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Abstract Background No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. Objectives To evaluate an activated clotting time (ACT)‐based heparin dose‐response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin – ACT and in vitro heparin – factor anti‐Xa activity (anti‐Xa) relationships in dogs. Methods Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0‐0.5‐1‐2‐4 international unit (IU)/mL) was prepared and ACT and anti‐Xa were determined using whole blood and frozen plasma, respectively. Results The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti‐Xa increased significantly with increasing blood heparin concentration. Heparin – ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin – anti‐Xa remained linear throughout the tested range. Conclusions The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin – ACT relationship, as observed in vitro. Anti‐Xa is a promising alternative for ACT; however, unavailability as a point‐of‐care test and lack of in vivo target values restrict its current use.

Abstract Background Activated clotting times (ACTs) are used to screen for coagulopathies and monitor heparin therapy. Objectives To determine a reference interval (RI) for ACT in dogs using a point‐of‐care analyser, to quantify intra‐subject within‐ and between‐day variability, to quantify analyser reliability and inter‐analyser agreement and to study the influence of a delay in measurement. Methods Forty‐two healthy dogs were included. Measurements were performed on fresh venous blood using the i‐STAT 1 analyser. The RI was determined using the Robust method. Intra‐subject within‐day variability and between‐day variability were quantified between baseline and 2 h (n = 8) or 48 h (n = 10) later. Analyser reliability and inter‐analyser agreement were studied by duplicate measurements (n = 8) on identical analysers. The influence of measurement delay was studied before and after a delay of one analytical run (n = 6). Results Mean, lower and upper reference limits for ACT were 92.9 ± 9.1, 74.4 and 111.2 s, respectively. Coefficients of variation of intra‐subject within‐ and between‐day variability were 8.1% and 10.4%, respectively, resulting in a significant between‐day measurement difference. Analyser reliability assessed by the intraclass correlation coefficient and coefficient of variation were 0.87% and 3.3%, respectively. Significantly lower ACT values were observed after a measurement delay compared to direct analysis. Conclusions Our study provides an RI for ACT in healthy dogs using the i‐STAT 1 and suggests low intra‐subject within‐ and between‐day variability. Analyser reliability and inter‐analyser agreement were good; however, analysis delay and between‐day differences could significantly influence ACT results.

Combretastatin A4-phosphate (CA4P) is a vascular disrupting agent that was recently described for the treatment of solid canine tumors. Conventional echocardiography and pulsed wave tissue Doppler imaging did not reveal cardiotoxicity in dogs, however, the gold standard for assessing myocardial damage in humans receiving cardiotoxic chemotherapeutics is two-dimensional speckle-tracking echocardiography. The current study evaluated the cardiotoxic effect of a single dose of CA4P in dogs using peak systolic strain measurements and the variability of these measurements. Echocardiographic examinations of seven healthy beagles and five canine cancer patients that received CA4P were retrospectively reviewed. Peak systolic regional longitudinal strain (LSt), peak systolic regional circumferential strain (CSt), and peak systolic regional radial strain (RSt) were measured before and 24 h after administration of CA4P. Peak systolic strain measurements were compared to serum cardiac troponin I (cTnI). To quantify intra- and inter-observer measurement variability, seven echocardiographic examinations were selected and each strain parameter was measured by three observers on three consecutive days. After CA4P administration, the median LSt and CSt values decreased by 21.8% (p = 0.0005) and 12.3% (p = 0.002), respectively, whereas the median RSt values were not significantly different (p = 0.70). The decrease in LSt was correlated with increased serum cTnI values (Spearman rho = −0.64, p = 0.02). The intra-observer coefficients of variation (CV) were 9%, 4%, and 13% for LSt, CSt, and RSt, respectively, while the corresponding interobserver CVs were 11%, 12%, and 20%. Our results suggest that regional peak systolic strain measurements may be useful for the early detection of cardiotoxicity that is caused by vascular disrupting agents and that LSt may be promising for the follow-up of canine cancer patients.

Background: No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. Objectives: To evaluate an activated clotting time (ACT)‐based heparin dose‐response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin – ACT and in vitro heparin – factor anti‐Xa activity (anti‐Xa) relationships in dogs. Methods: Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0‐0.5‐1‐2‐4 international unit (IU)/mL) was prepared and ACT and anti‐Xa were determined using whole blood and frozen plasma, respectively. Results: The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti‐Xa increased significantly with increasing blood heparin concentration. Heparin – ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin – anti‐Xa remained linear throughout the tested range. Conclusions: The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin – ACT relationship, as observed in vitro. Anti‐Xa is a promising alternative for ACT; however, unavailability as a point‐of‐care test and lack of in vivo target values restrict its current use. [ABSTRACT FROM AUTHOR]

A one-year-and-seven-month-old, 28 kg, male castrated crossbreed dog was presented for supraventricular tachycardia causing recurrent episodes of anorexia and lethargy. Sotalol (2.2 mg/kg q12 h) reduced the frequency of symptomatic episodes but did not provide full relief. Three-dimensional electroanatomical mapping was performed at the Ghent University Small Animal Teaching hospital using the CARTO 3. Right atrial activation mapping identified the earliest atrial activation right posteroseptal, near the tricuspid annulus. Fast retrograde ventriculoatrial conduction during tachycardia and extrastimulus testing confirmed the presence of a concealed right posteroseptal accessory pathway. Six radiofrequency catheter ablation applications were delivered, and tachycardia remained uninducible. The dog recovered well from the procedure. Sotalol was stopped three weeks later, and no more clinical signs were noted by the owner. Repeated 24-hour electrocardiography monitoring on day one and at one, three, and 12 months after the procedure showed no recurrence of tachycardia. [ABSTRACT FROM AUTHOR]

A 7-week-old male Doberman presented with tachypnea, dyspnea and a VI/VI, left cranial, continuous heart murmur. Thoracic radiographs revealed severe left-sided cardiomegaly, presence of a rounded soft tissue opacity in the caudodorsal aspect of the thoracic cavity and signs of left-sided congestive heart failure. Clinical signs of heart failure were medically controlled. Echocardiography and computed tomography demonstrated a left-to-right shunting patent ductus arteriosus (PDA) in combination with a right-to-left shunting pulmonary arteriovenous malformation (PAVM) between the right main pulmonary artery and the right caudal pulmonary vein. Arterial blood gasses revealed mild hypoxemia. Transcatheter occlusion of the PDA using an Amplatz Canine Duct Occluder was performed. Four months post-operatively, echocardiography showed normal cardiac size and function with complete PDA closure. Thoracic radiographs revealed absence of the rounded opacity and resolution of cardiomegaly and vascular congestion. The PAVM was no longer visualized on repeated computed tomography and the arterial blood gasses were within normal limits. A PAVM connecting a pulmonary artery to a pulmonary vein has only rarely been reported in dogs. This report describes the presence of a congenital PAVM in combination with a PDA in a dog, which has not been previously reported in veterinary medicine. [ABSTRACT FROM AUTHOR]

A two-year and four-month, male German Shepherd was referred for exercise intolerance and panting. Irregular heart auscultation (250 beats per minute (bpm)) and pulse deficits were noted on physical exam. Electrocardiogram (ECG) showed irregular, narrow-QRS tachycardia without P waves compatible with coarse atrial fibrillation (AF). A 24-h ECG showed sustained AF (mean ventricular response rate 92 bpm). Echocardiography showed no structural abnormalities. Given the young age and presence of AF-related symptoms, rhythm control was preferred. Transthoracic electrical cardioversion was successfully performed six weeks later but AF recurred within 24-h. Sotalol was started but discontinued due to poor tolerance and AF persisted. Seven months after AF diagnosis, radiofrequency catheter ablation (RFCA) aiming for pulmonary vein isolation was performed under general anaesthesia. After transseptal puncture, three-dimensional electroanatomical mapping of the left atrium was performed. Point-by-point pulmonary vein isolation was achieved by RFCA. Seventy-eight RFCA lesions were placed in the left atrium encircling the three pulmonary vein ostia followed by electrical cardioversion. No complications occurred and the dog was discharged with amiodarone. In the immediate post-operative phase, there was recurrence of persistent AF requiring electrical cardioversion. Furthermore, at one month after the ablation, the dog experienced a single and transient paroxysm of AF. Since then, stable sinus rhythm (SR) was retained on daily ECG monitoring at home and confirmed by 24-h ECG three months post-operatively. Amiodarone was stopped subsequently. At the time of writing (one year post-operative), the dog remains in SR with normal exercise tolerance. [ABSTRACT FROM AUTHOR]

A four-month-old male Shetland Sheepdog presented with exercise intolerance. Physical examination revealed an IV/VI left cranial systolic heart murmur. Echocardiography showed a severe infundibular pulmonic stenosis and a concomitant restrictive ventricular septal defect. As clinical signs of congestive right-sided heart failure worsened and were refractory to medical treatment, surgical correction was advised. Via sternotomy, with cardiopulmonary bypass and cardioplegic cardiac arrest, ventricular septal defect closure and resection of the stenotic infundibular band were performed through right ventriculotomy, followed by patch enlargement. Postoperative recovery was uneventful and echocardiography showed complete resolution of the stenosis and successful closure of the ventricular septal defect. Follow-up echocardiography revealed restenosis after seven weeks and recurrence of right-sided heart failure three months postoperatively. Stenting of the restenosis was attempted via a hybrid procedure with sternotomy and direct transventricular approach. The dog developed fatal ventricular fibrillation during stent deployment. This is the first dog in which surgical right ventricular patch enlargement under cardiopulmonary bypass is reported for the treatment of a primary infundibular pulmonic stenosis. [ABSTRACT FROM AUTHOR]

Three-dimensional electroanatomical mapping (3D EAM) has expanded radiofrequency catheter ablation applications in humans to almost all complex arrhythmias and has drastically reduced fluoroscopy use, yet its potential in dogs is poorly investigated. The objectives of the current study were to assess the feasibility and safety of 3D EAM of all four heart chambers, 3D EAM-guided biopsies and transseptal puncture in dogs. Eight healthy purpose-bred Beagle dogs. Electroanatomical mapping was performed under general anaesthesia during sinus rhythm using a 22-electrode mapping catheter. Left heart catheterisation was achieved by either retrograde transaortic access (n = 4) or transseptal puncture (n = 4). Successful 3D EAM of the right atrium and ventricle was achieved in all dogs at a median time of 33 (13–40) min and 17 (3–52) min, respectively. Left atrial and ventricular 3D EAM was successful in six and seven dogs, at a median time of 17 (4–27) min and 8 min (4–19 min), respectively. Complications requiring intervention occurred in one dog only and were a transient third degree atrioventricular block and pericardial effusion following transseptal puncture, which was treated by pericardiocentesis. All dogs recovered uneventfully. Fluoroscopy time was limited to a median of 7 min (0–45 min) and almost exclusively associated with transseptal puncture. Three-dimensional EAM of all cardiac chambers, including mapping-guided biopsy and transseptal puncture is feasible in small dogs. Complications are similar to those reported in human patients. This suggests a potential added value of 3D EAM to conventional electrophysiology in dogs with arrhythmias. [ABSTRACT FROM AUTHOR]

Background There is a growing interest in health care of elderly dogs; however, scientific information about physical and laboratory examination findings in this age group is limited. Objectives To describe systolic blood pressure ( SBP), and results of physical examination and laboratory tests in senior and geriatric dogs that were judged by the owner to be healthy. Animals Hundred client-owned dogs. Methods Dogs were prospectively recruited. Owners completed a questionnaire. SBP measurement, physical, orthopedic and neurologic examination, direct fundoscopy and Schirmer tear test were performed. Complete blood count, serum biochemistry, and urinalysis were evaluated. Results Forty-one senior and 59 geriatric dogs were included. Mean SBP was 170 ± 38 mmHg, and 53 dogs had SBP > 160 mmHg. Thirty-nine animals were overweight. A heart murmur was detected in 22, severe calculus in 21 and 1 or more (sub)cutaneous masses in 56 dogs. Thirty-two dogs had increased serum creatinine, 29 hypophosphatemia, 27 increased ALP, 25 increased ALT, and 23 leukopenia. Crystalluria, mostly amorphous crystals, was commonly detected (62/96). Overt proteinuria and borderline proteinuria were detected in 13 and 18 of 97 dogs, respectively. Four dogs had a positive urine bacterial culture. Frequency of orthopedic problems, frequency of (sub)cutaneous masses, and platelet count were significantly higher in geriatric compared with senior dogs. Body temperature, hematocrit, serum albumin, and serum total thyroxine concentration were significantly lower in geriatric compared with senior dogs. Conclusions and Clinical Importance Physical and laboratory abnormalities are common in apparently healthy elderly dogs. Veterinarians play a key role in implementing health screening and improving health care for elderly pets. [ABSTRACT FROM AUTHOR]

With the recent development of whole-exome sequencing enrichment designs for the dog, a novel tool for disease-association studies became available. The aim of disease-association studies is to identify one or a very limited number of putative causal variants or genes from the large pool of genetic variation. To maximize the efficiency of these studies and to provide some directions of what to expect, we evaluated the effect on variant reduction for various combinations of cases and controls for both dominant and recessive types of inheritance assuming variable degrees of penetrance and detectance. In this study, variant data of 14 dogs (13 Labrador Retrievers and one Dogue de Bordeaux), obtained by whole-exome sequencing, were analyzed. In the filtering process, we found that unrelated dogs from the same breed share up to 70% of their variants, which is likely a consequence of the breeding history of the dog. For the designs tested with unrelated dogs, combining two cases and two controls gave the best result. These results were improved further by adding closely related dogs. Reduced penetrance and/or detectance has a drastic effect on the efficiency and is likely to have a profound effect on the sample size needed to elucidate the causal variant. Overall, we demonstrated that sequencing a small number of dogs results in a marked reduction of variants that are likely sufficient to pinpoint causal variants or genes. [ABSTRACT FROM AUTHOR]

Background Sighthound breeds are known to have different cardiac sizes and dimensions from other breeds; therefore, breed-specific references are required to avoid misinterpretation of echocardiographic findings. End-diastolic volume (EDV) and end-systolic volume (ESV) reference intervals derived from Simpson's method of discs (SMOD) do not exist for Salukis or Whippets. Objectives To establish EDV and ESV reference intervals for SMOD in Salukis and Whippets. Animals 110 Salukis and 119 Whippets. Methods Reference intervals for SMOD with and without normalization to body surface area (BSA) were established using the right parasternal and left apical views in 93 healthy Salukis and 82 healthy Whippets. Volumes were compared between both echocardiographic views, genders, and racing and show pedigree dogs. The 90% reference intervals were calculated using the robust method. Results Agreement between right-sided and left-sided echocardiographic views was good. Reference intervals indexed to body surface area (BSA) for Whippets were 59–109 mL/m² for end-diastolic volume index and 18–53 mL/m² for end-systolic volume index. Corresponding values for Salukis were 68–126 mL/m² for end-diastolic volume index and 27–64 mL/m² for end-systolic volume index. There were no indexed volume differences between male and female or racing and show pedigree dogs in both breeds. The non-normalized volumes significantly differed between genders. Conclusions and clinical importance Whippets and Salukis had larger systolic and diastolic left ventricular volumes compared with other breeds. This study provided echocardiographic reference intervals for SMOD-derived left ventricular volumes for these athletic breeds. [ABSTRACT FROM AUTHOR]

Background: Blood urea nitrogen and serum creatinine concentrations only detect a decrease of >75% of renal functional mass. Therefore, there is a need for markers that allow early detection and localization of renal damage. Hypothesis: Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein (uRBP), and N-acetyl-β-d-glucosaminidase (uNAG) concentrations are increased in dogs with chronic kidney disease (CKD) compared with healthy controls and in healthy older dogs compared with young dogs. Animals: Ten dogs with CKD, 10 healthy young dogs (age 1–3 years), and 10 healthy older dogs (age > 7 years) without clinically relevant abnormalities on physical examination, hematology, biochemistry, and urinalysis. Methods: Urinary markers were determined using an ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test were used to compare the different groups of dogs. Results: uALB/c, uRBP/c, and uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant difference was found for uCRP, which was not detectable in the healthy dogs and only in 3 of the CKD dogs. Between the healthy young and older dogs, no significant difference was detected for any of the markers. Conclusion: The urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs with CKD compared with healthy controls. Additional studies are needed to evaluate the ability of these markers to detect renal disease before the onset of azotemia. [ABSTRACT FROM AUTHOR]

Background: Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking. Hypothesis: Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism. Animals: Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis. Methods: Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n = 14) and at 1 month (T1, n = 14) and at 6 months (T6, n = 11) after beginning levothyroxine supplementation therapy (20 μg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean ± standard deviation. Results: At T0, the average age of dogs in the study group was 6.3 ± 1.4 years. Their average body weight decreased from 35 ± 18 kg at T0 to 27 ± 14 kg at T6 ( P < .05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6 ± 0.4 mL/min/kg at T0, 2.1 ± 0.4 at T1, and 2.0 ± 0.4 at T6 ( P < .01). Conclusion: GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly. [ABSTRACT FROM AUTHOR]

Renal dysfunction in dogs envenomed by poisonous snakes is currently detected using traditional serum and urinary biomarkers such as creatinine and proteinuria. However, these markers lack sensitivity at the early stages of renal dysfunction and their diagnostic accuracy is affected by pre-analytical factors commonly occurring in these dogs, such as haemolysis and haemoglobinuria. Early detection of renal dysfunction would allow for the identification of dogs requiring intensive treatment and monitoring and may help inform prognosis. The aim of this study was to evaluate the performance of several novel urinary biomarkers of glomerular dysfunction, namely, urinary albumin (uAlb), immunoglobulin G (ulgG) and C-reactive protein (uCRP) and of proximal tubular dysfunction (urinary retinol binding protein (uRBP)) compared to traditional end points in dogs with renal damage caused by snake envenomation. Biomarker results were compared between 19 dogs bitten by snakes producing either neurotoxins or cytotoxins and 10 clinically healthy controls. uAlb, ulgG, and uRBP were significantly increased in snake-envenomed dogs at presentation compared to controls, whereas only ulgG and uCRP were significantly elevated 24 h post-envenomation. The urinary proteinxreatinine ratio was also increased in envenomed dogs compared to controls, but because of the presence of haematuria and haemoglobinuria, differentiation between pre-renal and renal proteinuria was not possible. The results showed that these novel urinary biomarkers may assist in better detecting renal dysfunction in dogs envenomed by poisonous snakes at the acute disease stage compared to traditional laboratory endpoints. [ABSTRACT FROM AUTHOR]