican, and the TGFβs themselves. VECs derived from normal valves were CD31+/αSMA-, but those from diseased valves were αSMA+, indicating endothelial-to-mesenchymal (EndoMT) transition had occurred. The TGFβs induced EndoMT in normal VECs, and this was abolished by SB431542, with significant changes in αSMA, CD31 and HAS2 expression (P

[This corrects the article DOI: 10.3389/fvets.2021.652224.]., (Copyright © 2021 Frontiers Production Office.)

Left atrial tear is an infrequent sequela of severe mitral regurgitation due to myxomatous mitral valve degeneration. Interatrial septal tear due to mitral regurgitation causing a left-to-right shunt is uncommon. Right to left shunting secondary to acute interatrial septal tear is very rarely reported in the human literature, and has not been reported in the veterinary literature in a dog. This case describes the clinical, radiographic, echocardiographic, gross pathologic, and histopathologic features of a dog presented in acute respiratory distress secondary to acute onset right to left shunting through the interatrial septum. This was later documented to be due to a tear in the septum secondary to tricuspid regurgitation and pulmonary hypertension. The presence of an acquired right to left shunting atrial septal defect is of clinical and prognostic significance, and should be considered in cases of acute respiratory distress.

Background Cough in the geriatric small breed dog with myxomatous mitral valve degeneration (MMVD), a large left atrium, and absence of heart failure often is attributed to compression of the left mainstem bronchus by the left atrium. Studies investigating this syndrome are lacking in dogs. Hypothesis Airway collapse is independent of left atrial enlargement. Animals A total of 16 dogs presenting with chronic cough in the absence of congestive heart failure. Group 1 dogs (n = 10) had moderate-to-severe left atrial enlargement based on an echocardiographically calculated left atrial:aortic surface area [LA:Ao(a)] > 6. Group 2 dogs (n = 6) had no to mild left atrial enlargement [LA:Ao(a) ≤ 6]. Methods Dogs were prospectively evaluated. CBC, biochemistry, urinalysis, cervical and thoracic radiographs, fluoroscopy, echocardiography, and bronchoscopy were performed. Bronchoscopic abnormalities were compared between groups using Fisher's Exact Test. P 50% was observed in multiple bronchi with no difference between groups. All dogs had inflammation on airway cytology with respiratory infection in 1 dog in group 2. Left atrial size was interpreted radiographically as enlarged in 9 of 10 group 1 dog and in 2 of 6 group 2 dogs. VHS was above normal in both groups of dogs regardless of echocardiographic evidence of cardiomegaly. Conclusions Results failed to identify an association between left atrial enlargement and airway collapse in dogs with MMVD, but did suggest that airway inflammation is common in dogs with airway collapse.

An increased tracheal bifurcation angle on the dorsoventral projection is described as a sign of left atrium enlargement in dogs, with a normal range of 60-90 degrees reported. However in people, this angle is a poor indicator of left atrial size. Our purpose was to evaluate the value of the tracheal bifurcation angle for differentiating normal from enlarged left atrium in dogs. Dorsoventral radiographs and echocardiograms of 33 healthy and 73 dogs with confirmed degenerative myxomatous mitral valve disease were evaluated. Left atrial size was classified according to the echocardiographic left atrium to aorta ratio, as normal, mildly, moderately, or severely enlarged. Independent samples t-tests were used to compare the bifurcation angle between groups. A significant difference was observed between the angle of dogs with normal left atrium (68.1 +/- 8.5 degrees, range: 51.3-92.4 degrees) and dogs with enlarged left atrium (75.8 +/- 8.2 degrees, range: 57.3-91.7 degrees). A significant difference was also noted between the angle of normal dogs and those with moderate (75.5 +/- 6.8 degrees, range: 62.8-88.7 degrees) and severe (80.4 +/- 7.7 degrees, range: 64.7-91.7 degrees) left atrial enlargement, as well as between dogs with mild (70.7 +/- 7.2 degrees, range: 57.3-89.9 degrees) and severe enlargement. Using two discriminators, 85.1 degrees and 76.6 degrees, the bifurcation angle had a specificity of 92.6% and 88.9%, respectively, for identifying left atrial enlargement, and a sensitivity of 15.4% and 40.4%. Although significant differences were observed between dogs with normal and increased left atrial size, the large degree of overlap in the range of bifurcation angles and its poor sensitivity make the measurement of this angle of little value for diagnosing left atrial enlargement.

Objective To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD). Animals, materials and methods Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery. Results Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09). Conclusions Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.

The objective of this study was to correlate defined pathological features with clinical findings in dogs with naturally occurring congestive heart failure (CHF). Fifty-eight dogs with CHF were examined clinically and using echocardiography and electrocardiography. Detailed cardiac post-mortem examination was used to assess intra-myocardial arterial narrowing, myocardial fibrosis and atrophy and myxomatous mitral valve degeneration (MMVD). Arterial narrowing significantly correlated with fibrosis (P0.0001) and with fractional shortening, an indicator of systolic function (P=0.002). The grade of fibrosis was associated with shorter survival time (P=0.002), and the papillary muscle fibrosis score tended to correlate with proximal isovelocity surface area radius (P=0.03). Data from this study lend support to the hypothesis that naturally occurring canine CHF is affected by several factors such as MMVD, myocardial atrophy and fibrosis, and by arteriosclerosis. Further, more extensive research will be required to establish cause-effect relationships between these cardiac lesions and the pathophysiology of CHF in dogs.

Small-breed dogs (n = 168; weight ＜ 15 kg) diagnosed with myxomatous mitral valve degeneration based on a routine clinical examination, radiology, electrocardiography, and echocardiography at the Seoul National University Veterinary Medical Teaching Hospital were included in this study. Survival periods were determined, and there were significant differences in survival rates among the three International Small Animal Cardiac Health Council classes. The mean follow-up period was 14.3 ± 12.1 months. Univariate analysis revealed that dyspnea, pulmonary edema, and vertebral heart score were significantly associated with survival time (p ＜ 0.05). Additionally, age, left atrial-to-aortic root ratio, ejection fraction, and left ventricular end diastolic volume were associated with an increased risk of death (p ＜ 0.1), while body weight, body condition score, systolic blood pressure, arrhythmia, syncope, fractional shortening, and end systolic volume were not associated with an increased risk of death. These results suggest that among the assessed variables dyspnea, pulmonary edema, and vertebral heart score could be useful prognostic factors for providing patient information to owners.

Background Myxomatous degeneration of the mitral valve is a common pathological finding in mitral valve surgery and the most common reason for severe mitral valve regurgitation. Considering the importance of right ventricular remodeling and global function after mitral valve surgery we tried to elucidate a possible association of myxomatous mitral valve and impairment of right atrial and ventricular function, which might have an impact on global ventricular performance after mitral valve surgery. Methods Right atrial tissue was harvested from 47 patients undergoing mitral valve surgery. We took the trabeculae from the right auricle, which was resected at the right auricle for implementation of extracorporal circulation. The tissue was skinned and prepared in a 24 h-lasting procedure to create small fibers for hinging them in the "muscle machine", an experimental set-up, created for pCa-force measurements. Results Patients without myxomatous mitral valve developed significantly more force (4.0 mN ± 0.8 mN) at the highest step of calcium concentration compared to 2.7 mN ± 0.4 mN in group of patients with myxomatous valve degeneration (p 0.03). Calcium sensitivity in the myxomatous valve group was at pCa 6.0 and in the non-myxomatous group at pCa 5. Furthermore we observed a significant difference in ejection fraction (EF) among the groups: 49% in the non-myxomatous group versus 57% in the myxomatous group (p 0.03). In the non-myxomatous group 5 patients had diastolic dysfunction grade I-II (22,7%), in group I 10 patients (40%). This was also significant (p 0.04). Conclusions Patients with myxomatous mitral valve degeneration seem to have reduced force capacities. Calcium sensitivity is higher compared to the non-myxomatous group, which might be a compensatory mechanism to cover the physiological demand. Furthermore we suggest a higher incidence of diastolic dysfunction in patients with myxomatous mitral valve degeneration, which might have an impact on ventricular remodeling after mitral valve surgery.

A doença Mixomatosa Valvular Mitral (DMVM) é a doença cardíaca adquirida mais frequentemente diagnosticada em cães adultos. Uma vez que o curso desta doença é algo imprevisível, é de grande importância clínica conseguir prever a sua progressão e a longevidade de cães afectados. Com este estudo pretendeu-se estimar o tempo de sobrevivência e o tempo até desenvolvimento de insuficiência cardíaca congestiva (ICC) numa amostra heterogenia de cães, em diferentes estadios da doença. Adicionalmente foi avaliado o valor prognóstico de determinados parâmetros ecocardiográficos em relação à sobrevida. Foram utilizados historiais clínicos de 542 cães com DMVM, diagnosticados através de ecocardiografia no Hospital Veterinário do Porto. A informação relativa à evolução clínica destes cães foi obtida através de entrevista telefónica. Cento e vinte e seis de 241 (52.7%) cães morreram durante o período de observação (20.59 meses). O tempo médio de sobrevivência quando consideradas todas as causas de morte foi de 19.87 meses. Quando consideradas apenas as mortes devido à doença, o tempo médio de sobrevivência foi de 18.73 meses. O aumento da Emax (p= 0.049), do ETdec, (p= 0.026) e do EDDI (p= 0.008) demonstraram influenciar negativamente o tempo de sobrevivência destes cães. Quinze dos 150 (10%) cães assintomáticos reavaliados, desenvolveram ICC durante o período de observação. O tempo médio até desenvolvimento de ICC foi de 19.9 meses. A DMVM ligeira a moderada representa uma doença relativamente benigna em cães. A utilização de parâmetros ecocardiográficos poderá auxiliar na identificação de cães com um pior prognóstico., Myxomatous Mitral Valve Disease (MMVD) is the most commonly diagnosed acquired heart disease in adult dogs. Since the course of this disease is quite unpredictable, it is of clinical importance to be able to predict its progression and longevity of affected dogs. The aims of this study were to evaluate survival time and time until development of congestive heart failure (CHF) in a heterogeneous group of dogs, at varying stages of the disease. In addition, the prognostic value of certain echocardiographic parameters on survival was evaluated. Medical records of 542 dogs with MMVD, diagnosed by echocardiography at Hospital Veterinário do Porto, were reviewed. The information regarding long-term outcome of these dogs was obtained through telephone interviews. One hundred and twenty six of 241 (52.7%) dogs died during the observation period (20.59 months). The mean survival time, when all causes of death were considered, was 19.87 months. When only deaths due to the disease were considered, the mean survival time was 18.73 months. An increase in Emax (p= 0.049), in ETdec (p= 0.026) and in EDDI (p= 0.008), showed a negative effect on survival time of these dogs. Fifteen of the 150 (10%) asymptomatic dogs re-examined, developed CHF during the observation period. The mean time until development of CHF was 19.9 months. Mild to moderate MMVD represents a relatively benign disease in dogs. The use of echocardiographic parameters can help identify dogs with a worse prognosis., Orientação : Luís Lima Lobo

Na Doença Degenerativa Mixomatosa da Válvula Mitral (DDMVM) o aumento do átrio esquerdo (AE) marca o início da doença. A ecocardiografia, através do ratio AE/Aorta (AO) identifica e quantifica este aumento atrial e permite a classificação dos pacientes em B2. A radiografia permite apenas auxiliar no diagnóstico e monitorização de pacientes B2. No entanto a utilização do índice cardíaco vertebral (ICV ou Vertebral Heart Score (ICV)) atrial radiográfico permite quantificar o aumento do átrio esquerdo indicativo da presença de DDMVM. A presente dissertação pretendeu avaliar e explorar o ICV atrial em cães e conhecer a sua correlação com o a técnica de referência AE/Ao. Assim os objetivos propostos foram i) padronizar o ICV atrial e comparar os valores de ICV atrial entre animais saudáveis e doentes B2; e ii) avaliar a correlação entre o ICV atrial e o ratio AE/Ao. Para tal foi estudada uma amostra de 33 cães sem diagnóstico de patologia cardíaca (grupo controlo) e de 22 cães diagnosticados com DDMVM em estádio B2, de acordo com a classificação American College of Veterinary Internal Medicine (ACVIM). Os valores médios do ICV atrial do grupo controlo foram semelhantes aos valores médios do grupo de pacientes B2. Entre o ICV atrial e o ratio AE/Ao a correlação foi moderada, com uma dependência não linear. Apesar de se tratar de um método simples simples de realizar e ao alcance da maioria das clínicas veterinárias, este método não faz parte do exame cardiovascular de rotina dos cardiologistas veterinário. Os resultados obtidos no presente trabalho sugerem que este método não aporta vantagem na classificação dos pacientes B2 e que a determinação do ICV atrial apresenta reduzida utilidade no diagnóstico de DDMVM., In Myxomatous Mitral Valve Degeneration MMVD the left atrium enlargement (LA) dictates the disease onset and outcome. The echocardiography, by means of the left atrium aortic root ratio (LA/Ao) enables the identification and quantification the LA enlargement as well as the stanging B2 patients. Radiography usefulness is limited as it can only help the diagnosis and monitoring of the patients B2. Nevertheless, the use of the Left Atrium-Vertebral Heart Score (LA-ICV) allows the quantification of the LA enlargement, a predictor of MMVD. With this work we intended to explore the LA-ICV in dogs and to evaluate its correlation with the gold standart tecnique LA/Ao ratio. Therefore the aims were: i) the standarzation of the LA-ICV and the comparison of its values between healthy and B2; and ii) to acess the correlation between the LA-ICV and LA/Ao ratio. For this, we studied a sample of 33 dogs without cardiac disease diagnosis (the control group) and 22 dogs with MMVD in stage B2, according with the American College of Veterinary Internal Medicine (ACVIM) classification. In average, the values of the control group were similar to those of the B2 stage patients. The correlation between LA-ICV and LA/Ao ratio was moderated, with a non linear dependency. Despite being a simple and easy method to perform in most veterinary clinics, this method is not included in the routine cardiovascular procedures performed by the veterinary cardiologists. The results sugget that this method is not helpful for B2 patients classification and that LA-ICV was of little use for MMVD diagnosis., Orientação: Luís Lobo ; Co-orientação: Manuel Monzo