Validation and preliminary data from a health-related quality of life questionnaire for owners of dogs with cardiac disease.

BACKGROUND: Cardiac disease in dogs impacts the quality of life (QoL) of their owners, but owners' QoL has not been comprehensively assessed in this population. OBJECTIVES: To develop, validate, and provide preliminary data from a health-related QoL (hrQoL) questionnaire for owners of dogs with cardiac disease. SUBJECTS: A total of 141 owners of dogs with cardiac disease were studied. METHODS: An owner hrQoL (O-hrQoL) questionnaire containing 20 items related to areas of a person's life that could be impacted by caring for a dog with cardiac disease was developed and administered to owners of dogs with cardiac disease. The highest possible total score was 100, with higher scores indicating a worse hrQoL. Readability, internal consistency, face and construct validity, and item-total correlations were assessed. RESULTS: Median O-hrQoL score was 35 (range, 0-87). The questionnaire had good internal consistency (Cronbach's α = 0.933), construct validity (Spearman's r = 0.38-0.53; Kendall's τ = 0.30-0.43; P < .001), and item-total correlation (Spearman's r = 0.44-0.79; Kendall's τ = 0.34-0.66; all P < .001). Fifty percent of owners indicated a negative effect of dogs' cardiac disease on their own QoL, but all owners responded that caring for their dogs either had strengthened (n = 76; 53.9%) or had no effect on their relationship with their dog (n = 65; 46.1%). CONCLUSIONS AND CLINICAL IMPORTANCE: The O-hrQoL questionnaire had good validity, and results suggest that owners' QoL is significantly impacted by caring for dogs with cardiac disease. Additional research on effective approaches to minimizing the negative effects of a dog's cardiac disease on the owner is warranted.

Extracellular vesicular microRNAs as potential biomarker for early detection of doxorubicin-induced cardiotoxicity.

BACKGROUND: Long-term use of doxorubicin (DOX) is limited by cumulative dose-dependent cardiotoxicity. OBJECTIVES: Identify plasma extracellular vesicle (EV)-associated microRNAs (miRNAs) as a biomarker for cardiotoxicity in dogs by correlating changes with cardiac troponin I (cTnI) concentrations and, echocardiographic and histologic findings. ANIMALS: Prospective study of 9 client-owned dogs diagnosed with sarcoma and receiving DOX single-agent chemotherapy (total of 5 DOX treatments). Dogs with clinically relevant metastatic disease, preexisting heart disease, or breeds predisposed to cardiomyopathy were excluded. METHODS: Serum concentration of cTnI was monitored before each treatment and 1 month after the treatment completion. Echocardiography was performed before treatments 1, 3, 5, and 1 month after completion. The EV-miRNA was isolated and sequenced before treatments 1 and 3, and 1 month after completion. RESULTS: Linear mixed model analysis for repeated measurements was used to evaluate the effect of DOX. The miR-107 (P = .03) and miR-146a (P = .02) were significantly downregulated whereas miR-502 (P = .02) was upregulated. Changes in miR-502 were significant before administration of the third chemotherapeutic dose. When stratifying miRNA expression for change in left ventricular ejection fraction, upregulation of miR-181d was noted (P = .01). Serum concentration of cTnI changed significantly but only 1 month after treatment completion, and concentrations correlated with left ventricular ejection fraction and left ventricular internal dimension in diastole. CONCLUSION AND CLINICAL SIGNIFICANCE: Downregulation of miR-502 was detected before significant changes in cTnI concentrations or echocardiographic parameters. Further validation using a larger sample size will be required.

Pilot study of a myostatin antagonist in dogs with cardiac cachexia.

OBJECTIVES: Cardiac cachexia, a loss of lean body mass caused by heart disease, often accompanies congestive heart failure (CHF). Blocking myostatin, which is a protein that inhibits muscle growth, appears to greatly enhance muscle size and strength in rodent models and human clinical trials. The objective of this study was to evaluate a dog-specific myostatin antagonist (CAP-031) in a pilot study to test its safety and efficacy in dogs with CHF and cardiac cachexia. ANIMALS: Dogs with CHF and cardiac cachexia. METHODS: Eligible dogs received four weekly subcutaneous injections of CAP-031. Endpoints were body weight, body condition score (BCS, on a 1-9 scale), muscle condition score (MCS, on a five-point scale, where 0 = no muscle loss and 4 = severe muscle loss), appetite, and a quality of life (QOL) score. RESULTS: Seven dogs with CHF and moderate-to-severe cachexia were enrolled in the study. For the six dogs that completed the study, the median age was 8.8 years (range 6.4-10.6). At baseline, the median body weight was 27.0 kg (range 17.3-62.0), the median BCS was 4 (2-5), and median MCS was 3 (3-4). There were no significant changes in body weight, BCS, appetite, or QOL score. The change in MCS (from a median of 3 at baseline to a median of 2.5 at week 4) was not statistically significant (p = 0.06). CONCLUSIONS: The myostatin antagonist appeared to be well tolerated in most dogs. Earlier identification of cachexia is important, and randomized, controlled trials of myostatin antagonists or other drugs to treat cardiac cachexia are needed.

Long-term outcome of physiologic VDD pacing versus non-physiologic VVI pacing in dogs with high-grade atrioventricular block.

OBJECTIVE: To compare the long-term outcome associated with physiologic VDD and non-physiologic VVI or VVIR pacing in dogs with high-grade atrioventricular block. ANIMALS: Forty-nine paced dogs with high-grade atrioventricular block were included. METHODS: Retrospective review of medical records, thoracic radiographs and echocardiograms for all dogs. Patient owners and referring veterinarians were contacted for survival times and a satisfaction questionnaire was submitted to the owners. Survival times, complication rates, resolution of clinical signs, and owner satisfaction were compared between the pacing modalities. RESULTS: A single lead VDD pacemaker was implanted in 19 dogs (39%) whereas 30 dogs (61%) were treated with VVI pacing. The median survival time for all dogs post-pacemaker implantation was 24.5 months. Survival time was significantly decreased in dogs that were older at the time of presentation or that presented with ventricular tachycardia or reduced left ventricular fractional shortening. Median survival times after implantation were not significantly different between pacing modalities (P = 0.29). Major complication rates were 11% within the VDD group and 20% within the VVI group and were not significantly different (P = 0.46). Minor complications were significantly higher within the VDD group than within the VVI group (47% versus 7% respectively; P < 0.01) due to a higher number of dogs in the VDD group experiencing transient ventricular premature contractions in the immediate post-implantation time period. Resolution of clinical signs, owner satisfaction, and quality of life perception were considered excellent in both groups. CONCLUSIONS: No long-term clinical benefit of VDD over VVI pacing could be identified in the present study.

Assessment of the responsiveness of the Cats' Assessment Tool for Cardiac Health (CATCH) Questionnaire.

OBJECTIVES: To evaluate the responsiveness and optimal timing of a validated health-related quality of life questionnaire, and to assess the relationship between quality of life, severity of disease, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cats with acute congestive heart failure (CHF). ANIMALS: Thirty client-owned cats with acute CHF. METHODS: Echocardiography, International Small Animal Cardiac Health Council (ISACHC) stage, and NT-proBNP were assessed in cats within 36 h of admission. The Cats' Assessment Tool for Cardiac Health (CATCH) Questionnaire (range of 0-80, with 80 being the worst possible score) was completed by cat owners and ISACHC stage was assessed at the time of hospital discharge, 3 days after discharge, and 7-14 days after discharge. NT-proBNP concentration was reassessed 7-14 days after discharge. RESULTS: The ISACHC stage at time of admission improved significantly by reevaluation 7-14 days after discharge (P < 0.001). The decrease in median NT-proBNP concentration from time of admission (655 pmol/L; range, 188 to >1500 pmol/L) to reevaluation (583 pmol/L; range, 41 to >1500 pmol/L) was not significant (P = 0.59). Median CATCH score was 26 (range, 0-70) at baseline, 19 (range, 0 to 61) at discharge, and 19 (range, 2-49) 7-14 days after discharge (P = 0.89). CATCH scores did not correlate with NT-proBNP concentrations or ISACHC stage. CONCLUSIONS: These results suggest that the CATCH questionnaire requires further refinement for uses requiring a responsive instrument in cats with acute CHF.

Validation of a commercially available enzyme immunoassay for measurement of plasma antidiuretic hormone concentration in healthy dogs and assessment of plasma antidiuretic hormone concentration in dogs with congestive heart failure.

OBJECTIVE: To validate the use of a human enzyme immunoassay (EIA) kit for measurement of plasma antidiuretic hormone (ADH) concentration in dogs and evaluate plasma ADH concentrations in dogs with congestive heart failure (CHF) attributable to acquired cardiac disease, compared with findings in healthy dogs. ANIMALS: 6 healthy dogs and 12 dogs with CHF as a result of chronic degenerative valve disease or dilated cardiomyopathy. PROCEDURES: Plasma samples from the 6 healthy dogs were pooled and used to validate the EIA kit for measurement of plasma ADH concentration in dogs by assessing intra-assay precision, dilutional linearity, and spiking recovery. Following validation, plasma ADH concentrations were measured in the 6 healthy dogs and in the 12 dogs with CHF for comparison. RESULTS: The EIA kit measured ADH concentrations in canine plasma samples with acceptable intra-assay precision, dilutional linearity, and spiking recovery. The intra-assay coefficient of variation was 11%. By use of this assay, the median plasma concentration of ADH in dogs with CHF was 6.15 pg/mL (SD, 3.2 pg/mL; range, 4.18 to 15.47 pg/mL), which was significantly higher than the median concentration in healthy dogs (3.67 pg/mL [SD, 0.93 pg/mL; range, 3.49 to 5.45 pg/mL]). CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentrations in dogs can be measured with the tested EIA kit. Plasma ADH concentrations were higher in dogs with CHF induced by acquired cardiac disease than in healthy dogs. This observation provides a basis for future studies evaluating circulating ADH concentrations in dogs with developing heart failure.

Evaluation of a training course in focused echocardiography for noncardiology house officers.

OBJECTIVE: To determine whether a training course in focused echocardiography can improve the proficiency of noncardiology house officers in accurately interpreting cardiovascular disease and echocardiography findings in dogs entering the emergency room setting. DESIGN: Prospective, blinded, educational study. SETTING: University veterinary teaching hospital. STUDY SUBJECTS: House officers underwent training in focused echocardiography. Fifteen dogs, including normal dogs and dogs with stable congenital or acquired cardiac disease, were used as study subjects during the laboratory session. INTERVENTIONS: A 6-hour curriculum on focused echocardiography was developed that included didactic lectures, clinical cases, and hands-on echocardiography. MEASUREMENTS AND MAIN RESULTS: Pre- and postcourse written examinations were administered to participants. House officers attended didactic lectures that were subsequently followed by a hands-on laboratory session and practical examination, which involved performing transthoracic echocardiography on dogs with and without cardiovascular disease. Twenty-one house officers completed the focused echocardiography training course. Written examination scores were 57 ± 12% before and 75 ± 10% after training (P < 0.001). Following the course, 97% of participants in the practical examination were able to obtain the correct right parasternal short- or long-axis view. Posttraining, most participants correctly identified pleural effusion (90%) and pericardial effusion (95%) and discriminated normal atrial size from atrial enlargement (86%). However, successful identification of a cardiac mass, volume status, and ability to recognize a poor quality study as nondiagnostic remained relatively low. Most trainees responded that the length of hands-on laboratory training was too abbreviated and that the course should be > 6 hours. CONCLUSION: A focused echocardiography training course improved knowledge and yielded acceptable proficiency in some echocardiographic findings commonly identified in the emergency room. This training course was not able to provide the skills needed for house officers to accurately assess fluid volume status, identify cardiac masses, ventricular enlargement or hypertrophy, and certain cardiac diseases.

Body size and metabolic differences in Maine Coon cats with and without hypertrophic cardiomyopathy.

An interplay between growth, glucose regulation and hypertrophic cardiomyopathy (HCM) may exist, but has not been studied in detail. The purpose of this study was to characterize morphometric features, insulin-like growth factor-1 (IGF-1) and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition score (BCS), head length and width, and abdominal circumference were measured in Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for measurement of humerus length, and fourth and twelfth vertebrae length) were also performed. Blood was collected for biochemistry profile, DNA testing, insulin and IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and MYBPC-, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and MYBPC-, n = 30). There were no significant differences in any measured parameter between MYBPC+ and MYBPC- cats. Cats with HCM were significantly older (P <0.001), heavier (P = 0.006), more obese (P = 0.008), and had longer humeri (P = 0.02) compared with the HCM- group. Cats with HCM also had higher serum glucose (P = 0.01), homeostasis model assessment (HOMA) and IGF-1 (P = 0.01) concentrations, were from smaller litters (P = 0.04), and were larger at 6 months (P = 0.02) and at 1 year of age (P = 0.03). Multivariate analysis revealed that age (P <0.001), BCS (P = 0.03) and HOMA (P = 0.047) remained significantly associated with HCM. These results support the hypothesis that early growth and nutrition, larger body size and obesity may be environmental modifiers of genetic predisposition to HCM. Further studies are warranted to evaluate the effects of early nutrition on the phenotypic expression of HCM.

Auscultatory, echocardiographic, biochemical, nutritional, and environmental characteristics of mitral valve disease in Norfolk terriers.

OBJECTIVES: In order to more fully understand degenerative mitral valve disease (DMVD) in the Norfolk terrier, we sought to characterize findings from the physical and echocardiographic examination; biochemical, biomarker, and nutritional profiles; and select environmental variables from a cohort of apparently healthy Norfolk terriers. ANIMALS, MATERIALS AND METHODS: Overtly healthy Norfolk terriers ≥ 6 yrs old were recruited by 3 different veterinary hospitals and underwent historical, physical, electrocardiographic (ECG), and 2D/color-flow Doppler echocardiographic examinations. Anterior mitral valve leaflet length, maximal thickness, area, and degree of prolapse were measured or calculated from two-dimensional images. Blood samples were obtained for serum biochemistry, serum serotonin, plasma NT-proBNP, amino acid profile, C-reactive protein, and cardiac troponin I. RESULTS: Of the 48 dogs entered into the study, 23 (48%) had murmurs, 2 (4%) had mid-systolic clicks, 11 (23%) had ECG P pulmonale, and 41 (85%) were deemed to have echocardiographic evidence of DMVD, including 18 Norfolk terriers without a murmur. Seven (15%), 28 (58%), and 13 (27%) dogs were classified as normal (stage 0), International Small Animal Cardiac Health Council (ISACHC) stage 1a, and 1b, respectively. Mean indexed echocardiographic mitral leaflet thickness (P = 0.017), area (P = 0.0002), prolapse (P = 0.0004), and left atrial to aortic diameter (P = 0.01) were significantly different between ISACHC 0, 1a, and 1b. CONCLUSION: DMVD is relatively common in Norfolk terriers and echocardiographic changes consistent with mild DMVD can be seen in dogs without a heart murmur.

Cardiovascular dysfunction in sepsis and critical illness.

Myocardial dysfunction is commonly encountered in humans, and presumably in dogs with sepsis and critical illness. This dysfunction contributes to increased mortality. With management of the underlying diseases and an understanding of the processes contributing to myocardial dysfunction, steps may be taken to mitigate the consequences of cardiac impairment. Clinical findings, proposed pathophysiologic mechanisms, and current treatment considerations are discussed. Further study is needed to find practical ways to identify myocardial dysfunction and to determine whether timed interventions intended to augment cardiac performance will reduce mortality in this patient population.

Anomalous left-to-right shunting communication between the ascending aorta and right pulmonary artery in a dog.

Anomalies of conotruncal septation are rare in dogs and uncommon in humans. Congenital conotruncal defects most commonly reported in veterinary medicine include aorto-pulmonary window and persistent truncus arteriosus. We report a case of an anomalous vessel connecting the ascending aorta to the right pulmonary artery causing left-to-right shunting, left-sided volume overload, and pulmonary overcirculation. Transesophageal echocardiography, cardiac catheterization, and contrast-enhanced computed tomography assisted in the diagnosis and facilitated the surgical correction of the anomalous vessel. The authors hypothesize this defect represents an unusual anomalous vessel connecting the ascending aorta to the right pulmonary artery.

Aortic dissection associated with an obstructive aortic chondrosarcoma in a dog.

A 6-year-old, 35-kg, female spayed German wirehaired pointer was referred for evaluation of collapse/seizure-like activity and a suspected mediastinal mass. Echocardiographic examination revealed an obstructive, intraluminal aortic mass with aortic dissection. Gross and histopathological findings confirmed the aortic dissection with right pulmonary artery compression and an aortopulmonary fistula. The mass was histologically consistent with an intraluminal chondrosarcoma. To the authors knowledge this case represents only the second case of aortic chondrosarcoma in a dog, and interestingly the first case in either a dog or human to have aortic dissection associated with aortic obstruction by an intraluminal aortic tumor.

Echocardiographic evaluation of dogs with dysautonomia.

OBJECTIVE: To describe echocardiographic findings in dogs with dysautonomia. DESIGN: Prospective case series: ANIMALS: 20 dogs with dysautonomia (13 confirmed during necropsy and 7 with results of antemortem testing [tear production, pilocarpine response test, atropine response test, and ID histamine response] supportive of the diagnosis). PROCEDURES: Dogs with dysautonomia were evaluated by use of echocardiography, and M-mode measurements were obtained on all dogs. A dobutamine response test was performed on 1 dog, starting at a rate of 1 microg/kg/min and doubling the rate every 15 minutes until fractional shortening (FS) increased to > 2 times the baseline value. RESULTS: Evidence of systolic dysfunction was detected in 17 of 20 dogs with dysautonomia, as determined on the basis of FS (median, 17.9%; range, 4.0% to 31.1%). Left ventricular internal dimension during diastole or left ventricular internal dimension during systole was enlarged in 4 of 20 and 14 of 20 dogs, respectively. Enlargement of the left atrium or aorta was identified in 3 of 15 and 1 of 15 dogs in which it was measured, respectively. Administration of dobutamine at a rate of 4 microg/kg/min resulted in dramatic improvement in FS (increase from 4% to 17%) in the 1 dog tested. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that echocardiographic evidence of diminished systolic function was common in dogs with dysautonomia. Whether the diminished function was a result of sympathetic denervation or myocardial hibernation was unclear, although myocardial hibernation was more likely.

Assessment of serum N-terminal pro-B-type natriuretic peptide concentration for differentiation of congestive heart failure from primary respiratory tract disease as the cause of respiratory signs in dogs.

OBJECTIVE: To determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is useful in discriminating between cardiac and noncardiac (ie, primary respiratory tract disease) causes of respiratory signs (ie, coughing, stertor, stridor, excessive panting, increased respiratory effort, tachypnea, or overt respiratory distress) in dogs. DESIGN: Multicenter cross-sectional study. ANIMALS: P 115 dogs with respiratory signs. PROCEDURES: Dogs with respiratory signs were solicited for study. Physical examination, thoracic radiography, and echocardiography were used to determine whether respiratory signs were the result of cardiac (ie, congestive heart failure) or noncardiac (ie, primary respiratory tract disease) causes. Serum samples for NT-proBNP assay were obtained at time of admission for each dog. Receiver-operating characteristic curves were constructed to determine the ability of serum NT-proBNP concentration to discriminate between cardiac and noncardiac causes of respiratory signs. RESULTS: Serum NT-proBNP concentration was significantly higher in dogs with cardiac versus noncardiac causes of respiratory signs. In dogs with primary respiratory tract disease, serum NT-proBNP concentration was significantly higher in those with concurrent pulmonary hypertension than in those without. A serum NT-proBNP cutoff concentration > 1,158 pmol/L discriminated between dogs with congestive heart failure and dogs with primary respiratory tract disease with a sensitivity of 85.5% and a specificity of 81.3%. CONCLUSIONS AND CLINICAL RELEVANCE: Measuring serum NT-proBNP concentration in dogs with respiratory signs helps to differentiate between congestive heart failure and primary respiratory tract disease as an underlying cause.

Doppler-derived deformation imaging in unsedated healthy adult dogs.

OBJECTIVES: To evaluate feasibility, repeatability and reproducibility (R&R) of Doppler-derived deformation imaging (DI) in healthy adult dogs. ANIMALS, MATERIALS AND METHODS: Forty-nine dogs underwent physical examination, ECG, blood pressure measurement and echocardiography. Doppler-derived DI parameters obtained from six selected Regions of Interest (ROI) within the left ventricle (LV) were: strain (S), systolic strain rate (SSR), strain rate E wave (SRE), and strain rate A wave (SRA). The averages of the six ROIs were calculated and labeled avS, avSSR, avSRE, and avSRA. Randomly selected dogs underwent two echocardiographic studies to evaluate intraoperator (n=14) and interoperator (n=17) variability. RESULTS: DI data were obtained in 87.2% of dogs and 77.2% of ROIs. Compared to controls, avSSR was significantly reduced in Doberman Pinchers (DP) and it was increased in dogs < 30 kg, compared to dogs > 30 kg. The intraoperator Coefficient of Variability (CV) for some ROIs was greater than 15% but for averaged measurements it was < or = 5.0%. Interoperator CV varied widely but were all < 15% for avSSR, avS, and avSRA. CONCLUSIONS: The CV for Doppler-derived DI varied widely. Averaging values from multiple ROIs improved R&R. DI may help elucidate differences in LV mechanics between canine breeds.

A technique for in vitro culture of canine valvular interstitial cells.

OBJECTIVE: To develop a method for in vitro culture of canine valvular interstitial cells (VICs). ANIMALS, MATERIALS AND METHODS: Canine VICs were isolated from the distal third of the anterior mitral valve leaflet using an explant technique and maintained in cell culture. Molecular phenotyping of the cultured cells was performed using reverse transcription polymerase chain reaction and immunocytochemistry. RESULTS: Cells resembling fibroblasts migrated from canine mitral valve explants and were maintained in culture for up to eight passages. Establishment of the valve explant required collagen but once established, subsequent passages grew on non-coated plastic plates. At confluence the cultured cells exhibited the characteristic whorled pattern of fibroblasts in culture. The isolated valve cells expressed vimentin but not platelet endothelial cell adhesion molecule or von Willebrand's factor, consistent with the molecular phenotype of VICs. CONCLUSIONS: VICs can be readily isolated from canine mitral valve leaflets and successfully maintained in culture using standard culture techniques. The described techniques permit the study of bioactive VICs in a controlled environment and may be a useful in vitro model for investigation of cellular and molecular alterations associated with canine chronic degenerative valve disease.

Endovascular retrieval of embolized jugular catheter fragments in three dogs using a nitinol gooseneck snare.

Two dogs were referred to the Kansas State University Veterinary Medical Teaching Hospital for pulmonary arterial embolization and one to Washington State University Veterinary Teaching Hospital for right heart embolization of jugular catheter fragments. Endovascular retrieval of foreign bodies was accomplished under general anesthesia in all three cases. Although the incidence of, and complications associated with catheter embolization in dogs are unknown, it appears that they can be safely and easily retrieved with a nitinol gooseneck snare.

Electrocardiographic and echocardiographic evidence of atrial dissociation.

A 4-year-old Boxer dog with a history of ventricular premature contractions was evaluated for anorexia. An electrocardiogram revealed atrial dissociation and an echocardiogram supported simultaneous mechanical atrial systole with the ectopic atrial electrical activity. This case and the supporting images provide further credence to the existence of atrial dissociation.

Percutaneous occlusion of a muscular ventricular septal defect with an Amplatzer muscular VSD occluder.

Ventricular septal defects are a relatively common congenital cardiac disease that, when severe, can be associated with substantial morbidity and mortality. Several minimally invasive methods of repair have been described in the human literature. This report describes the first case of percutaneous closure of a naturally occurring muscular septal defect using an Amplatzer occluder in a dog affected by concurrent pulmonic stenosis. Based on this experience catheter-based occlusion of muscular ventricular septal defects is a feasible option in dogs. Further studies are necessary to identify the attributes and limitations of the technique.