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Standard transthoracic echocardiography is considered the non-invasive gold standard for the diagnosis of most cardiac diseases. Defining reproducibility, repeatability, and reliability of this exam is imperative to reduce errors in clinical evaluations. The present study aimed at: 1) evaluating the reproducibility and repeatability of 15 echocardiographic parameters in dogs by analyzing measurements obtained from several operators with different levels of experience and comparing them to the ones obtained from two board-certified operators (gold standards - GSs); 2) assessing whether different formative paths have an influence on the variability of the echocardiographic measurements. Fifty-one operators have been included in this study, along with two diplomates of the European College of Veterinary Internal Medicine - Cardiology. Ten dogs were enrolled, 5 Golden Retrievers and 5 Cavalier King Charles Spaniels. Echocardiographic examination was performed on each dog by one GS and several operators on the same day. Results show that M-mode measurements of the interventricular septum and the left ventricular free wall are the least reliable ones since they show a high deviation from the GS and a poor inter-operator reproducibility. Differently, M-mode-obtained internal diameters of the left ventricle in systole and diastole, and measurements of the aortic annulus and root are the most reliable echocardiographic parameters, demonstrating that all the operators can correctly assess left ventricular systolic function and dilation, and evaluate the aortic valve. Furthermore, a specialist clinical activity, more than the acquired theoretical knowledge, affects the reliability of the echocardiographic examination by reducing the difference from the GS’ measurements.

Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD), with radiographs frequently used to screen for evidence of left-sided cardiomegaly secondary to MMVD. Vertebral heart size (VHS), vertebral left atrial size (VLAS), modified VLAS (M-VLAS), and radiographic left atrial dimension (RLAD) are reported as objective measurements of global heart size and left atrial size. Normal VHS in CKCS (10.6 ± 0.5) is reportedly higher than the non-breed-specific value (9.7±0.5). Breed-specific VLAS, M-VLAS, and RLAD cut-offs have not been reported in CKCS. The aim of this prospective reference interval study was to describe the VHS, VLAS, M-VLAS, and RLAD values for 30 clinically healthy adult CKCS. Inclusion criteria were unremarkable physical examination, normal echocardiography, and thoracic radiographs without malposition/abnormalities. There were 22 female and eight male dogs. Ages ranged from 1 to 6 years. The VHS mean value in our sample was 10.08 ± 0.56 (95% range, 9.87-10.29). This was significantly greater than a previously published general canine reference value of 9.7 ± 0.5 and significantly less than a previously published CKCS breed-specific value of 10.6 ± 0.5 (P < 0.01). Mean VLAS, M-VLAS, and the RLAD values in our study were 1.79 ± 0.3 (95% range, 1.68-1.9), 2.23 ± 0.44 (95% range, 2.06-2.39), and 1.2 ± 0.34 (95% range, 1.07-1.33), respectively. These were significantly less than previously published reference interval values (P < 0.001). The VHS, M-VLAS, and the RLAD were not affected by sex, body weight, or BCS; whereas the VLAS was moderately affected by body weight. Findings from this study can be used as background for future thoracic radiographic assessments in CKCS.

Echocardiographic evaluation is a diagnostic tool for the in vivo diagnosis of heart diseases. Specific and unique anatomical characteristics of the ophidian heart such as the single ventricular cavity, a tubular sinus venosus opening into the right atrium, the presence of three arterial trunks and extreme mobility in the coelomic cavity during the cardiac cycle directly affect echocardiographic examination. Twenty‐one awake, healthy ball pythons (Python regius) were analysed based on guidelines for performing echocardiographic examinations. Imaging in the sagittal plane demonstrated the caudal vena cava, sinus venosus valve (SVV) and right atrium and the various portions of the ventricle, horizontal septum, left aortic arch and pulmonary artery. Transverse imaging depicted the spatial relationship of the left and right aortic arches, the pulmonary artery and the horizontal septum. Basic knowledge of cardiac blood flow in reptiles is necessary to understand the echocardiographic anatomy. The flow of the arterial trunks and SVV was analysed using pulsed‐wave Doppler based on the approach used for humans and companion mammals. The walls and diameters of the cavum arteriosum, cavum venosum and cavum pulmonale were also evaluated. This study should improve the veterinarian's knowledge of ophidian heart basal physiology and contribute to the development of cardiology in reptiles., Echocardiography improves the opportunity to diagnose before necropsy, thanks to the evaluation of intracardiac flows. Physiological range allow the clinician an ante‐mortem diagnosis and an appropriate treatment for the individual subject.

The objectives of this retrospective, observer agreement study were to (a) test variability of radiographic left atrial dimension (RLAD) and vertebral left atrial size (VLAS) measurements among observers with different levels of expertise in thoracic radiology and cardiology, (b) assess whether one method is better than the other in detecting left atrial enlargement (LAE), and (c) assess the agreement among RLAD, VLAS, and American College of Veterinary Internal Medicine (ACVIM) classes. Seventy-four dogs (eight healthy and 66 with mitral valve disease) with thoracic radiographs and echocardiography performed on the same day were reviewed. Thirty showed echocardiographic LAE. Left atrial dimension was quantified using RLAD and VLAS by six different operators with three levels of clinical experience in veterinary cardiology/radiology. Vertebral heart score and fourth thoracic vertebra (T4) were also measured. Differences in T4, vertebral heart score (VHS), RLAD, and VLAS measurements were found among six operators and among the three levels of clinical expertise as well as between veterinary cardiology readers and veterinary radiology readers (P < .05). The area under the receiver operating characteristic (AUC) curve for VHS showed good performances for all observers and level and type of expertise; the AUC for RLAD and VLAS was suboptimal only for the radiology student. Our RLAD and VLAS cutoffs (1.9 and 2.43 v, respectively) were better related to qualitative radiographic than quantitative echocardiographic LAE evaluation. Radiographic LA dimension and VLAS showed an increase proportional to the worsening of the ACVIM class. In conclusion, these results allow us to affirm that RLAD and VLAS are reproducible measurements for detecting LAE. Better performances are associated with clinical expertise and background.

The aim of this work was to retrospectively evaluate the influence of pimobendan on the survival time (ST) of dogs with myxomatous mitral valve disease at different stages using an Inverse Probability Weighting (IPW) analysis. An IPW method was used to minimize confounding and IPW weighted time-repeated logistic model was used to approximate survival curves (SCs) and calculate survival differences. Subjects were allocated into exposed (E) and unexposed (U). Dogs in the American College of Veterinary Internal Medicine (ACVIM) B2 class treated with pimobendan (± ACE-inhibitors) were selected for the E group, as well as symptomatic patients (ACVIM class C) treated with triple (furosemide, ACE-inhibitor, pimobendan) or quadruple (furosemide, ACE-inhibitor, pimobendan and spironolactone) therapy. The U group included ACVIM class B2 dogs not treated with any medication and ACVIM C dogs treated with a combination of furosemide and ACE-inhibitor/spironolactone without pimobendan. The survival curve (SC) of the E group crossed the U group at 1634 days. The difference between the two SCs at the time of maximum survival difference in favor of the U group was 11.3% (CI 1.7%-20.9%) (significant), in favor of the E group was 3.9% (CI -8.6%-16.4%) (not significant) and at the mean ST was 3.6% (CI -8.5%-15.7%) (not significant) in favor of the E group. For times greater than 1634 days the survival was in favor of the E group, but there were no statistically significant differences in survival in favor of the E group in this clinical population.

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

The development and progression of myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) are difficult to predict. Thus, the identification of dogs with a morphotype associated with more severe mitral disease at a young age is desirable. The aims of this study were to: (1) describe the physical, morphometric, and echocardiographic features of class B1 MMVD-affected Cavalier King Charles Spaniels (CKCS) according to the American College of Veterinary Internal Medicine (ACVIM) guidelines; (2) evaluate the influence of morphometric physical measurements on murmur intensity, mitral valve prolapse (MVP), regurgitant jet size, and indexed mitral valve and annulus measurements. Fifty-two MMVD-affected CKCS were included in the ACVIM class B1. This is a prospective clinical cross-sectional study. Morphometric measurements, which included the body, thorax, and head sizes of each dog, were investigated to establish the association with heart murmur intensity, valvular and annular echocardiographic measurements, MVP, and regurgitant jet size, using inverse probability weighting (IPW) analyses to adjust for confounding. The IPW analyses showed that when the head length and nose length decreased, dogs had a more severe regurgitant jet size. Furthermore, subjects with a more pronounced head stop angle had thicker anterior mitral valve leaflets. A brachycephalic morphotype, as seen in dogs similar to the King Charles Spaniel breed in terms of cephalic morphology, is associated with a more severe regurgitant jet size and with valvular characteristics that are related to the most severe forms of MMVD.

The aim of this work was to retrospectively evaluate the influence of different therapeutic protocols (loop diuretics, ACE-inhibitors, spironolactone +/- pimobendan) on the survival time (ST) of dogs with myxomatous mitral valve disease at different stages using an Inverse Probability Weighting (IPW) analysis. An IPW method was used to minimize confounding and IPW weighted time-repeated logistic model was used to approximate survival curves (SCs) and calculate survival differences. Subjects were allocated into cases (CA) and controls (CO). Dogs in American College of Veterinary Internal Medicine (ACVIM) B2 class treated with pimobendan (+/- ACE-inhibitors) were selected for the CA group, as well as symptomatic patients (ACVIM class C) threated with triple (furosemide, ACE-inhibitor, pimobendan) or quadruple (furosemide, ACE-inhibitor, pimobendan and spironolactone) therapy. The CO group included ACVIM class B2 dogs not treated with any medication and ACVIM C dogs treated with a combination of furosemide and ACE-inhibitor/spironolactone without pimobendan.The SC of the CA group crossed the CO group at 1634 days. The difference between the two SCs at the time of maximum survival difference in favour of the CO group was 11.3% (CI 1.7%–20.9%) (significant), in favour of the CA group was 3.9% (CI -8.6%–16.4%) (not significant) and at the mean ST was 3.6% (CI -8.5%–15.7%) (not significant) in favour of the CA group. For times greater than 1634 days the survival was in favour of the CA group, there were no statistically significant differences in survival in favour of the CA group in this clinical population.

Development and progression of myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) are difficult to predict. Identification at a young age of dogs with a morphotype associated with more severe mitral disease is desirable. The aims of this study were to: 1) describe the physical, morphometric, and echocardiographic features of MMVD affected Cavalier King Charles Spaniels (CKCS) in American College of Veterinary Internal Medicine (ACVIM) class B1; 2) evaluate the influence of morphometric physical measurements on murmur intensity, mitral valve prolapse (MVP), regurgitant jet size and indexed mitral valve and annulus measurements. Fifty-two MMVD affected CKCS in ACVIM class B1 were included. This is a prospective clinical cross-sectional study. Morphometric measurements, which included body, thorax, and the head sizing of each dog, have been investigated to establish the association with heart murmur intensity, valvular and annular echocardiographic measurements, MVP and regurgitant jet size using inverse probability weighting (IPW) analyses to adjust for confounding. The IPW analyses showed that when head length and nose length decreased, dogs had more severe regurgitant jet size. Furthermore, subjects with more pronounced head stop angle had thicker anterior mitral valve leaflets. A brachycephalic morphotype, with dogs more similar to King Charles Spaniel breed in cephalic morphology, is associated with a more severe regurgitant jet size and with valvular characteristics related to worse forms of MMVD.

The epidemiology of Congenital Heart Diseases (CHDs) has changed over the past twenty years. This study aimed to evaluate the prevalence of CHDs in the population of dogs recruited in a single referral center (RC); compare the epidemiological features of CHDs in screened breeds (Boxers) versus non-screened (French and English Bulldogs, German Shepherds); investigate the association of breeds with the prevalence of CHDs; determine the popularity and volatility of breeds over a 20-year period; analysed the trends of the most popular breeds in the overall population of new-born dogs registered in the Italian Kennel Club (IKC) from 1st January 1997 to 31st December 2017. The RC's cardiological database was analysed, and 1,779 clinical records were included in a retrospective observation study. Descriptive statistics and frequencies regarding the most representative breeds and CHDs were generated. A logistic regression model was used to analyse the trends of the most common CHDs found in single and in cluster of breeds. The relationship between breed popularity and presence of CHDs was studied. The most common CHDs were Pulmonic Stenosis, Patent Ductus Arteriosus, Subaortic Stenosis, Ventricular Septal Defect, Aortic Stenosis, Tricuspid Dysplasia, Atrial Septal Defect, Double Chamber Right Ventricle, Mitral Dysplasia, and others less frequent. The most represented pure breeds were Boxer, German Shepherd, French Bulldog, English Bulldog, Maltese, Newfoundland, Rottweiler, Golden Retriever, Chihuahua, and others in lower percentage. Chihuahuas, American Staffordshire Terriers, Border Collies, French Bulldogs, and Cavalier King Charles Spaniel were the most appreciated all of which showed a high value of volatility. This study found evidence for the value of the screening program implemented in Boxers; fashions and trends influence dog owners' choices more than the worries of health problems in a breed. Effective breeding programs are needed in order to control the diffusion of CHDs without impoverishing the genetic pool.

To solve the problem of vascular access failure, a novel semi-degradable hybrid vascular graft, manufactured by electrospinning using silk fibroin and polyurethane (Silkothane), has been previously developed and characterized in vitro. This proof-of-concept animal study aims at evaluating the performances of Silkothane grafts in a sheep model of arteriovenous shunt, in terms of patency and short-term remodeling. Nine Silkothane grafts are implanted between the common carotid artery and the external jugular vein of nine sheep, examined by palpation three times per week, by echo-color Doppler every two weeks, and euthanized at 30, 60, and 90 days (N = 3 per group). At sacrifice, grafts are harvested and submitted for histopathology and/or scanning electron microcopy (SEM). No cases of graft-related complications are recorded. Eight of nine sheep (89%) show 100% primary unassisted patency at the respective time of sacrifice (flow rate 1.76 ± 0.61 L min-1 , one case of surgery-related thrombosis excluded). Histopathology and SEM analysis evidence signs of inflammation and pseudointima inside the graft lumen, especially at the venous anastomosis; however, endoluminal stenosis never impairs the functionality of the shunt and coverage by endothelial cells is observed. In this model, Silkothane grafts grant safety and 100% patency up to 90 days.

The epidemiology of Congenital Heart Diseases (CHDs) has changed over the past twenty years.We evaluated the prevalence of CHDs in the population of dogs recruited in a single referral center (RC); compared the epidemiological features of CHDs in screened breeds (Boxers) versus nonscreened (French and English Bulldogs and German Shepherds), investigated the association of breeds with the prevalence of CHDs, determined the popularity and volatility of breeds over a 20-year period; and analysed the trends of the most popular breeds in the overall population of new-born dogs registered in the Italian Kennel Club from 1st January 1997 to 31st December 2017.This was a retrospective observational study, the cardiological database of the RC was analysed, and 1,779 clinical records fulfilled the inclusion criteria.Descriptive statistics and frequencies regarding the most representative breeds and CHDs were generated. A logistic regression model was used to analyse the trends of the most common CHDs found in single breeds (French Bulldog, English Bulldog, Boxer, and German Shepherd), and in groups of breeds (brachycephalic breeds and the most represented large breeds). The relationships between the breed popularity and the presence of CHDs was studied.The most common CHDs were Pulmonic Stenosis (34,1%), Patent Ductus Arteriosus (26,4%), Subaortic Stenosis (14,6%), Ventricular Septal Defect (4,8%), Aortic Stenosis (4,7%), Tricuspid Dysplasia (3,4%), Atrial Septal Defect (1,9%), Double Chamber Right ventricle (1,8%), Mitral Dysplasia (1,6%), and reverse Patent Ductus Arteriosus (0,7%). The most represented pure breeds were Boxer (19,4%), German Shepherd (9,4%), French Bulldog (6,2%), English Bulldog (4,9%), Maltese (3,7%), Newfoundland (3,1%), Rottweiler (3,1%), Golden Retriever (3,0%), Chihuahua (2,8%), Poodle (2,5%), Cavalier King Charles Spaniel (2,2%), American Staffordshire Terrier (2,1%), Labrador Retriever (2,3%), Dobermann (2,1%), Miniature Pinscher (2,0%), Cocker Spaniel (2,0%), Yorkshire Terrier (1,7%), Dogue de Bordeaux (1,6%), Dachshund (1,6%), and Bull Terrier (1,5%). Chihuahuas, American Staffordshire Terriers, Border Collies, French Bulldogs, and Cavalier King Charles Spaniel were the most appreciated small and medium breeds, all of which showed a high value of volatility.In conclusion, this study found evidence for the value of the screening program implemented in Boxers, which decreased the prevalence of Subaortic Stenosis and Pulmonic Stenosis. However, fashions and trends influence dog owners’ choices more than the worries of health problems frequently found in a breed. Effective breeding programs are needed in order to control the diffusion of CHDs without impoverishing the genetic pool; in addition, dog owners should be educated, and the breeders supported by a network of veterinary cardiology centers.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

BACKGROUND In an attempt at answering the need for a valuable and durable hemodialysis vascular access, a novel semi‐degradable hybrid vascular graft, manufactured by electrospinning using silk fibroin and polyurethane (Silkothane®), has been developed and characterized in vitro according to standards. OBJECTIVES In this proof‐of‐principle animal study, we aimed at evaluating the performances of Silkothane® grafts in a sheep model of arteriovenous shunt, with respect to patency and short‐term graft remodeling. MATERIALS AND METHODS Nine Silkothane® grafts (6mm inner diameter, ≈7cm long, ≈400μm thick) were surgically placed into the left cervical fossa of nine female sheep, between the common carotid artery and the external jugular vein. During the housing period the animals were treated with an inhibitor of platelets aggregation. Grafts were examined by palpation three times per week, and by duplex ultrasound every two weeks to exclude significant stenosis, dilation, presence of thromboses, neointimal proliferation or other complicating features. The sheep were euthanized at 30, 60 and 90 days (N=3 for each group). At sacrifice, grafts were harvested, fixed, and submitted for histologic, immunohistochemical and Scanning Electron Microscopy examination. RESULTS No cases of graft‐related complications (e.g. seroma formation, transgraft bleeding, aneurismal dilation, calcification, structural yielding) were recorded in this study. One graft failed due to a thrombotic event likely related to a technical error (11%). One sheep had post‐operative wound infection, surgically resolved (11%). Four out of nine sheep (44%) showed post‐operative edema, usually disappearing in 7 days. Eight of nine sheep (89%) showed 100% primary unassisted patency at the respective time of sacrifice, as confirmed by palpation and ultrasound evaluation (average flow rate 1.76 ± 0.61 l/min). Histological, immunoistochemical and SEM analysis evidenced signs of inflammation and formation of neointimal hyperplasia at the venous anastomosis, as it typically happens with arteriovenous fistulae and synthetic grafts. CONCLUSIONS In our ovine model of arteriovenous shunt, Silkothane® grafts provided evidences of safety and efficacy in granting 100% patency up to 90 days. Further studied need to be conducted in order to directly compare the novel grafts with commercially available synthetic grafts.