Utility of focused cardiac ultrasonography training in veterinary students to differentiate stages of subclinical myxomatous mitral valve disease in dogs.

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.

Development of an Informatics Algorithm to Link Seasonal Infectious Diseases to Birth-Dependent Diseases Across Species: A Case Study with Osteosarcoma.

Many diseases have been linked with birth seasonality, and these fall into four main categories: mental, cardiovascular, respiratory and women's reproductive health conditions. Informatics methods are needed to uncover seasonally varying infectious diseases that may be responsible for the increased birth month-dependent disease risk observed. We have developed a method to link seasonal infectious disease data from the USA to birth month dependent disease data from humans and canines. We also include seasonal air pollution and climate data to determine the seasonal factors most likely involved in the response. We test our method with osteosarcoma, a rare bone cancer. We found the Lyme disease incidence was the most strongly correlated significant factor in explaining the birth month-osteosarcoma disease pattern (R=0.418, p=2.80X10-23), and this was true across all populations observed: canines, pediatric, and adult populations.

Applied Veterinary Informatics: Development of a Semantic and Domain-Specific Method to Construct a Canine Data Repository.

Animals are used to study the pathogenesis of various human diseases, but typically as animal models with induced disease. However, companion animals develop disease spontaneously in a way that mirrors disease development in humans. The purpose of this study is to develop a semantic and domain-specific method to enable construction of a data repository from a veterinary hospital that would be useful for future studies. We developed a two-phase method that combines semantic and domain-specific approaches to construct a canine data repository of clinical data collected during routine care at the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania (PennVet). Our framework consists of two phases: (1) a semantic data-cleaning phase and (2) a domain-specific data-cleaning phase. We validated our data repository using a gold standard of known breed predispositions for certain diseases (i.e., mitral valve disease, atrial fibrillation and osteosarcoma). Our two-phase method allowed us to maximize data retention (99.8% of data retained), while ensuring the quality of our result. Our final population contained 84,405 dogs treated between 2000 and 2017 from 194 distinct dog breeds. We observed the expected breed associations with mitral valve disease, atrial fibrillation, and osteosarcoma (P < 0.05) after adjusting for multiple comparisons. Precision ranged from 60.0 to 83.3 for the three diseases (avg. 74.2) and recall ranged from 31.6 to 83.3 (avg. 53.3). Our study describes a two-phase method to construct a clinical data repository using canine data obtained during routine clinical care at a veterinary hospital.

Cytological diagnosis of cardiac masses with ultrasound guided fine needle aspirates.

BACKGROUND: Cardiac masses are uncommon in the canine population. When present, an attempt should be made to obtain a definitive diagnosis. Our goal with this case series was to report that as long as anatomic location permits, obtaining fine needle aspirates (FNAs) for cytological evaluation is practical, safe, and may provide a definitive diagnosis. METHODS: Our database has been retrospectively searched for cases where FNA of cardiac masses have been performed. RESULTS: A total of six cases were retrieved. Four dogs were under general anaesthesia and two were sedated. Ultrasound guided transthoracic FNAs were obtained in all cases with only minor complications: mild self-limiting pericardial effusion (n = 1) and one ventricular ectopic complex (n = 1). All dogs were closely monitored during the procedure (pulse oximetry, electrocardiography and blood pressure). A diagnosis was obtained in all cases: inflammation (n = 1), haemangiosarcoma (n = 2), sarcoma (n = 2) and chemodectoma (n = 1). CONCLUSION: A cytological diagnosis allows clinicians to make appropriate clinical decisions, has dramatic impact on treatment recommendations and gives information about prognosis.

Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance.

Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D. immitis and identified genetic markers that are correlated with, and therefore can predict ML resistance. ML controlled studies showed that LOE strains of D. immitis established infections in dogs despite chemoprophylaxis with oral ivermectin or injectable moxidectin. A whole genome approach was used to search for loci associated with the resistance phenotype. Many loci showed highly significant differences between pools of susceptible and LOE D. immitis. Based on 186 potential marker loci, Sequenom(®) SNP frequency analyses were conducted on 663 individual parasites (adult worms and microfilariae) which were phenotypically characterized as susceptible (SUS), confirmed ML treatment survivors/resistant (RES), or suspected resistant/loss of efficacy (LOE) parasites. There was a subset of SNP loci which appears to be promising markers for predicting ML resistance, including SNPs in some genes that have been associated with ML resistance in other parasites. These data provide unequivocal proof of ML resistance in D. immitis and identify genetic markers that could be used to monitor for ML resistance in heartworms.

Evaluation of L-lactate and cardiac troponin I in horses undergoing emergency abdominal surgery.

OBJECTIVE: To evaluate changes in plasma cardiac troponin I (cTnI) and L-lactate (LLt) as prognostic indicators in horses undergoing emergency abdominal surgery. DESIGN: Prospective observational study. SETTING: Veterinary teaching hospital. ANIMALS: Thirty-four horses undergoing emergency abdominal surgery. INTERVENTIONS: Serial blood sampling during various times during hospitalization (hospital admission, and 12, 24, 48, and 72 h postoperatively) evaluating cTnI and LLt concentrations. MEASUREMENTS AND MAIN RESULTS: All horses required surgery for correction of a strangulating (n = 29) or nonstrangulating obstruction (n = 5) of the small or large intestine. Twenty-seven horses survived to discharge; 7 were euthanized either during (n = 1) or after (n = 6) surgery due to disease severity or systemic complications associated with the primary gastrointestinal lesion. Preoperative cTnI concentrations were increased above the normal reference interval in 24% of horses (8/34, median = 0.01 ng/mL, range = 0-12.23 ng/mL), whereas LLt concentrations were increased above the normal reference interval in 88% of horses (30/34, median = 3.37 mmol/L, range = 0.77-13.26 mmol/L). The LLt concentration was significantly higher (P < 0.05) in nonsurviving compared with surviving horses at admission, and at 24 and 72 hours postoperatively. No significant difference in the cTnI concentration was detected between groups at admission. However, the cTnI concentration was significantly higher (P<0.05) in nonsurviving compared with surviving horses at all time points postoperatively. CONCLUSIONS: Measurement of both LLt and cTnI concentrations may provide information for prognostication in surgical colic horses. Marked increases in admission concentrations of LLt (median 7.56 mmol/L) and even moderate postoperative increases in cTnI concentration (median 0.97 ng/mL) may both indicate a poor prognosis in critically ill horses following abdominal surgery.

Biochemical variables in free-ranging white-tailed deer (Odocoileus virginianus) after chemical immobilization in clover traps or via ground-darting.

The objective of this prospective observational cohort study in free-ranging female white-tailed deer (Odocoileus virginianus) was to compare the physiologic effects of two methods of anesthetic drug administration: hand-injection in Clover traps and remote injection by dart after ground-stalking. Six trapped and 14 darted female deer were injected with a median (minimum, maximum) of 590 microg/kg butorphanol (401, 1070 microg/kg), plus 235 microg/kg medetomidine (160, 429 microg/kg) intramuscularly. In the trap, the deer struggled when approached and were restrained for injection. Darted deer sprinted away after injection. Once immobilized, deer were transported to a veterinary hospital where blood was collected and vital signs were measured on admission. Admission data from a subset of deer in which measurements were taken within 40 min of trapping (n = 6) or darting (n = 5) were analyzed. After salpingectomy under isoflurane and while still anesthetized, another blood sample was collected from all 20 deer. Body weight and immobilization drug doses were not different between groups. On admission, most deer from both groups were hypoxemic, although the darted deer were significantly more hypoxemic. The median rectal temperature in trapped deer was higher than in darted deer, and temperatures higher than 39 degrees C only occurred in trapped deer. The median heart rate in trapped deer was more than twice that in darted deer. Trapped deer had lower median pH and base excess; in trapped deer, the median plasma lactate concentration was more than fivefold higher than in darted deer. After surgery, the median serum creatine kinase concentration was nearly 10-fold higher in trapped deer, and the median cardiac troponin I concentration was higher in trapped deer but undetectable in 10 of 14 darted deer. The white-tailed deer immobilized by hand-injection in Clover traps experienced more severe physiologic perturbations than deer remotely injected by dart after ground-stalking. These perturbations might be sufficient to cause myocardial damage.

Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that plays an important role in integrin-mediated signal transduction. To explore the role and mechanisms of FAK in cardiac development, we inactivated FAK in embryonic cardiomyocytes by crossing the floxed FAK mice with myosin light chain-2a (MLC2a) Cre mice, which expressed Cre as early as embryonic day 9.5 in the heart. The majority of conditional FAK knockout mice generated from MLC2a-Cre (CFKO-2a) died in the embryonic stage with thin ventricular wall and ventricular septal defects. A small fraction of CFKO-2a mice survived to adulthood with spontaneous eccentric right ventricle hypertrophy. Transmission electron microscopy analysis displayed swelling in the rough endoplasmic reticulum in CFKO-2a embryonic cardiomyocytes. We found that decreased cell proliferation, but not increased cell apoptosis or differentiation, is the reason for the thin ventricular wall in CFKO-2a mice. Microarray analysis suggests that myocyte enhancer factor 2a (MEF2a) can be regulated by FAK and that inactivation of FAK in the embryonic heart compromised MEF2a expression. Last, we found that Src, but not PI3K, is important in mediating signal transduction for the regulation of MEF2a by FAK. Together, these results identified the role and mechanisms of FAK in embryonic cardiac development.

Molecular composition of the intercalated disc in a spontaneous canine animal model of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by ventricular arrhythmias, sudden death, and fatty or fibrofatty replacement of right ventricular myocytes. Recent studies have noted an association between human ARVD/C and molecular remodeling of intercalated disc structures. However, progress has been constrained by limitations inherent to human studies. OBJECTIVE: We studied the molecular composition of the intercalated disc structure in a naturally occurring animal model of ARVD/C (Boxer dogs). METHODS: We studied hearts from 12 Boxers with confirmed ARVD/C and 2 controls. Ventricular sections from 4 animals were examined by immunofluorescent microscopy. Frozen tissue samples were used for Western blot analysis. Proteins investigated were N-cadherin, plakophilin 2, desmoplakin, plakoglobin, desmin, and connexin 43 (Cx43). RESULTS: In control dogs, all proteins tested by immunofluorescence analysis yielded intense localized signals at sites of end-to-end cell apposition. In contrast, myocardial tissues from ARVD/C-afflicted Boxers showed preservation of N-cadherin staining but loss of detectable signal for Cx43 at the intercalated disc location. Western blots indicated that the Cx43 protein was still present in the samples. Gene sequencing analysis showed no mutations in desmoplakin, plakoglobin, Cx43, or plakophilin 2. CONCLUSION: Mutation(s) responsible for ARVD/C in Boxers lead, directly or indirectly, to severe modifications of mechanical and electrical cell-cell interactions. Furthermore, significant reduction in gap junction formation may promote a substrate for malignant ventricular arrhythmias. This model may help to advance our understanding of the molecular basis, pathophysiology, and potential therapeutic approach to patients with ARVD/C.

Marked pleural effusion causing right atrial collapse simulating cardiac tamponade in a dog.

A 16-month-old, female German shepherd dog was presented with severe bicavitary effusions. A diaphragmatic hernia was diagnosed by thoracic radiography. An echocardiogram performed prior to surgical repair of the hernia revealed signs of cardiac tamponade, with right atrial collapse, in the absence of pericardial effusion. Right atrial collapse was presumed to be secondary to severe pleural effusion. At surgery, no pericardial disease was identified. Surgical correction of the diaphragmatic hernia resulted in resolution of the pleural and peritoneal effusions. Follow-up echocardiography demonstrated resolution of the signs of cardiac tamponade.

Thoracoscopic pericardiotomy as a palliative treatment in a cow with pericardial lymphoma.

A 5-year-old Holstein cow, pregnant with a valuable calf, was presented with signs of heart failure (tachycardia, peripheral edema, and distended jugular veins) related to pericardial lymphoma and associated cardiac tamponade. In addition, pleural effusion was present in both hemithoraces. Medical treatment, which consisted of repeated pericardiocenteses, placement of indwelling pleural catheters, administration of intravenous fluid therapy, antibiotics and anti-inflammatory drugs, was ineffective in controlling recurrence of clinical signs despite a temporary improvement. A standing thoracoscopic pericardiotomy was performed in an attempt to reduce clinical signs of heart failure and to prolong life. Clinical signs of heart failure abated and no recurrence was seen. Standing thoracoscopic pericardiotomy along with possible corticosteroids can be recommended as palliative treatment in an effort to extend life for reproductive performance in genetically valuable animals.

Use of transesophageal echocardiography for visualization of the patent ductus arteriosus during transcatheter coil embolization.

Transesophageal echocardiography (TEE) enhances our ability to see the patent ductus arteriosus in the dog. The improved visualization may potentially improve our ability to perform transcatheter coil embolization in patients that are more likely to have a successful outcome. This report uses still and video images to detail the specifics of coil embolization as performed with the assistance of TEE and compares the images with those of angiography, surgery and postmortem examination.