Clinical presentation, management, and survival in dogs with persistent atrial standstill in the United Kingdom.

OBJECTIVES: To investigate the clinical and echocardiographic presentation of dogs with persistent atrial standstill (PAS), identify variables measured at first presentation that could predict their survival, and document the progression of the disease after pacing. MATERIALS AND METHODS: Retrospective study of medical records of dogs diagnosed with PAS at three referral hospitals of the United Kingdom over seven years. RESULTS: Twenty-six dogs were diagnosed with PAS during the study period. Median age of the population was three years (range: seven months-12.5 years). The most common clinical sign was syncope (14/26). Twenty-four dogs received artificial pacemakers (PM). Major complications after PM implantation were observed in four dogs (four/24). Serial echocardiographic examinations showed that cardiac dimensions of PAS dogs with left atrial or left ventricular dilation at first presentation did not return to reference range after pacing. Further dilation of the cardiac chambers, recurrence of congestive heart failure (CHF), or development of new episodes of CHF were documented in seven, four, and 10 PAS dogs, respectively, despite pacing. Median survival time for cardiac-related deaths after PM implantation was 1512 days (18-3207). Neither CHF nor echocardiographic variables at presentation predicted survival after PM implantation in PAS dogs. CONCLUSIONS: Persistent atrial standstill (PAS) is an uncommon bradyarrhythmia, occurring in young adult dogs. Affected dogs were often presented with syncope. Whilst syncope resolved, cardiac remodeling persisted after PM implantation. Long-term survival was favorable after PM implantation and was not predicted by congestive status or cardiac chamber size at first presentation.

Validation of heart rate spot-check protocol to measure circadian variation and heart rate in healthy dogs and dogs with atrial fibrillation.

INTRODUCTION: Alternatives for out-of-clinic heart rate (HR) measurement are required to optimise the management of atrial fibrillation (AF) in dogs. Additionally, the presence of circadian variation (CV) in HR in pet dogs remains unknown. We aimed to identify the number and duration of spot-checks required for an accurate estimation of 24-hour HR in canine AF. Circadian variation in HR was examined in healthy dogs and dogs with AF, and spot-check-derived HR was compared with a CV-derived gold standard. MATERIALS AND METHODS: Ambulatory electrocardiogram data from healthy dogs and dogs with AF were retrospectively analysed. Heart rate was calculated from the entire recording and pre-defined periods (spot-checks) of one hour to 30 and 60 s in duration. Circadian variation in HR was determined by cosinor analysis. Bias and limits of agreement of means and median HR with mesor HR were determined by correlation and Bland-Altman analysis. RESULTS: Circadian variation in HR was identified not only in 18/22 healthy dogs and 14/21 AF dogs but only on ambulatory electrocardiogram recordings. Four-hourly spot-checks provided the most accurate estimate of mesor HR in healthy dogs (bias of the median over 30 s 7.70, limits of agreement 7.48), whereas, in dogs with AF, four, six and eight-hourly spot-checks provided reliable estimates of mesor HR (bias within -1.29 and -29.5). CONCLUSIONS: Four, six and eight-hourly HR spot-checks can estimate 24-hourly HR in dogs with AF. There was CV in HR in most healthy pet dogs and dogs with AF. Spot-check protocols cannot identify CV in HR.

Outcome clinical audit: analyses of interventional closure of patent ductus arteriosus in dogs.

OBJECTIVES: The objectives of this study were to determine whether conducting a clinical audit was achievable in a group of centres that perform interventional cardiac procedures and to report the success and complications rates in dogs diagnosed with patent ductus arteriosus. METHODS: This was a multicentre, European-wide, prospective study. Patient data were entered into a bespoke database prior to commencing interventional closure of patent ductus arteriosus in all animals undergoing this procedure during the study period. The database was designed to gather clinical audit information, after completion of the procedure, such as discharge outcome, complication rate, and medium-term outcome. RESULTS: A total of 339 cases were included from five participating centres. The process of performing clinical audit was achieved in all centres. Successful discharge outcome was 95.9% with a complication rate of 4.1%. The procedure-related mortality was 0.6%. 149 cases (43.9%) were either lost to follow-up or had not yet had a follow-up within the time period. Of the remaining 169 cases in which follow-up was available, 157 (92.9%) cases had a successful medium-term outcome CONCLUSIONS: This study demonstrates that the process of performing a clinical audit is achievable in veterinary clinical interventions across different centres. These results provide a benchmark for future comparison in our ongoing clinical audit and validate the process of clinical audit for other centres performing cardiac interventions. The use of clinical audit should be considered in other aspects of veterinary medicine.

Non-cardiogenic pulmonary oedema complicating balloon valvuloplasty and stent angioplasty of severe pulmonary valve stenosis in four dogs.

In dogs, balloon valvuloplasty is considered the treatment of choice for severe pulmonary valve stenosis, and this technique is currently performed routinely in specialist referral practices with low morbidity and mortality. Stent angioplasty has also been recently proposed as a viable treatment option. The present case series describes the clinical course of four dogs with severe pulmonary valve stenosis, treated with balloon valvuloplasty or stent angioplasty at four different institutions, which developed non-cardiogenic pulmonary oedema perioperatively after apparently successful dilation of the pulmonary valve. In three cases, there was evidence of some degree of pulmonary hypertension before ballooning. Despite intensive care, the complication proved fatal in three cases. Clinicians should therefore be aware of this life-threatening complication, previously undescribed in dogs.

Eosinophilic pericardial effusion in a cat with complex systemic disease and associated peripheral eosinophilia.

An 11-year-old domestic shorthair cat was referred for investigation of dry cough of 1-week duration and cardiomegaly. Echocardiography revealed pericardial effusion, and eosinophils were identified as the predominant cell type in fluid collected by pericardiocentesis. Thoracic computed tomography imaging and bronchoscopy were supportive of mild lower airway disease, while bronchoalveolar lavage confirmed eosinophilic inflammation and concurrent Mycoplasma felis infection. A few months after the initial presentation, there was clinical deterioration, and further investigation suggested intestinal lymphoma. It was hypothesized that pericardial effusion and lower airway inflammation were an early manifestation of hypereosinophilic syndrome, possibly as a paraneoplastic consequence of lymphoma.

Aortic sinus aneurysm communicating with the main pulmonary artery, and a concurrent patent ductus arteriosus, in a dog.

This is the first report of an aortic sinus aneurysm with a communication to the main pulmonary artery, resulting in left-to-right shunting, diagnosed in vivo in a dog. There was also a second left-to-right shunt through a patent ductus arteriosus. Computed tomography (CT) angiography was used to confirm both congenital anomalies and assess the relative contributions of the two left-to-right shunts to left-sided volume overload.

Spontaneous torsade de pointes and ventricular fibrillation in a dog during pacemaker implantation.

Torsade de pointes is an unusual complication seen in dogs during pacemaker implantation, although ventricular fibrillation has been previously reported. This case report describes torsade de pointes in a dog during pacemaker implantation that degenerated into ventricular fibrillation and discusses the possible contributory factors. It also illustrates the relevance of a pre-emptive resuscitation plan and how this might have affected the outcome in the patient.

Glucocorticoid metabolism and the action of 11 beta-hydroxysteroid dehydrogenase 2 in canine congestive heart failure.

The enzyme 11-beta-hydroxysteroid dehydrogenase isoenzyme 2 (11BHSD2) is responsible for converting the active glucocorticoid cortisol to inactive cortisone and in the renal medulla protects the mineralocorticoid receptor (MR) from activation by cortisol. Derangements in 11BHSD2 activity can result in reduced conversion of cortisol to cortisone, activation of the MR by cortisol and, consequently, sodium and water retention. The objective of this study was to examine glucocorticoid metabolism in canine congestive heart failure (CHF), specifically to evaluate whether renal 11BHSD2 activity and expression were altered. Dogs were prospectively recruited into one of two phases; the first phase (n=56) utilized gas chromatography-tandem mass spectrometry to examine steroid hormone metabolites normalised to creatinine in home-caught urine samples. Total serum cortisol was also evaluated. The second phase consisted of dogs (n=18) euthanased for refractory CHF or for behavioural reasons. Tissue was collected from the renal medulla for examination by quantitative reverse transcription polymerase chain reaction, immunohistochemistry and protein immune-blotting. Heart failure did not change urinary cortisol:cortisone ratio (P=0.388), or modify renal expression (P=0.303), translation (P=0.427) or distribution of 11BHSD2 (P=0.325). However, CHF did increase excretion of 5α-tetrahydrocortisone (P=0.004), α-cortol (P=0.002) and α-cortolone (P=0.009). Congestive heart failure modifies glucocorticoid metabolism in dogs by increasing 5α-reductase and 20α-hydroxysteroid dehydrogenase activity. Differences between groups in age, sex and underlying disease processes may have influenced these results. However, 11BHSD2 does not appear to be a potential therapeutic target in canine CHF.

Total anomalous pulmonary venous connection in a mature dog.

A 2-year 10-month, male neutered, crossbreed dog presented for evaluation of cyanosis and exercise intolerance. Doppler echocardiography revealed severe dilation of the right atrium and right ventricle with moderate pulmonary hypertension. Right-to-left shunting across a large ostium secundum atrial septal defect was confirmed by contrast echocardiography. Thoracic radiography revealed a vascular pattern together with cardiomegaly. Computed tomography angiography identified an anomalous pulmonary venous connection in which all pulmonary veins, apart from the right middle vein, coalesced into a single, large aneurysmal vein that then drained into the right atrium via the cranial vena cava. The distal opening of the right middle pulmonary vein could not be determined. A presumptive diagnosis of partial anomalous pulmonary venous connection was made. The dog was medically managed with sildenafil (1.5 mg/kg by mouth [PO] every 8 h) and remained clinically stable for 2 months before euthanasia due to worsening exercise intolerance. On postmortem examination, all pulmonary veins, including the right middle vein, were shown to communicate with a single, large central vein. This large vein then connected with the right atrium via the cranial vena cava, consistent with a total anomalous pulmonary venous connection. This case report describes a rare congenital abnormality which has not been previously reported in a mature dog.

Poincaré plots as a measure of heart rate variability in healthy dogs.

INTRODUCTION: Poincaré plots remain largely unused for heart rate variability (HRV) analysis in dogs. The aims of this study were to describe, qualitatively and quantitatively, Poincaré plots in healthy dogs, to compare them with other methods of HRV analysis, to assess their day-to-day variability and to investigate the effect of activity on the plots. ANIMALS: Twenty-five healthy dogs. METHODS: Poincaré plots, their standard descriptors, and other measures of HRV were generated from 24-hour ambulatory electrocardiographic recordings and 6 hours of rest and activity. RESULTS: The 24-hour Poincaré plot demonstrated a 'Y' pattern. The arms of the 'Y' were derived mostly from periods of rest and activity populated the stalk. The quantitative descriptors of the plot had strong correlations in the time-domain, with weaker correlations in the frequency-domain. Individuals showed low day-to-day variability of the plot pattern and of the standard deviation of points along the major axis of the plot (SD2), which measures overall HRV. Day-to-day variability was higher for the standard deviation of points perpendicular to the major axis of the plot (SD1), which is a measure of short-term HRV, and for the SD1/SD2 ratio. CONCLUSIONS: Twenty-four-hour Poincaré plots in healthy dogs show a 'Y' pattern with subtle variations unique to the individual. The amount of activity and rest within the recording has a significant effect on the plot. Quantitative analysis of the plot can be used as a surrogate for time-domain analysis of HRV but visual analysis of the pattern provides additional information.

Comparison of cellular changes in Cavalier King Charles spaniel and mixed breed dogs with myxomatous mitral valve disease.

INTRODUCTION: The aim of this study was to determine if there are differences in cellular changes in Cavalier King Charles spaniel (CKCS) myxomatous mitral valves compared to non-CKCS dogs. ANIMALS: Cavalier King Charles spaniels (n = 6) and age-matched mixed breed (n = 6) with severe myxomatous mitral valve disease (MMVD), and normal mixed breed (n = 4) dogs. MATERIALS AND METHODS: Immunohistochemistry staining and qualitative and quantitative analysis of mitral valves sections, examining for the presence of CD11c and CD45, vimentin, alpha smooth muscle actin (α-SMA) and embryonic smooth muscle myosin heavy chain (Smemb), von Willebrand factor and CD31 and Ki-67. RESULTS: Vimentin positive cell numbers were increased in the MMVD dogs and distributed throughout the valve with greatest density close to the endothelium. There were no significant differences in cell marker expression for the two diseased groups, but cell numbers were significantly increased compared to controls for α-SMA (CKCS only) and Smemb (CKCS and mixed breed: p < 0.05). Alpha smooth muscle actin+ cells were primarily located at the valve edge, with Smemb+ cells similarly located, but also present throughout the valve stroma. A small number of cells close to the valve edge co-expressed α-SMA and Smemb. Endothelial von Willebrand factor expression was identified in all valves, with evidence of disrupted endothelium in the diseased, but was also found in diseased valve stroma. There was no staining for CD11c, CD45 or CD31 in any valve. Ki-67+ cells formed linear clusters at the leaflet tip and were sparsely distributed throughout both myxomatous valve groups. CONCLUSIONS: The cellular changes notes with advanced stage MMVD appear similar for CKCS when compared to mixed breed dogs.

Gene network and canonical pathway analysis in canine myxomatous mitral valve disease: a microarray study.

Myxomatous mitral valve disease (MMVD) is the single most common acquired heart disease of the dog and is particularly common in small pedigree breed dogs such as the Cavalier King Charles spaniel (CKCS). There are limited data on the mitral valve transcriptome and the aim of this study was to use the microarray technology in conjunction with bioinformatics platforms to analyse transcript changes in MMVD in CKCS compared to normal dogs (non-CKCS). Differentially expressed genes (n = 5397) were identified using cut-off settings of fold change, false discovery rate (FDR) and P <0.05. In total, 4002 genes were annotated to a specific transcript in the Affymetrix canine database, and after further filtering, 591 annotated canine genes were identified: 322 (55%) were up-regulated and 269 (45%) were down-regulated. Canine microRNAs (cfa-miR; n = 59) were also identified. Gene ontology and network analysis platforms identified between six and 10 significantly different biological function clusters from which the following were selected as relevant to MMVD: inflammation, cell movement, cardiovascular development, extracellular matrix organisation and epithelial-to-mesenchymal (EMT) transition. Ingenuity Pathway Analysis identified three canonical pathways relevant to MMVD: caveolar-mediated endocytosis, remodelling of epithelial adherens junctions, and endothelin-1 signalling. Considering the biological relevance to MMVD, the gene families of importance with significant difference between groups included collagens, ADAMTS peptidases, proteoglycans, matrix metalloproteinases (MMPs) and their inhibitors, basement membrane components, cathepsin S, integrins, tight junction cell adhesion proteins, cadherins, other matrix-associated proteins, and members of the serotonin (5-HT)/transforming growth factor -ß signalling pathway.

Cell maceration scanning electron microscopy and computer-derived porosity measurements in assessment of connective tissue microstructure changes in the canine myxomatous mitral valve.

Canine myxomatous mitral valve disease is associated with changes in the valve extracellular matrix (ECM). The aim of this study was to examine the use of cell macerated scanning electron microscopy (CMSEM) in evaluating ECM changes in a small sample of valves and to quantify these changes using computer-aided image analysis of sample porosity (a measure of structural disorganisation and collagen loss). The distinct layered structure of the de-cellularised matrix could be seen in the normal valve and there were marked changes in layers and ECM organisation as the disease progressed. Clearly visible and quantifiable, statistically significant changes were found in valve porosity across the entire leaflet thickness and particularly in the valve mid and distal zones. All of these changes are presumed to affect the mechanical function of the valve. In conclusion, CMSEM with computed image analysis can be used to visualise and measure tissue structural changes in a quasi-3-dimensional manner in normal and diseased tissues.

Morphological changes to endothelial and interstitial cells and to the extra-cellular matrix in canine myxomatous mitral valve disease (endocardiosis).

Morphological and functional changes in endothelial and interstitial cells are considered central to myxomatous degeneration of the canine mitral valve (endocardiosis). The aim of this study was to describe and quantify changes in valve endothelial cells (VECs), interstitial cells (VICs) and the extra-cellular matrix (ECM) of the sub-endothelial zone of diseased valves using a combination of transmission electron microscopy, stereology and computer-aided image analysis. Marked degradation of the endothelium was evident in diseased valves, which coincided with significant degradation of the local ECM (P<0.001). There were decreases and increases in the numbers of VECs and VICs, respectively, in diseased valves, with particular accumulation of VICs subjacent to the valve surface (P<0.01). Overall, VICs were more pleomorphic than VECs in both normal and diseased valves, but for VECs, the degree of pleomorphism was significantly different in diseased valves (P<0.0001). The findings of the study confirm that canine myxomatous mitral valve disease is associated with marked endothelial damage, with attendant proliferation of subjacent activated myofibroblasts. The fact that similar endothelial changes are present in normal valves suggests these processes not only contribute to valve pathology, but may also represent life-long valve remodelling.

Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study).

BACKGROUND: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported. HYPOTHESIS: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival. ANIMALS: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America. METHODS: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo. The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint. RESULTS: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441-1152 days) versus the placebo group (441 days, IQR 151-641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491-1531 days) versus the placebo group (466 days, IQR 236-710 days) (log-rank P = .034). CONCLUSION AND CLINICAL IMPORTANCE: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.

Canine tissue-specific expression of multiple small leucine rich proteoglycans.

Small leucine rich proteoglycans (SLRPs) are important constituents of extracellular matrix (ECM) and contribute to the production, organization and remodelling of collagen and elastin through complex biological systems. The relative expression and distribution of SLRPs in a variety of different mammalian tissues is poorly characterized. The aim of this study was to map the expression of seven SLRPs (biglycan, versican, prolargin, fibromodulin, osteoglycin, decorin and lumican) in seven tissues (bone, cartilage, cruciate ligament, skin, ventricular myocardium, mitral valve and cornea) in young adult dogs using a combination of quantitative real-time PCR, immunohistochemistry and protein immunoblotting. Clear and consistent patterns of SLRP expression and distribution were identified for the seven tissues examined, with the greatest SLRP expression in cartilage, skin, cornea and mitral valve, and the least expression in myocardium. In general, lumican and prolargin had the greatest expression across the seven tissues whilst osteoglycin was the least abundantly expressed SLRP. These data provide a SLRP profile for different canine tissues which can inform future studies of SLRP expression in development and disease.

Outcome in 55 dogs with pulmonic stenosis that did not undergo balloon valvuloplasty or surgery.

OBJECTIVE: To determine the outcome, independent predictors of cardiac death, and the Doppler-derived pressure gradient cut-off for predicting cardiac death in dogs with pulmonic stenosis, with or without tricuspid regurgitation, that do not undergo balloon valvuloplasty or valve surgery. METHODS: Review of medical records of two UK referral centres between July 1997 and October 2008 for all cases of pulmonic stenosis that had no balloon valvuloplasty or valve surgery. Inclusion criteria included a diagnosis of pulmonic stenosis; spectral Doppler pulmonic velocity greater than 1·6 m/s; characteristic valve leaflet morphological abnormalities. Exclusion criteria included concurrent significant cardiac defects, including tricuspid dysplasia. Dogs with tricuspid regurgitation were included. Dogs were classified according to Doppler-derived pressure gradients into mild, moderate or severe pulmonic stenosis categories. RESULTS: Presence of tricuspid regurgitation and severe stenosis were independent predictors of cardiac death. A pulmonic pressure gradient of more than 60 mmHg was associated with 86% sensitivity, and 71% specificity of predicting cardiac death. CLINICAL SIGNIFICANCE: There is an increased probability of cardiac death in those cases which have a pulmonary pressure gradient greater than 60 mmHg and tricuspid regurgitation, though the effect of severity of tricuspid regurgitation on outcome was not measurable because of small sample sizes. These animals might benefit from intervention.

The vasovagal tonus index as a prognostic indicator in dogs with dilated cardiomyopathy.

OBJECTIVES: To investigate the prognostic and diagnostic value of heart rate variability (HRV) using the vasovagal tonus index (VVTI) in dogs suffering from idiopathic dilated cardiomyopathy (DCM). METHODS: Electrocardiographic (ECG) recordings of 369 patients presented to a referral centre between 1993 and 2006 were reviewed. RESULTS: VVTI values were calculated from 132 dogs. Lower VVTI values were found in patients in International Small Animal Cardiac Health Council (ISACHC) heart failure (HF) class 2 and 3 compared with class 1. VVTI was found to be positively correlated with survival time (ST) in class 2 and 3 patients. When a cut-off value of 7.59 for VVTI was used, the test could differentiate patients in ISACHC HF class 1 versus 2 and 3 with a sensitivity of 89 per cent and a specificity of 62.5 per cent. The ST for patients with VVTI values less than 7.59 was significantly lower. CLINICAL SIGNIFICANCE: The VVTI is a useful index, obtained from a standard ECG recording that estimates HRV in dogs and does not require any specific equipment for its calculation. It can be useful as a diagnostic tool to assess the severity of HF and is a useful prognostic tool in dogs with DCM.