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Objective: To determine procedural feasibility, safety, and short-term efficacy in dogs with severe degenerative mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) with a canine-specific device. Design: Prospective, single-arm (uncontrolled), single-institution clinical feasibility study. Animals: Fifty client-owned dogs with severe degenerative MR operated over a 28-month period. Methods: TEER was performed using the canine mitral V-Clamp via a transapical approach using transesophageal echocardiographic and fluoroscopic guidance. Indices of MR severity were determined by echocardiography the day before and 2 to 3 days after the procedure. Results: Procedural feasibility was 96% based on delivery of at least one device in 48 of 50 dogs. There were no procedural deaths. Procedural safety was 96% based on survival to hospital discharge in 48 of 50 dogs. Euthanasia in 2 dogs prior to hospital discharge was due to damage of the mitral valve and worsened MR after the procedure. Device-related adverse event rate was 6.3% based on 3 events (single-leaflet device detachment, locking failure, locking failure with device embolization) in 59 implanted devices. All three events were nonfatal and successfully treated with a second device. Median regurgitant volume (mL/kg) decreased (p < 0.001) from 2.3 [1.9, 3.1] to 1.1 [0.3, 1.8]. Median effective regurgitant orifice area (cm2/m2) decreased (p < 0.001) from 0.60 [0.40, 0.80] to 0.25 [0.10, 0.50]. Conclusion and clinical importance: Initial feasibility results support continued development of TEER as a procedurally feasible, relatively low-risk, and low morbidity treatment for degenerative MR in dogs. Operator experience and case selection are likely to be important components of success of this technique. Evidence of short-term efficacy is promising but needs to be verified with longer-term follow up. [ABSTRACT FROM AUTHOR]

Myxomatous Mitral Valve Disease (MMVD) is a degenerative condition of the mitral valve where it weakens and causes regurgitation, eventually leading to cardiac remodeling. Jason, a seven-year-old male Shih Tzu weighing 7.5 kg, was presented with a persistent cough and exercise intolerance lasting over a month. A physical examination revealed a Grade II/VI heart murmur. Radiography and echocardiography were performed as part of the laboratory examinations. Radiography demonstrated cardiac remodeling, with a VHS of 10.3 viscerocranial, an intercostal space of 3, and a VLAS of 2.3. Echocardiography unveiled left atrial enlargement, mitral valve regurgitation, and a reduction in heart function. The dog was treated with Pimobendan (Cardisure® 10mg, Dechra, England) as an inodilatator at 0.25mg, Enalapril Maleate 0.5mg/kg (Tenace® 5mg, Combiphar, Indonesia), and furosemide (Farsix® 40mg, Fahrenheit, Indonesia) at 2 mg/kg via oral route twice a day over the course of seven days. Thereafter, the dose was reduced to 1.5 mg/kg PO twice a day for seven days, and eventually once a day for the remainder of the seven days. Following the three-week treatment, there was a significant reduction in the frequency and intensity of coughing.

Introduction: This study explored the potential efficacy and safety of therapy with mesenchymal stem cells (MSC) derived from gonadal tissue to address the early stage of myxomatous mitral valve disease (MMVD), the predominant cardiac condition in dogs. Methods: Sixteen dogs diagnosed with MMVD B1 were enrolled in this trial and assigned to either a control group (control group, n = 10) or a group that received MSC derived from gonadal tissue (treatment group, n = 6). In the treatment group, allogeneic MSC derived from gonadal tissue (1 × 106 cells/kg) were intravenously administered at monthly intervals for five or more sessions. Data were compared at baseline and at the endpoint 1-year intervals. The efficacy was assessed using echocardiography, thoracic radiography, NT-proBNP, and the duration from B1 diagnosis to B2 transition to evaluate its effect on MMVD stage progression. Safety was evaluated through physical examinations, blood tests, imaging studies, and monitoring of adverse events. Results: After 1 year of observation, the control group exhibited deteriorating echocardiographic parameters, whereas the treatment group displayed no substantial differences between baseline and endpoint measurements. Notably, a statistically significant disparity was noted in the left atrial diameter (p < 0.05) and E-wave velocity (p < 0.05) between the two groups, indicating a favorable impact of MSC derived from the gonadal tissue on left atrial pressure. Additionally, in contrast to the control group, the treatment group demonstrated delayed progression to MMVD stage B2, enabling them to prolong their disease duration without requiring cardiac medication (p = 0.038). In quality of life (QoL) metrics following MSC treatment, appetite showed a statistically significant improvement, increasing from 4 to 4.83 (p < 0.05). Discussion: Treatment with gonadal tissue-derived MSCs significantly delayed MMVD stage progression, highlighting the broad potential of MSC derived from gonadal tissue for treating complex veterinary conditions. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial volume (LAV) obtained using real-time three-dimensional echocardiography (RT3DE) is an independent predictor of postcapillary pulmonary hypertension (PH) in humans; however, no studies have investigated LAV obtained using RT3DE as a predictor of post-capillary PH in dogs with myxomatous mitral valve disease (MMVD). Therefore, we aimed to evaluate the clinical applicability of LAV obtained using RT3DE compared to that obtained using two-dimensional echocardiography (2DE) in dogs with MMVD, with or without PH. Methods: Medical records and echocardiographic images of 237 privately owned dogs with naturally occurring MMVD with or without PH were retrospectively reviewed. A total of 49 privately owned dogs with naturally occurring MMVD, with or without PH, were finally included (35 MMVD without PH, 14 MMVD with PH). The LAV and left ventricular volumes were obtained using 2DE and RT3DE. Echocardiographic parameters were analyzed to identify independent predictors of post-capillary PH. Results: We found that the left atrial and left ventricular volumes obtained using 2DE and RT3DE indexed to body weight and several 2DE-derived variables were univariately associated with post-capillary PH. Furthermore, multivariable logistic regression analysis revealed that the RT3DE minimum LAV indexed to body weight (LAVi min) was the only significant independent predictor of post-capillary PH (odds ratio, 12.86; 95% confidence interval [CI], 2.40--68.99; p = 0.003), with the highest area under the curve value of 0.86 (95% CI, 0.75-0.96; p < 0.001). Discussion: In conclusion, LAV indexed to body weight obtained using 2DE and RT3DE, can be a useful predictor of post-capillary PH in dogs with MMVD. In particular, the RT3DE LAVi min was observed to be the strongest predictor of post-capillary PH. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine procedural feasibility, safety, and short-term efficacy in dogs with severe degenerative mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) with a canine-specific device.DesignProspective, single-arm (uncontrolled), single-institution clinical feasibility study.AnimalsFifty client-owned dogs with severe degenerative MR operated over a 28-month period.MethodsTEER was performed using the canine mitral V-Clamp via a transapical approach using transesophageal echocardiographic and fluoroscopic guidance. Indices of MR severity were determined by echocardiography the day before and 2 to 3 days after the procedure.ResultsProcedural feasibility was 96% based on delivery of at least one device in 48 of 50 dogs. There were no procedural deaths. Procedural safety was 96% based on survival to hospital discharge in 48 of 50 dogs. Euthanasia in 2 dogs prior to hospital discharge was due to damage of the mitral valve and worsened MR after the procedure. Device-related adverse event rate was 6.3% based on 3 events (single-leaflet device detachment, locking failure, locking failure with device embolization) in 59 implanted devices. All three events were nonfatal and successfully treated with a second device. Median regurgitant volume (mL/kg) decreased (p

Background: Mitral valvuloplasty (MVP) is a surgical procedure for treating severe mitral regurgitation in dogs. Although MVP is considered highly invasive, the extent of myocardial injury, postoperative complications, and recovery has not been evaluated. Aim: This study examined the degree of MVP invasiveness, the extent of myocardial damage, postoperative complications, cardiomyocyte recovery, and timing of hospital discharge. Methods: Cardiac troponin I (cTnI) was used to investigate the myocardial damage caused by cardiac arrest associated with a surgical approach to the myocardium in 13 patients with MVP and 5 controls with patent ductus arteriosus who underwent similar anesthesia and thoracotomy. Results: The level of cTnI peaked 1 day after surgery and was significantly higher in the MVP group (median, 19.90 ng/mL) than in control group (median, 1.50 ng/mL P < 0.001). At day 7, the cTnI level was significantly higher in the MVP group (1.9 ng/mL) than in control group (0.1 ng/mL) (P < 0.001), and recovery to the preoperative level took 10 days in the MVP group but returned to the preoperative level at day 7 in control group. Although the mean arterial pressure of cardiopulmonary bypass at the time of use was 42.92 mmHg, the peak cTnI levels in the two patients who exhibited a temporary decrease of 20 mmHg or less (46.03 ng/mL) were significantly higher than in the other 11 patients (19.70 ng/mL) (P < 0.05). Preoperative cTnI levels were correlated with the severity of postoperative complications (P = 0.03, F = 0.71). Conclusion: The results showed that MVP caused temporary greater myocardial tissue damage than thoracotomy, but postoperative recovery was smoother. A high preoperative cTnI level requires relatively more careful postoperative management, and measuring the level of cTnI over time after surgery can provide information about the extent of myocardial damage and recovery from surgery and help determine the time of discharge. [Open Vet J 2024; 14(7.000): 1625-1633]

Background: Myxomatous mitral valve disease (MMVD) is prevalent in dogs. Specialized diagnostics (radiography, echocardiography) may be unavailable in some veterinary settings. Cardiac biomarkers offer potential alternatives. Aim: This study evaluated diagnostic value of N-terminal fragments of pro-brain natriuretic peptides (NT-proBNPs), atrial natriuretic peptides (ANPs), and cardiac troponin I (cTnI) levels in dogs with MMVD. Methods: 69 dogs with MMVD (asymptomatic and symptomatic) and 19 healthy controls were assessed. Biomarker levels were measured using commercial kit rapid tests. Results: Our results showed that the median NT-proBNP level in the symptomatic group was higher than those in the asymptomatic (P < 0.001) and control (P < 0.001) groups. Moreover, the median NT-proBNP level in the asymptomatic group was higher than that in the control group (P < 0.001). The cTnI level in the control group was lower than those in the asymptomatic (P = 0.039) and symptomatic (P = 0.001) groups. No statistically significant difference in the cTnI level was noted between the asymptomatic and symptomatic groups. The best cutoff value of the NT-proBNP level to differentiate the normal controls from dogs with MMVD with or without congestive heart failure was > 505.65 pmol/L (sensitivity, 76.8%; specificity, 89.5%; and area under the curve [AUC], 0.862). The suggested cutoff value of the NT-proBNP level to differentiate symptomatic MMVD from asymptomatic MMVD was >787.65 pmol/L (sensitivity, 78.38%; specificity, 72.55%; and AUC, 0.792). Conclusion: NT-proBNP and cTnI may serve as point-of-care tests for dyspneic dogs, aiding MMVD assessment where specialized diagnostics are limited. [Open Vet J 2024; 14(6.000): 1426-1441]

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

Abstract Background Differentiation of the subclinical phases of myxomatous mitral valve disease (MMVD) in dogs relies heavily on echocardiography. Focused cardiac ultrasonography (FCU) is a point‐of‐care technique that can assess heart size. Hypothesis/Objectives Veterinary students trained in FCU can differentiate dogs with subclinical MMVD based on left ventricular (LV) and left atrial (LA) dimensions. Animals Forty‐eight dogs with subclinical MMVD. Methods Veterinary students were trained to measure LV dimension and LA‐to‐aortic root dimension ratio (LA : Ao) using FCU. Dogs were categorized into 2 cohorts based on whether or not the LV normalized internal diastolic dimension was ≥1.7 and LA : Ao was ≥1.6. Agreement between FCU and echocardiographic studies performed by cardiologists was evaluated. Results One‐hundred and forty‐six FCU examinations were performed by 58 veterinary students on 48 dogs. Overall agreement between students and cardiologists was moderate (Fleiss' kappa, 0.54; 95% confidence interval [CI], 0.39‐0.69; P

OBJECTIVE: Cardioplegic solutions are indispensable for open-heart surgeries, including mitral valve repair (MVR), a potentially curative treatment for myxomatous mitral valve disease in dogs. However, procedural methodologies are not fully established, and complications are yet to be comprehensively understood. Cardioplegic solutions contain various substances to protect the myocardium under temporal cardiac arrest. Nevertheless, ventricular fibrillation (VF) occurs as a common complication after releasing the crossclamp. Based on these backgrounds, the search for optimal cardioplegic solutions in dogs undergoing MVR is an urgent issue. This study aims to evaluate the occurrence of VF in dogs treated with blood cardioplegia (BCP) versus crystalloid cardioplegia (CCP) during MVR. ANIMALS: A total of 251 client-owned dogs who underwent MVR from November 2015 to November 2017 were included. METHODS: We retrospectively assessed the relationship between VF and type of cardioplegia (CCP or BCP) based on surgical records, including VF incidence, transfusion use, crossclamp time, and echocardiographic measurements. RESULTS: Logistic regression analysis showed that the CCP group was associated with the occurrence of VF (OR, 2.378; CI, 1.133-4.992; P = .022). In addition, the CCP group was associated with transfusion use (OR, 2.586; CI, 1.232-5.428, P = .022). There was no difference between the groups for the pre- and postoperative echocardiographic measurements. CLINICAL RELEVANCE: The BCP group had a lower incidence of VF and less transfusion use than the CCP group. This finding indicates that BCP may be a superior cardioplegic technique for MVR in dogs. [ABSTRACT FROM AUTHOR]

Myxomatous mitral valve disease (MMVD) is a degenerative disease of the valve leaflets, causing left atrial dilatation and eccentric hypertrophy of the left ventricle by hemodynamic instability. Red cell distribution width (RDW) is a hematologic parameter that indicates the variation of red blood cell volume and size, reflecting anisocytosis. Human studies have found that anisocytosis is associated with poor prognosis in heart disease patients, and recent veterinary studies have also confirmed that the increase in RDW is associated with high mortality in MMVD patients. Medical records of 37 Maltese dogs with MMVD were retrospectively reviewed. When comparing RDW among the MMVD stage groups, there was a significant difference between stage B1, B2 and C. A significant and strong correlation between RDW and the left atrial-to-aortic ratio was identified. RDW was significantly correlated with the reticulocyte count independent of hematocrit, and the reticulocyte count exhibited a significant increase at stage C. This suggests that the congestive heart failure secondary to MMVD could be a contributory factor leading to an elevation in RDW. In conclusion, elevated RDW may associated with left atrial enlargement and progression of MMVD. [ABSTRACT FROM AUTHOR]

To echocardiographically evaluate a large number of apparently healthy Czechoslovakian wolfdogs (CWDs) to identify possible subclinical cardiac abnormalities and to generate reference intervals. One-hundred and seventeen apparently healthy client-owned CWDs. Standard two-dimensional, M-mode, and Doppler echocardiographic measurements were obtained on non-sedated, manually restrained standing dogs. Animals with no relevant echocardiographic abnormalities were used to generate reference intervals. Echocardiographic variables were compared between males and females and between dogs with and without mitral regurgitation (MR). Among the 117 CWDs, 103 dogs were used to generate reference intervals. The 14 dogs with abnormalities had more than trivial MR (12 dogs), subaortic stenosis (one dog), and equivocal subaortic stenosis (one dog). The 44 males were heavier than 59 females (P<0.001) and had a larger maximum left atrial dimension (P=0.015), left ventricular internal dimension at end-diastole (P<0.001) and systole (P<0.001), and thicker interventricular septum thickness at end-diastole (P=0.016). A positive linear correlation was identified between bodyweight and aortic root and left atrial diameters and left ventricular dimensions and between age and aortic root and left atrial diameter and peak late transmitral flow velocity. A negative linear correlation was identified between age and peak early transmitral flow velocity and the ratio between peak early and late transmitral flow velocities. No differences in echocardiographic-derived cardiac dimensions were detected between healthy dogs and dogs with more than trivial MR. In this population of CWDs, subclinical cardiac abnormalities were uncommon, and they were mainly classified as MR. [ABSTRACT FROM AUTHOR]

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

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

Chest radiography for mitral valve endocardiosis (MMVD) is both an independent and an additional method of investigation compared to echocardiography. It allows assessment of lung tissue condition, central airways, degree of vascularization, and changes in the mediastinum and pleural cavities. This study aimed to perform a radiographic examination of dogs with mitral valve endocardiosis at different stages under previously established and new indices and to determine their informativeness. The study was conducted in the private veterinary hospital “Eurovet” and at the Department of Internal Diseases of Animals and Clinical Diagnostics clinic of the Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies of Lviv. The subjects were 25 dogs with mitral valve endocardiosis. The diagnosis was established based on the American College of Veterinary Medicine criteria. During the study, three experimental groups of animals were formed according to their clinical-functional status and the characteristics of each stage of MMVD development: groups B1, B2, and C. In group B1, 57.1 % of the animals had a slight increase in the RLAD index. With the progression of the disease, we observed a further increase in RLAD (in 80 %), a significant increase in VLAS (P < 0.01) for the first time in 40 %, as well as a decrease in RLAD-spine (P < 0.05) in 40 % and Bronchus-spine (P < 0.01) in 60 % of dogs, which generally indicates both local enlargement of the left atrium and cardiomegaly. The informativeness of the VHS index was noted at stage C (group C), as in 66.7 % of the experimental animals, its value exceeded (P < 0.001) the reference values of the norm. At the same time, we observed an increase (P < 0.05) in the mean value of RLAD by 1.3 times compared to group B1 and VLAS (P < 0.001) by 1.6 times. Between the radiographic indicators, we confirmed the presence of a strong correlation. Thus, in group B2, it was positive (r = +0.779) for VHS and RLAD and negative (r = -0.831) for VHS and RLAD-spine. In group C, a further increase in the correlation (r = +0.885) was found only between VHS and RLAD. Based on the analysis of chest radiography data, it is advisable to use radiographic indices in cases of cardiomegaly, particularly with left atrial enlargement. However, this requires their group determination and mandatory comparison with echocardiographic examination results. In veterinary practice, this has diagnostic significance for establishing the stage of the disease, as well as in the selection or correction of the therapeutic support scheme for the patient. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Myxomatous mitral valve disease is dogs' most common acquired heart disease. The gold standard for its definitive diagnosis is echocardiography. This study aimed to develop a tool that uses a quality of life survey, structured anamnesis, and physical examination to predict the American College of Veterinary Internal Medicine classification stages. Accurately identifying a patient's stage is crucial to evaluating when treatment should be initiated and tailoring it to their ACVIM stage. The study analysed 1011 dogs from 23 hospitals, and the results showed that the majority of patients were successfully classified into the control group (healthy dogs), stage B (dogs with a heart murmur but are asymptomatic), and stage C (dogs with heart failure). However, efficient results were not obtained to differentiate between stage B1 (dogs with a heart murmur and without heart enlargement) and stage B2 (dogs with a heart murmur and heart enlargement). Further studies should be carried out to implement these techniques and improve their diagnostic value in veterinary cardiology. Myxomatous mitral valve disease (MMVD) is a prevalent canine cardiac disease typically diagnosed and classified using echocardiography. However, accessibility to this technique can be limited in first-opinion clinics. This study aimed to determine if machine learning techniques can classify MMVD according to the ACVIM classification (B1, B2, C, and D) through a structured anamnesis, quality of life survey, and physical examination. This report encompassed 23 veterinary hospitals and assessed 1011 dogs for MMVD using the FETCH-Q quality of life survey, clinical history, physical examination, and basic echocardiography. Employing a classification tree and a random forest analysis, the complex model accurately identified 96.9% of control group dogs, 49.8% of B1, 62.2% of B2, 77.2% of C, and 7.7% of D cases. To enhance clinical utility, a simplified model grouping B1 and B2 and C and D into categories B and CD improved accuracy rates to 90.8% for stage B, 73.4% for stages CD, and 93.8% for the control group. In conclusion, the current machine-learning technique was able to stage healthy dogs and dogs with MMVD classified into stages B and CD in the majority of dogs using quality of life surveys, medical history, and physical examinations. However, the technique faces difficulties differentiating between stages B1 and B2 and determining between advanced stages of the disease. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Myxomatous mitral valve disease (MMVD) stands as a prevalent cardiac ailment in the canine population, with the potential to culminate in heart failure. Within the pathogenesis of this condition, oxidative stress assumes a pivotal role, possibly impacting the functionality of the heart's primary energy production center, the mitochondria. We noticed a gap in research regarding changes in mitochondrial DNA in dogs with this condition. Our study aimed to fill this gap by examining mitochondrial DNA and oxidative stress at different stages of myxomatous mitral valve disease in dogs. Our findings showed that in the early stages of the disease, mitochondrial DNA levels were lower in affected dogs compared to healthy ones. However, mitochondrial DNA levels slightly increased as the disease progressed to the heart failure stage. Additionally, we observed that oxidative stress, a harmful process in the body, increased in dogs with heart disease. Dogs diagnosed with heart failure who received therapeutic interventions exhibited a modest abatement in oxidative stress levels. Our study suggests that in canine myxomatous mitral valve disease, alterations in mitochondrial DNA and elevated oxidative stress manifest in the advanced stages of the condition. These findings shed light on the intricate dynamics of this disease and prompt contemplation regarding the utility of mitochondrial DNA as a potential biomarker for the assessment and prognosis of heart conditions in dogs, thereby illuminating a prospective avenue for further research. Myxomatous mitral valve disease (MMVD) is the most common heart disease in small-breed dogs, often leading to heart failure. Oxidative stress in MMVD can harm mitochondria, decreasing their DNA content. This study assesses dogs' oxidative stress and mitochondrial DNA at different MMVD stages. Fifty-five small-breed dogs were categorized into four groups, including: A—healthy (n = 15); B—subclinical (n = 15); C—heart failure (n = 15); and D—end-stage MMVD (n = 10). Serum malondialdehyde (MDA) and mitochondrial DNA in peripheral blood were analyzed. Quantitative real-time PCR measured mitochondrial DNA, and PCR data were analyzed via the fold-change Ct method. Serum MDA levels were assessed using competitive high-performance liquid chromatography (HPLC). Mitochondrial DNA was significantly lower in group B (−0.89 ± 2.82) than in group A (1.50 ± 2.01), but significantly higher in groups C (2.02 ± 1.44) and D (2.77 ± 1.76) than B. MDA levels were notably elevated in groups B (19.07 ± 11.87 µg/mL), C (23.41 ± 12.87 μg/mL), and D (19.72 ± 16.81 μg/mL) in comparison to group A (9.37 ± 4.67 μg/mL). Nevertheless, this observed difference did not reach statistical significance. It is noteworthy that mitochondrial DNA content experiences a decline during the subclinical stage but undergoes an increase in cases of heart failure. Concurrently, oxidative stress exhibits an upward trend in dogs with MMVD. These findings collectively suggest a potential association between mitochondrial DNA, oxidative stress, and the progression of MMVD in small-breed dogs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the feasibility of isometric myography in pet dogs with myxomatous mitral valve disease (MMVD) to determine its use in quantifying endothelial dysfunction. ANIMALS: 9 dogs euthanized for medical reasons. METHODS: Femoral, renal, and mesenteric arteries were collected postmortem and stored in physiological saline solution at 4°C for myography. Mitral valves were scored for myxomatous degeneration (grades 1 to 4). Sections of arteries were mounted in wells, immersed in physiological saline solution perfused with 95% O2 and 5% CO2 at 37°C, and stretched to an internal circumference (IC) that generated the maximal difference between active and passive wall tension (IC1). Normalization factors were calculated by dividing the IC1 by the IC at which the passive wall tension was 100 mm Hg (IC100). Vasoconstriction to phenylephrine and vasodilation to acetylcholine (endothelial dependent) and sodium nitroprusside (endothelial independent) were assessed by cumulative dose-response curves. RESULTS: Median MMVD grade was 3. Mean values of normalization factors were 1.00 ± 0.14 (renal, n = 15), 1.00 ± 0.10 (femoral, 8), and 1.05 ± 0.12 (mesenteric, 6). Responses to phenylephrine were similar between dogs (P = .14). Reduced responses to acetylcholine compared with sodium nitroprusside were identified in 15 arteries, suggesting endothelial dysfunction. CLINICAL RELEVANCE: Isometric myography of arteries from pet dogs is feasible and can identify loss of endothelial-dependent relaxation in dogs with MMVD postmortem. Its use in further research can lead to a better understanding of the pathophysiology mechanisms of this disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the effects of cardiac cachexia on the metabolomic profile in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: 3 groups of dogs with MMVD enrolled between November 30, 2018, and April 7, 2022: (1) Dogs with congestive heart failure (CHF) and cachexia (CHF-cachexia group; n = 10); (2) dogs with CHF that had no cachexia (CHF-no cachexia group; n = 10); and (3) dogs with asymptomatic disease (American College of Veterinary Internal Medicine [ACVIM] Stage B2) with no cachexia (B2 group; n = 10). METHODS: Metabolomic profiles were analyzed from serum samples using ultra-high-performance liquid chromatographytandem mass spectroscopy. Dogs in the 3 groups were compared, with statistical significance defined as P < .05 with a low false discovery rate (q < .10) and nominal statistical significance defined as P < .05 but q > .10. RESULTS: Numerous metabolites were significantly (n = 201) or nominally significantly (n = 345) different between groups. For example, when comparing the CHF-cachexia vs CHF-no cachexia groups, lipids were the predominant metabolite differences, including many medium- and long-chain dicarboxylates and dicarboxylate acylcarnitines. For comparisons of the CHF-cachexia vs B2 groups and the CHF-no cachexia vs B2 groups, amino acids, nucleotides, and cofactors/vitamins were the predominant metabolite differences. CLINICAL RELEVANCE: Some significant metabolite differences were identified between dogs with and without cardiac cachexia. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium‐to‐aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. Hypothesis/Objectives A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. Animals One hundred twenty‐seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. Methods Randomized double‐blinded controlled multicenter clinical trial. Results The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end‐diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%‐13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%‐12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). Conclusions and Clinical Importance Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.

Simple Summary: The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are inflammatory indicators calculated using blood counts that serve as potential biomarkers in various diseases. This study investigated healthy dogs and those with a common heart disease, myxomatous mitral valve disease (MMVD). Dogs with MMVD had higher NLR, MLR, and PLR, which could be useful for diagnosing and predicting this condition. 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. [ABSTRACT FROM AUTHOR]

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

Simple Summary: The present study investigates the hypothesis that the thoracic inlet heart score (TIHS), a recently described method to assess the cardiac silhouette on dogs' chest radiographs, can be used to identify dogs with cardiac enlargement secondary to myxomatous mitral valve disease (MMVD). This method uses the thoracic inlet length as a reference point. Degenerative mitral valve disease is the most common acquired cardiac disease in dogs and radiographic studies are important in its diagnosis and follow up. The VHS and VLAS are recommended radiographic measurements to use in the staging of the disease. The TIHS method is simple to perform and provides practitioners with another tool when evaluating dogs with clinical signs compatible with cardiac disease. Comparing the results obtained from clinically healthy dogs and dogs in different MMVD Stage, we found that this method identified dogs with cardiac enlargement secondary to MMVD, and it could differentiate dogs in different MMVD stage. The diagnostic value of the vertebral heart size (VHS) in dogs with mitral valve degeneration (MVD) is compromised when middle thoracic vertebral anomalies are present. The objective of this study was to assess the use of the thoracic inlet heart score (TIHS) to identify left heart enlargement (LHE) secondary to MVD. The cardiac silhouette of 50 clinically healthy dogs and 106 MVD dogs in different stages was assessed on a right lateral chest radiograph. The TIHS and VHS value were calculated for each patient and compared. The TIHS was significantly different between the control dogs and the dogs with MMVD, increasing with disease stage, control 2.91 ± 0.23, Stage B1 2.98 ± 0.36, B2 3.25 ± 0.34, and C 3.53 ± 0.36, p < 0.05. A THIS ≥3.3 showed 69% sensitivity and 81% specificity to identify LHE. The TIHS showed moderate correlation with the VHS, LA/Ao, and LVIDDN 0.59, 0.42, and 0.62, respectively. The intraobserver and interobserver agreement were almost perfect, 0.96, and substantial, 0.73. The TIHS method can be used to identify LHE secondary to MMVD on dogs' thoracic radiographs. [ABSTRACT FROM AUTHOR]

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

Although deep learning has been explored extensively for computer-aided medical imaging diagnosis in human medicine, very little has been done in veterinary medicine. The goal of this retrospective, pilot project was to apply the deep learning artificial intelligence technique using thoracic radiographs for detection of canine left atrial enlargement and compare results with those of veterinary radiologist interpretations. Seven hundred ninety-two right lateral radiographs from canine patients with thoracic radiographs and contemporaneous echocardiograms were used to train, validate, and test a convolutional neural network algorithm. The accuracy, sensitivity, and specificity for determination of left atrial enlargement were then compared with those of board-certified veterinary radiologists as recorded on radiology reports. The accuracy, sensitivity, and specificity were 82.71%, 68.42%, and 87.09%, respectively, using an accuracy driven variant of the convolutional neural network algorithm and 79.01%, 73.68%, and 80.64%, respectively, using a sensitivity driven variant. By comparison, accuracy, sensitivity, and specificity achieved by board-certified veterinary radiologists was 82.71%, 68.42%, and 87.09%, respectively. Although overall accuracy of the accuracy driven convolutional neural network algorithm and veterinary radiologists was identical, concordance between the two approaches was 85.19%. This study documents proof-of-concept for application of deep learning techniques for computer-aided diagnosis in veterinary medicine.

Abstract Background 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. Objective This study aims to investigate the prognostic value of Cys‐C in dogs with MMVD. Animals Fifty client‐owned small‐breed dogs with MMVD were included in this study. Methods 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. Results Serum Cys‐C concentrations were significantly associated with MMVD‐related death (P

Abstract Background Information regarding the frequency of L waves and their prognostic relevance in dogs with secondary atrial fibrillation (AF) is limited. Hypothesis/Objectives To determine whether L waves occur and ascertain their prognostic role, as well as the role of other clinical and echocardiographic variables in dogs with AF. Animals Fifty‐five dogs with AF associated with myxomatous mitral valve disease or dilated cardiomyopathy. Methods Retrospective, multicenter observational study. In addition to L waves analysis, other clinical and echocardiographic variables, including type of antiarrhythmic treatment, were evaluated. A survival analysis was performed to test for predictors of cardiac death and all‐cause mortality using Cox proportional hazards regression models. Results L waves were evident in 33/55 dogs (60%, 95% confidence interval [CI] = 47%‐72%) but their presence did not influence outcome. Increased left ventricular end‐systolic diameter normalized for body weight (LVSDn) was a significant predictor of both cardiac death (hazard ratio [HR] = 4.41, 95% CI = 1.18‐16.54; P = .03) and all‐cause mortality (HR = 9.39, 95% CI = 2.49‐35.32; P

Abstract Background Myxomatous mitral valve disease (MMVD) is the most common diagnosed cardiovascular disease in dogs. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) tests are used to diagnose congestive heart failure, but there are conflicting reports about their value in diagnosing the subclinical stages of MMVD in dogs. Moreover, the diagnostic value of blood lipoproteins in dogs with MMVD is still unclear. The purpose of this study was to assess the serum concentrations of ANP, BNP and lipoproteins of dogs with MMVD and to evaluate the correlation of the levels of ANP and BNP with lipoproteins. Results This study was performed on 24 dogs with MMVD and 10 healthy dogs. Dogs with MMVD were classified in to stages B1 (n = 11), B2 (n = 6), C (n = 4) and D (n = 3) groups according to the classification suggested by American College of Veterinary Internal Medicine guidelines. Our results showed that the mean serum BNP levels were significantly increased for all MMVD groups compared to control dogs. The mean serum ANP levels for the stage B2, C and D groups were significantly higher than the control group, while the mean serum ANP concentrations did not differ significantly between the stage B1 and control groups. An increase in BNP level was observed in 87.5% of patients. Although BNP concentrations were elevated in 100% of dogs with stages C, D and B2, high BNP was observed in 72.72% of dogs with stage B1. Regarding ANP, 58.33% of patients had an increase in ANP. However, elevated ANP levels were found in only 27.27% of patients in stage B1, while increased ANP levels were observed in 66.66 and 100% of patients in stage B2 and C/D groups respectively. Also, in all patients with MMVD, the mean serum concentrations of high-density lipoprotein cholesterol (HDL-C) were approximately 1.7 to 2 times significantly lower than the control group. Additionally, the mean serum low-density lipoprotein cholesterol (LDL-C) increased significantly (1.9-2.7 times) compared to the control group. There was a significant inverse correlation between HDL-C and BNP, and HDL-C and ANP. LDL-C showed a significant positive correlation with BNP, and ANP. Also, LDL-C, but not HDL-C, had a significant positive correlation with LA/AO ratio, LVIDd, LVIDdN and VHS. BNP and ANP showed a significant positive correlation with LA/AO, LVIDd, LVIDdN and VHS. Conclusions Serum BNP has a greater diagnostic value than serum ANP in dogs with MMVD. In addition, serum BNP can be used to determine the subclinical stages of B1 and B2 MMVD. This study also suggests that dogs with subclinical MMVD, showed an increase in BNP along with a decrease in HDL-C and an increase in LDL-C, which are known to be risk factors for cardiovascular diseases in human. However, it seems that high LDL-C is more involved in the pathogenesis of MMVD than low HDL-C. Therefore, periodic testing of serum lipoproteins is recommended in high-risk patients, even if total cholesterol levels are normal.

Abstract Background The EPIC study defines criteria, including echocardiographic assessments of left atrial to aortic ratio (LA: Ao) and left ventricular internal diameter in diastole normalized for body weight (LVIDdN), for dogs with preclinical myxomatous mitral valve disease (MMVD) likely to benefit from pimobendan therapy. Access to echocardiography by a cardiologist is not universally available. Hypothesis/Objectives Completion of a focused echocardiographic training program would result in accurate identification of dogs fulfilling the EPIC criteria by primary care veterinarians (PC). Participants Six PCs with no previous echocardiographic experience. Methods Prospective diagnostic test accuracy study. After training, each PC evaluated ≤10 dogs that they believed to have preclinical MMVD. The evaluation was repeated by 1 of 3 cardiology diplomates, blinded to the PC's findings. Agreement between clinical assessments and echocardiographic measurements was assessed. Results Fifty‐seven dogs were evaluated by PCs; 1 dog was withdrawn because of congestive heart failure. The median time between PC and cardiologist evaluation was 0 days (range, 0‐8). One incorrect diagnosis of MMVD was made by a PC (this dog had dilated cardiomyopathy [DCM]); preclinical MMVD was confirmed by the cardiologist in 55 dogs. No difference in LA: Ao (P = .96; CV = 6.9%) was detected between PCs and cardiologists. LVIDdN (1.69 cm/kg0.294 (1.26‐2.21) vs 1.73 cm/kg0.294 (1.32‐2.73); P = .001; CV = 6.5%), was significantly lower when measured by PCs vs cardiologists. PCs and cardiologists agreed regarding assessment of EPIC criteria in 49/56 dogs (Alpha = .761, 95% confidence interval 0.697‐0.922). Conclusions and Clinical Importance The program effectively trained PCs to accurately assess EPIC criteria in dogs with preclinical MMVD.

BackgroundTGFβ signaling appears to contribute to the pathogenesis of myxomatous mitral valve disease (MMVD) in both dogs and humans. However, little is known about the extent of the downstream signaling changes that will then affect cell phenotype and function in both species.ObjectiveIdentify changes in downstream signals in the TGFβ pathway in canine MMVD and examine the effects of antagonism of one significant signal (SMAD2 was selected).Materials and methodsCanine cultures of normal quiescent valve interstitial cells (qVICs) and disease-derived activated myofibroblasts (aVICs) (n = 6) were examined for TGFβ signaling protein expression using a commercial antibody array. Significant changes were confirmed, and additional proteins of interest downstream in the TGFβ signaling pathway and markers of cell phenotype were examined (PRAS40, S6K, elF4E IRS-1, αSMA, and VIM), using protein immunoblotting. RT-PCR examined expression of gene markers of VIC activation (ACTA2, TAGLN, and MYH10; encoding the proteins αSMA, SM22, and Smemb, respectively). Attenuation of pSMAD2 in aVICs was examined using a combination of RNA interference technology (siRNA) and the SMAD7 (antagonizes SMAD2) agonist asiaticoside.ResultsThe antibody array identified significant changes (P < 0.05) in 19 proteins, of which six were phosphorylated (p). There was increased expression of pSMAD2 and pRAC1 and decreased expression of pmTOR, pERK1/2, and pAKT1. Expression of pPRAS40 and pIRS-1 was increased, as was the mTOR downstream transcription factor pS6K, with increased expression of peIF4E in aVICs, indicating negative feedback control of the PI3K/AKT/mTOR pathway. SMAD2 antagonism by siRNA and the SMAD7 agonist asiaticoside decreased detection of pSMAD by at least 50%, significantly decreased expression of the aVIC gene markers ACTA2, TAGLN, and MYH10, and pαSMA, pAKT2, and pERK1, but had no effect on pS6K, pERK2, or pVIM expression in aVICs. SMAD2 antagonism transitioned diseased aVICs to normal qVICs, while maintaining a mesenchymal phenotype (VIM+) while concurrently affecting non-canonical TGFβ signaling.ConclusionMMVD is associated with changes in both the canonical and non-canonical TGFβ signaling pathway. Antagonism of SMAD2 transitions diseased-activated myofibroblasts back to a normal phenotype, providing data that will inform studies on developing novel therapeutics to treat MMVD in dogs and humans.

Background: Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium‐to‐aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. Hypothesis/Objectives: A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. Animals: One hundred twenty‐seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. Methods: Randomized double‐blinded controlled multicenter clinical trial. Results: The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end‐diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%‐13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%‐12.5%) in dogs receiving control diet (P =.79). Neither component of the primary outcome measure was significantly different between groups (LAD, P =.65; LVIDd, P =.92). No difference was found in mitral valve E wave velocity (P =.36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P =.41). Conclusions and Clinical Importance: Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control. [ABSTRACT FROM AUTHOR]

BackgroundPulmonary hypertension (PH) is a common complication of cardiopulmonary disease. In dogs, PH commonly occurs secondary to myxomatous mitral valve disease (MMVD). Red blood cell and platelet indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), mean platelet volume (MPV) and platelet distribution width (PDW), have previously been found to be indicators for predicting and prognosing PH in humans. Therefore, this study aimed to investigate whether these indices are associated with MMVD and/or PH in dogs.MethodsTwo hundred and forty-six dogs were retrospectively recruited for the study and classified into 4 groups: normal (n = 49), MMVD (n =102), PH (n =17), MMVD+PH (n =78). A sub-analysis was performed in dogs with MMVD without evidence of PH according to stage B1 (n =20), stage B2 (n =15), stage C (n =67). The data are expressed as median (interquartile range).Results and discussionNo significant differences (p

An algorithm based on artificial intelligence (AI) was developed and tested to classify different stages of myxomatous mitral valve disease (MMVD) from canine thoracic radiographs. The radiographs were selected from the medical databases of two different institutions, considering dogs over 6 years of age that had undergone chest X-ray and echocardiographic examination. Only radiographs clearly showing the cardiac silhouette were considered. The convolutional neural network (CNN) was trained on both the right and left lateral and/or ventro-dorsal or dorso-ventral views. Each dog was classified according to the American College of Veterinary Internal Medicine (ACVIM) guidelines as stage B1, B2 or C + D. ResNet18 CNN was used as a classification network, and the results were evaluated using confusion matrices, receiver operating characteristic curves, and t-SNE and UMAP projections. The area under the curve (AUC) showed good heart-CNN performance in determining the MMVD stage from the lateral views with an AUC of 0.87, 0.77, and 0.88 for stages B1, B2, and C + D, respectively. The high accuracy of the algorithm in predicting the MMVD stage suggests that it could stand as a useful support tool in the interpretation of canine thoracic radiographs.

IntroductionCardiovascular and renal diseases are known to affect each other in the cardiovascular renal axis disorder (CvRD). Although CvRD, which includes myxomatous mitral valve disease (MMVD) and chronic kidney disease (CKD), has been described in dogs, there are only a few reports on the progression of CKD in accordance with the severity of MMVD. The aim of this study was to evaluate whether the presence of MMVD is associated with the rate of progression of CKD in dogs. The time from the initial diagnosis to the worsening of the International Renal Interest Society (IRIS) stage and the time for the occurrence of hyperphosphatemia and isosthenuria were evaluated.Materials and methodsIn this retrospective study, CKD progression was determined as an increase in the IRIS stage by at least one level and the development of hyperphosphatemia or isosthenuria. The CKD progression was compared in dogs with and without comorbid MMVD.ResultsDogs with CKD were divided into two groups: dogs with and without MMVD (n = 63, concurrent group; n = 52, CKD group, respectively). The concurrent group was further divided into two subgroups based on the American College of Veterinary Internal Medicine guidelines (B1 group, n = 24; B2 group, n = 39). The time for progression of CKD from IRIS stage 1 to IRIS stage 2 was significantly shorter in the concurrent group than in the CKD group (log-rank test, p < 0.001). MMVD was associated with an increased risk of progression from stage 1 to stage 2 (hazard ratio, 6.442; 95% confidence interval (CI), 2.354 to 18.850; p < 0.001). The timing of the onset of hyperphosphatemia or isosthenuria in the concurrent group and the CKD group was not significantly different.ConclusionThe results of this study suggest that MMVD could be a risk factor for the progression of CKD. Our findings may help predict the prognosis of dogs with both CKD and MMVD compared to CKD only.

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.

Myxomatous mitral valve disease (MMVD) is a prevalent canine cardiac disease typically diagnosed and classified using echocardiography. However, accessibility to this technique can be limited in first-opinion clinics. This study aimed to determine if machine learning techniques can classify MMVD according to the ACVIM classification (B1, B2, C, and D) through a structured anamnesis, quality of life survey, and physical examination. This report encompassed 23 veterinary hospitals and assessed 1011 dogs for MMVD using the FETCH-Q quality of life survey, clinical history, physical examination, and basic echocardiography. Employing a classification tree and a random forest analysis, the complex model accurately identified 96.9% of control group dogs, 49.8% of B1, 62.2% of B2, 77.2% of C, and 7.7% of D cases. To enhance clinical utility, a simplified model grouping B1 and B2 and C and D into categories B and CD improved accuracy rates to 90.8% for stage B, 73.4% for stages CD, and 93.8% for the control group. In conclusion, the current machine-learning technique was able to stage healthy dogs and dogs with MMVD classified into stages B and CD in the majority of dogs using quality of life surveys, medical history, and physical examinations. However, the technique faces difficulties differentiating between stages B1 and B2 and determining between advanced stages of the disease.

Canine myxomatous mitral valve disease (MMVD) is similar to Barlow's form of MMVD in humans. These valvulopathies are complex, with varying speeds of progression. We hypothesized that the relative abundances of serum proteins would help identify the consecutive MMVD stages and discover new disease pathways on a systemic level. To identify distinction-contributing protein panels for disease onset and progression, we compared the proteomic profiles of serum from healthy dogs and dogs with different stages of naturally occurring MMVD. Dogs were divided into experimental groups on the basis of the left-atrium-to-aorta ratio and normalized left ventricular internal dimension in diastole values. Serum was collected from healthy (N = 12) dogs, dogs diagnosed with MMVD in stages B1 (N = 13) and B2 (N = 12) (asymptomatic), and dogs diagnosed with MMVD in chronic stage C (N = 13) (symptomatic). Serum biochemistry and selected ELISAs (galectin-3, suppression of tumorigenicity, and asymmetric dimethylarginine) were performed. Liquid chromatography–mass spectrometry (LC–MS), tandem mass tag (TMT) quantitative proteomics, and statistical and bioinformatics analysis were employed. Most of the 21 serum proteins with significantly different abundances between experimental groups (p < 0.05, FDR ˂ 0.05) were classified as matrix metalloproteinases, protease inhibitors, scaffold/adaptor proteins, complement components, anticoagulants, cytokine, and chaperone. LC–MS TMT proteomics results obtained for haptoglobin, clusterin, and peptidase D were further validated analytically. Canine MMVD stages, including, for the first time, asymptomatic B1 and B2 stages, were successfully distinguished in dogs with the disease and healthy dogs on the basis of the relative abundances of a panel of specific serum proteins. Most proteins with significantly different abundances were involved in immune and inflammatory pathways. Their role in structural remodeling and progression of canine MMVD must be further investigated. Further research is needed to confirm the resemblance/difference with human MMVD. Proteomics data are available via ProteomeXchange with the unique dataset identifier PXD038475. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: This study aims to investigate the prognostic value of Cys‐C in dogs with MMVD. Animals: Fifty client‐owned small‐breed dogs with MMVD were included in this study. Methods: 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. Results: 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). Conclusions and Clinical Importance: 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 creatinine concentration. [ABSTRACT FROM AUTHOR]

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

Impaired mitochondria cause an impressive decrease in ATP production becoming a common condition of cardiovascular diseases. Myxomatous mitral valve disease (MMVD) is characterized by mitochondrial dysfunction. By a non-invasive procedure of metabolism analysis on peripheral blood mononuclear cells, we exploit ex-vivo studies that directly constitute a translational approach to evaluate the cell bioenergetics. Cell ATP production decreased in the presence of MMVD, whereas glycolysis was unaffected. In MMVD, the mitochondrial activity underwent a significant reduction of basal respiration, maximal respiration, and ATP production. Our results depicted a pathological condition of MMVD characterized by cell metabolism deprived of mitochondrial energy support. • PBMCs are used to evaluate mitochondrial function in myxomatous mitral valve disease (MMVD). • Glycolysis is unaffected in the presence of MMVD. • The cell metabolism in MMVD is deprived of mitochondrial bioenergetics. [ABSTRACT FROM AUTHOR]

Background: Information regarding the frequency of L waves and their prognostic relevance in dogs with secondary atrial fibrillation (AF) is limited. Hypothesis/Objectives: To determine whether L waves occur and ascertain their prognostic role, as well as the role of other clinical and echocardiographic variables in dogs with AF. Animals: Fifty‐five dogs with AF associated with myxomatous mitral valve disease or dilated cardiomyopathy. Methods: Retrospective, multicenter observational study. In addition to L waves analysis, other clinical and echocardiographic variables, including type of antiarrhythmic treatment, were evaluated. A survival analysis was performed to test for predictors of cardiac death and all‐cause mortality using Cox proportional hazards regression models. Results: L waves were evident in 33/55 dogs (60%, 95% confidence interval [CI] = 47%‐72%) but their presence did not influence outcome. Increased left ventricular end‐systolic diameter normalized for body weight (LVSDn) was a significant predictor of both cardiac death (hazard ratio [HR] = 4.41, 95% CI = 1.18‐16.54; P =.03) and all‐cause mortality (HR = 9.39, 95% CI = 2.49‐35.32; P <.001). Heart rate assessed during echocardiography (Echo‐HR) represented an additional significant predictor of cardiac death (HR = 1.01, 95% CI = 1.00‐1.01; P =.04) and all‐cause mortality (HR = 1.01, 95% CI = 1.00‐1.01; P =.04). Conclusions and Clinical Importance: L waves occurred frequently in dogs with AF, but held no prognostic relevance. Conversely, LVSDn and Echo‐HR represented independent predictors of negative outcome in these animals. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is an important predictor of poor outcomes in dogs with mitral regurgitation (MR). The feasibility of radiography to predict PH in dogs with MR is unknown. This retrospective, observational, and analytic study aimed to identify a radiographic parameter to predict PH in dogs with MR. A total of 302 dogs diagnosed with MR on echocardiography were enrolled. Medical record and radiographic findings such as the size of the main pulmonary artery, left atrium, left ventricle, and right chamber, and cranial and caudal pulmonary arteries and veins were evaluated according to the presence of PH. The diameters of the cranial and caudal pulmonary vessels were compared to the fourth rib and the ninth rib, respectively, and the ratio of the pulmonary artery to the corresponding vein (CdPA/CdPV) was calculated. Pulmonary hypertension was diagnosed in 77 dogs (25.5%) and the prevalence of PH increased with MR grade. The CdPA/CdPV was significantly higher (P < 0.001) in the presence of PH. Multivariate analysis showed that the CdPA/CdPV was the only independent radiographic parameter that had a significant association with PH in dogs with MR (P = 0.028). The cut‐off value of the CdPA/CdPV = 1.10 showed 90.6% specificity and 31.1% sensitivity for detecting PH in dogs with MR. In dogs with MR, PH can be predicted with high specificity when the caudal pulmonary artery is 1.1 times larger than the corresponding vein on radiographs. [ABSTRACT FROM AUTHOR]

Background: Myxomatous mitral valve disease (MMVD) is the most common diagnosed cardiovascular disease in dogs. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) tests are used to diagnose congestive heart failure, but there are conflicting reports about their value in diagnosing the subclinical stages of MMVD in dogs. Moreover, the diagnostic value of blood lipoproteins in dogs with MMVD is still unclear. The purpose of this study was to assess the serum concentrations of ANP, BNP and lipoproteins of dogs with MMVD and to evaluate the correlation of the levels of ANP and BNP with lipoproteins. Results: This study was performed on 24 dogs with MMVD and 10 healthy dogs. Dogs with MMVD were classified in to stages B1 (n = 11), B2 (n = 6), C (n = 4) and D (n = 3) groups according to the classification suggested by American College of Veterinary Internal Medicine guidelines. Our results showed that the mean serum BNP levels were significantly increased for all MMVD groups compared to control dogs. The mean serum ANP levels for the stage B2, C and D groups were significantly higher than the control group, while the mean serum ANP concentrations did not differ significantly between the stage B1 and control groups. An increase in BNP level was observed in 87.5% of patients. Although BNP concentrations were elevated in 100% of dogs with stages C, D and B2, high BNP was observed in 72.72% of dogs with stage B1. Regarding ANP, 58.33% of patients had an increase in ANP. However, elevated ANP levels were found in only 27.27% of patients in stage B1, while increased ANP levels were observed in 66.66 and 100% of patients in stage B2 and C/D groups respectively. Also, in all patients with MMVD, the mean serum concentrations of high-density lipoprotein cholesterol (HDL-C) were approximately 1.7 to 2 times significantly lower than the control group. Additionally, the mean serum low-density lipoprotein cholesterol (LDL-C) increased significantly (1.9-2.7 times) compared to the control group. There was a significant inverse correlation between HDL-C and BNP, and HDL-C and ANP. LDL-C showed a significant positive correlation with BNP, and ANP. Also, LDL-C, but not HDL-C, had a significant positive correlation with LA/AO ratio, LVIDd, LVIDdN and VHS. BNP and ANP showed a significant positive correlation with LA/AO, LVIDd, LVIDdN and VHS. Conclusions: Serum BNP has a greater diagnostic value than serum ANP in dogs with MMVD. In addition, serum BNP can be used to determine the subclinical stages of B1 and B2 MMVD. This study also suggests that dogs with subclinical MMVD, showed an increase in BNP along with a decrease in HDL-C and an increase in LDL-C, which are known to be risk factors for cardiovascular diseases in human. However, it seems that high LDL-C is more involved in the pathogenesis of MMVD than low HDL-C. Therefore, periodic testing of serum lipoproteins is recommended in high-risk patients, even if total cholesterol levels are normal. [ABSTRACT FROM AUTHOR]

The most common cardiovascular disease in domestic dogs is myxomatous mitral valve disease (MMVD), accounting for 75% of all cardiac disease. An increase in age is generally associated with increased incidence of the disease, but Cavalier King Charles Spaniels (CKCS) exhibit an unusually high prevalence of early-onset MMVD, and thus, potentially greater cardiac morbidity and mortality compared to other breeds. Previous research has suggested that selected candidate risk alleles for MMVD are fixed in CKCSs, including six locations within the Nebulette (NEBL) gene on CFA2. The current study analysed genotypes of 180 Australian CKCSs at the identified risk loci. Of these, 178 were phenotyped for severity of disease by echocardiographic measurements of left atrium to aortic root ratio (LA:Ao) and weight normalised left ventricular end diastolic diameter (LVIDdN). Genotyping array markers correctly predicted the genotype at the risk-variant loci in the CKCS population, and the NEBL1, NEBL2 and NEBL3 variants were observed to be in perfect linkage disequilibrium in this cohort. The CKCS cohort included 6/178 dogs being heterozygous for the protective/wild-type alleles at the NEBL locus. The mean LA:Ao and LVIDdN scores of these dogs heterozygous at NEBL1-3 variants were significantly smaller, and with significantly lower variance compared to age-matched CKCSs that were homozygous for risk alleles. The lower cardiac measurements in the heterozygous dogs indicate a significantly reduced risk of severe MMVD disease. Our analysis suggests that despite relative fixation of the NEBL risk alleles, healthy reference alleles at NEBL1-3 exist in low frequency in the CKCS breed and can be used to reduce MMVD severity and mortality. [ABSTRACT FROM AUTHOR]

Background: The EPIC study defines criteria, including echocardiographic assessments of left atrial to aortic ratio (LA: Ao) and left ventricular internal diameter in diastole normalized for body weight (LVIDdN), for dogs with preclinical myxomatous mitral valve disease (MMVD) likely to benefit from pimobendan therapy. Access to echocardiography by a cardiologist is not universally available. Hypothesis/Objectives: Completion of a focused echocardiographic training program would result in accurate identification of dogs fulfilling the EPIC criteria by primary care veterinarians (PC). Participants: Six PCs with no previous echocardiographic experience. Methods: Prospective diagnostic test accuracy study. After training, each PC evaluated ≤10 dogs that they believed to have preclinical MMVD. The evaluation was repeated by 1 of 3 cardiology diplomates, blinded to the PC's findings. Agreement between clinical assessments and echocardiographic measurements was assessed. Results: Fifty‐seven dogs were evaluated by PCs; 1 dog was withdrawn because of congestive heart failure. The median time between PC and cardiologist evaluation was 0 days (range, 0‐8). One incorrect diagnosis of MMVD was made by a PC (this dog had dilated cardiomyopathy [DCM]); preclinical MMVD was confirmed by the cardiologist in 55 dogs. No difference in LA: Ao (P =.96; CV = 6.9%) was detected between PCs and cardiologists. LVIDdN (1.69 cm/kg0.294 (1.26‐2.21) vs 1.73 cm/kg0.294 (1.32‐2.73); P =.001; CV = 6.5%), was significantly lower when measured by PCs vs cardiologists. PCs and cardiologists agreed regarding assessment of EPIC criteria in 49/56 dogs (Alpha =.761, 95% confidence interval 0.697‐0.922). Conclusions and Clinical Importance: The program effectively trained PCs to accurately assess EPIC criteria in dogs with preclinical MMVD. [ABSTRACT FROM AUTHOR]