Veterinary echocardiographers' preferences for left atrial size assessment in cats: the BENEFIT project.

INTRODUCTION/OBJECTIVES: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in cats have not been systematically investigated. The primary aim of this prospective exploratory study was to investigate echocardiographers' preferences concerning LA size assessment in cats. A secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles. ANIMALS, MATERIALS, AND METHODS: An online survey instrument was designed, verified, and distributed globally to veterinary echocardiographers. RESULTS: A total of 655 veterinary echocardiographers from six continents and 54 countries, working in specialty practice (56%) and in general practice (38%), provided data. Linear two-dimensional (2D) technique was favored by most echocardiographers (n = 612) for LA size assessment. Most commonly, respondents combined linear 2D with subjective assessment (n = 227), while 209 used linear 2D-based methods alone. Most echocardiographers using linear 2D-based methods preferred the right parasternal short-axis view and to index the LA to the aorta (Ao). Approximately 10% of the respondents obtained LA dimensions from a right parasternal long-axis four-chamber view. Approximately one-third of echocardiographers that made linear measurements from 2D echocardiograms shared the same preferences regarding cat position, acquisition view, indexing method and time point identification for the LA measurement. The responses were comparably homogeneous across geographic location, level of training, years performing echocardiography, and type of practice. DISCUSSION/CONCLUSION: Most veterinary echocardiographers assessed LA size in cats using linear 2D echocardiography from a right parasternal short-axis view, and indexed LA to Ao. Respondents' preferences were similar over geographic, demographic, and professional backgrounds.

Veterinary echocardiographers' preferences for left atrial size assessment in dogs: the BENEFIT project.

INTRODUCTION/OBJECTIVES: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in dogs have never been systematically investigated. The primary aim of this international survey study was to investigate echocardiographers' preferences for LA size assessment in dogs. The secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles. ANIMALS, MATERIALS, AND METHODS: An online survey instrument was designed, verified, and distributed globally to the veterinary echocardiographers. RESULTS: A total of 670 echocardiographers from 54 countries on six continents completed the survey. Most echocardiographers (n = 621) used linear two-dimensional (2D)-based methods to assess LA size, 379 used subjective assessment, and 151 used M-mode-based methods. Most commonly, echocardiographers combined linear 2D-based methods with subjective assessment (n = 222), whereas 191 used linear 2D-based methods alone. Most echocardiographers (n = 436) using linear 2D-based methods preferred the right parasternal short-axis view and indexed the LA to the aorta. Approximately 30% (n = 191) of the echocardiographers who performed linear measurements from 2D echocardiograms shared the same preferences regarding dog position, acquisition view, indexing method, and identification of the time-point used for the measurement. The responses were comparably homogeneous across geographic location, training level, years of performing echocardiography, and type of practice. DISCUSSION/CONCLUSION: Most veterinary echocardiographers assessed LA size in dogs using linear 2D echocardiography from a right parasternal short-axis view, and by indexing the LA to the aorta. The respondents' preferences were similar across geographic, demographic, and professional backgrounds.

Advanced imaging in an adult dog with anomalous origin of the left coronary artery from the pulmonary artery and extensive collateral coronary circulation.

A three-year-old, spayed female, Bichon Frise was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery, a rare congenital coronary artery defect which has only been reported in two other dogs. Echocardiography was initially performed, though the final diagnosis was made with angiography and computed tomography angiography. An extensive network of collateral coronary circulation allowed for communication between the dilated, tortuous right coronary artery, and the anomalous left coronary artery. Though collateral circulation likely prolonged the patient's life, it is suspected that coronary steal phenomenon and chronic myocardial ischemia ultimately led to fatal ventricular arrhythmias. The dog died suddenly at the age of six, three years after initial diagnosis.

Use of physical examination, electrocardiography, radiography, and biomarkers to predict echocardiographic stage B2 myxomatous mitral valve disease in preclinical Cavalier King Charles Spaniels.

INTRODUCTION: Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD). Dogs with stage B2 MMVD benefit from medication. OBJECTIVES: To develop (1) breed-specific cut-offs for individual screening tests and (2) predictive models utilizing physical examination (PE), ECG, radiograph, and blood-based biomarker variables in combination for identification of echocardiographic stage B2 MMVD in preclinical CKCS. ANIMALS: Adult, preclinical CKCS not receiving cardiac medications (N = 226). MATERIALS AND METHODS: Prospective, cross-sectional study. Enrolled CKCS underwent PE, ECG, radiography, Doppler blood pressure measurement, echocardiography, and biomarker testing. Dogs were grouped by MMVD stage using echocardiography only. The discriminatory ability of individual tests to identify stage B2 was assessed, and prediction models were developed using variables derived from four 'tests' (PE, ECG, radiography, and biomarkers). RESULTS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and radiographic vertebral heart size (VHS) had the best discriminatory ability of individual diagnostic tests to differentiate stage A/B1 CKCS from stage B2, with an area under the curve (AUC) of 0.855 and 0.843, respectively. An NT-proBNP ≥1138 pmol/L or a VHS ≥11.5 had high specificity for predicting stage B2 (90.1% and 90.6%, respectively). Prediction models incorporating variables from multiple tests had better discriminatory ability than single tests. The four-test prediction model had an AUC of 0.971. Three and two-test models had AUCs ranging between 0.925-0.959 and 0.895-0.949, respectively. CONCLUSIONS: Both NT-proBNP and VHS have good utility for predicting echocardiographic stage B2 MMVD in CKCS as individual tests. Prediction models incorporating multiple test variables have superior discriminatory ability.

Echocardiographic measurement of the mitral valve in normal Cavalier King Charles spaniels: repeatability, optimal future study methods, and preliminary reference intervals.

INTRODUCTION/OBJECTIVES: Cavalier King Charles spaniels (CKCS) are ideal candidates for longitudinal study of myxomatous mitral valve (MV) disease and stage B1 clinical trials; however, the optimization of MV measurement acquisition and repeatability must be better defined to realize this potential. Additionally, breed-specific reference ranges for CKCS MV measurements are lacking. Study objectives were to assess measurement repeatability and define optimal methods for the longitudinal study of echocardiographic MV anatomy and to define preliminary, two-dimensional echocardiographic reference ranges for MV measurements in CKCS. ANIMALS: Forty CKCS between 10 and 24 months old. MATERIALS AND METHODS: Pre- and post-sedation two-dimensional echocardiographic images optimized for the MV were obtained. The length, width, and area of the anterior and posterior leaflets and the diameter of the MV annulus at end-diastole and end-systole were measured. Measurement repeatability was assessed using % coefficient of variation and repeatability coefficients. RESULTS: Intraoperator repeatability was best for the operator with previous MV measurement experience, with comparable results for the experienced operator measuring the second operator's images, mimicking a core echocardiography laboratory setting. Except for MV annulus diameter at end-systole, sedation had no significant effect on any MV measurements, nor did it impact measurement repeatability. Preliminary, breed-specific reference ranges were defined for the population, with CKCS often noted to have a larger annular diameter at end-systole than end-diastole. CONCLUSIONS: Optimal methods for longitudinal study of the MV in CKCS have been proposed, as have two-dimensional preliminary echocardiographic reference ranges for CKCS MV measurements. The MV annulus in CKCS may differ from other breeds.

Feasibility and clinical utility of transvenous intracardiac echocardiography in conscious, sedated horses.

INTRODUCTION/OBJECTIVES: Intracardiac echocardiography (ICE) is a method of obtaining echocardiographic images with a steerable ultrasound catheter placed within the heart via a venous or arterial approach. The objectives of this study were to assess the feasibility of a 5-10 MHz, 8 French, 90 cm ICE catheter to evaluate cardiac structures and function in standing, sedated horses, and describe standard views in this species. ANIMALS: Ten apparently healthy horses weighing 458.1-618.2 kg from a university teaching herd. MATERIALS AND METHODS: Each horse had a physical examination, transthoracic echocardiography, and ICE performed through a 10 French introducer percutaneously placed in the right jugular vein in the proximal third of the neck with continuous ECG monitoring using telemetry. RESULTS: Three intracardiac echocardiography positions (cranial right atrium, mid right atrium, and right ventricle) with seven views were described with the associated 2D, pulse wave Doppler, continuous wave Doppler, color Doppler, and M-mode image acquisition standardized by referencing the intracardiac positions and common landmarks. The positions were confirmed with simultaneous transthoracic echocardiography. The procedure was well tolerated with only mild, occasional ventricular, and supraventricular arrhythmias that resolved with intracardiac echocardiography catheter repositioning. CONCLUSIONS: Intracardiac echocardiography is feasible, safe, and allows for the acquisition of diagnostic images in conscious, sedated horses.

Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers.

INTRODUCTION: Screening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. OBJECTIVE: To investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. ANIMALS, MATERIALS AND METHODS: All dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. RESULTS: Heart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. CONCLUSIONS: Both NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.

Prediction of clinically important acquired cardiac disease without an echocardiogram in large breed dogs using a combination of clinical, radiographic and electrocardiographic variables.

INTRODUCTION: Large breed (LB) dogs develop dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD). Echocardiography is required for a definitive diagnosis but is not always available. Our objective was to assess the clinical utility of thoracic radiographs alone and in combination with physical examination and electrocardiography findings for the prediction of clinically important DCM or MMVD in LB dogs. ANIMALS: Four hundred fifty-five client-owned dogs ≥20 kg with concurrent thoracic radiographs and echocardiogram. MATERIALS AND METHODS: Medical records were reviewed and stored thoracic radiographs and echocardiographic images were measured to classify dogs as normal heart size (NHS), preclinical DCM, clinical DCM, preclinical MMVD (with cardiomegaly), clinical MMVD, or equivocal. Dogs with preclinical MMVD, without cardiomegaly, were classified as NHS. Vertebral heart size (VHS) and vertebral left atrial size (VLAS) were measured. Receiver operating characteristic curves and prediction models were derived. RESULTS: Prevalence of MMVD (39.3%) was higher than the prevalence of DCM (24.8%), though most MMVD dogs (67.0%) lacked cardiomegaly and were classified as NHS for analysis. The area under the curve for VHS to discriminate between NHS and clinical DCM/MMVD or preclinical DCM/MMVD was 0.861 and 0.712, respectively, while for VLAS, it was 0.891 and 0.722, respectively. Predictive models incorporating physical examination and electrocardiography findings in addition to VHS/VLAS increased area under the curve to 0.978 (NHS vs. clinical DCM/MMVD) and 0.829 (NHS vs. preclinical DCM/MMVD). CONCLUSIONS: Thoracic radiographs were useful for predicting clinically important DCM or MMVD in LB dogs, with improved discriminatory ability when physical examination abnormalities and arrhythmias were accounted for.

Hybrid balloon valvuloplasty for management of severe mitral stenosis in four symptomatic, adult dogs.

Four adult dogs weighing <10 kg presented for the evaluation of severe mitral valve stenosis with clinical signs. Owing to the size of the dogs, a hybrid surgical and interventional approach was utilized for balloon valvuloplasty. A left lateral thoracotomy was performed to allow direct entry through the left atrial wall. Transesophageal echocardiography was utilized for the entirety of the procedure in all dogs, and fluoroscopy was additionally used in two dogs. One dog had mild to moderate intra-operative bleeding from the left atrial wall during the procedure, but no other intra-operative complications were observed. No dogs developed a clinically relevant amount of worsened mitral regurgitation. Based on mitral leaflet mobility and transmitral flow profiles, there was perceived improvement in all four dogs. One dog died 6 h after extubation due to respiratory arrest. The remaining dogs survived to discharge and had resolution of clinical signs at home and discontinuation of heart failure medications. One dog died of an unknown cause at five months and another developed atrial fibrillation, and the owners elected to euthanize at ten months after the procedure. One dog continues to do well six months after the procedure as of the time of this writing. Hybrid balloon valvuloplasty can be a viable management option for small breed dogs with severe mitral stenosis exhibiting clinical signs, and both transesophageal echocardiography and fluoroscopy can be used intra-operatively to assist in successful procedural outcomes.

Epicardial pacemaker implantation and outcome in eight pet ferrets (Mustela putorius furo).

INTRODUCTION/OBJECTIVES: Minimal information exists regarding epicardial pacemaker (EP) implantation in pet ferrets (Mustela putorius furo). The objectives were to describe the indications, surgical technique, and outcome of EP implantation in ferrets for the treatment of advanced atrioventricular block (AVB). ANIMALS, MATERIALS, AND METHODS: Eight client-owned ferrets presenting to five veterinary referral centers. Signalment, physical exam findings, diagnostic tests, anesthesia protocols, surgical implantation techniques, postoperative treatment plans, and EP interrogations were reviewed. Intra- and postoperative, minor and major, and EP-related complications were established. Descriptive statistics were performed to report complication rates. Survival analyses were performed. RESULTS: All ferrets had advanced AVB: 3/8 had high-grade second-degree and 5/8 had third-degree. The primary clinical signs were collapse and weakness. Seven EP were implanted via a transdiaphragmatic approach and one via a left intercostal thoracotomy. Intraoperative complications occurred in 2/8 ferrets, both major. One ferret with severe comorbidities died during general anesthesia. Postoperative pacemaker-related complications were minor: inappropriate sinus beat sensing in 2/8 and occasional muscle fasciculations in 1/8. Two ferrets were alive at the time of manuscript submission, at 10 and 21 months postoperatively. The overall median survival time was 24 months. CONCLUSIONS: Implantation of EP was performed successfully in most ferrets for treatment of advanced AVB and was well tolerated. Ferrets with advanced AVB may experience resolution of clinical signs associated with their cardiac disease following EP implantation. Additional studies are warranted to investigate the effects of epicardial pacing on survival times in this species.

Utility of transesophageal echocardiography for transcatheter occlusion of patent ductus arteriosus in dogs: influence on the decision-making process.

BACKGROUND: Appropriate device selection for transcatheter occlusion of patent ductus arteriosus (PDA) is essential to procedural success. OBJECTIVES: To determine if transesophageal echocardiography (TEE) influences device selection for PDA occlusion and to report benefits, limitations, and complications associated with TEE. ANIMALS: Twenty-two client-owned dogs with left-to-right shunting PDA. METHODS: PDA dimensions were obtained via transthoracic echocardiography (TTE) and then TEE followed by angiography. Based solely on information from TTE and angiography, an initial device type and size were selected. After initial device selection, TEE measurements were disclosed and changes in device selection were recorded. After device release, angiography, TEE, or both were performed to assess occlusion. RESULTS: An Amplatz canine duct occluder (ACDO) was securely positioned and released in 21 dogs and an embolization coil was deployed in 1 dog. Based on TEE evaluation, initial selected device type was unchanged but ACDO size was changed in 3 dogs. TEE was utilized throughout the procedure allowing real time visualization of device deployment, release and assessment of closure in 17 dogs. No complications occurred related to TEE. Complete PDA closure was achieved in all dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: TEE provided anatomic information regarding PDA morphology that closely approximated angiographic ductal dimensions while aiding in device deployment, release and confirmation of closure. We conclude that TEE provides complementary anatomical and intraprocedural information and is well tolerated in dogs.

Palliative combined cutting and high-pressure balloon valvuloplasty in six dogs with severe, symptomatic subaortic stenosis.

INTRODUCTION/OBJECTIVES: Severe subaortic stenosis (SAS) is a congenital heart defect in dogs that often results in clinical signs and reduced survival. The objective of this study was to describe characteristics of dogs with severe, symptomatic SAS who underwent combined cutting and high-pressure balloon valvuloplasty (CB/HPBV). ANIMALS, MATERIALS, AND METHODS: Retrospective description of the clinical characteristics, CB/HPBV procedural deviations from reported methodology and outcomes in a series of six client-owned dogs with severe, symptomatic SAS. RESULTS: Breeds included two each of Newfoundland, Golden retriever, and German shepherd. Median age was 10.1 months (range: 5-72.3 months), and median weight was 25.5 kg (range: 21.8-36.4 kg). Before CB/HPBV, clinical signs were present in all dogs; four were managed for congestive heart failure (CHF). Three dogs had concurrent congenital heart disease. Median Doppler-estimated left ventricular outflow tract pressure gradient was pre-operatively 149.7 mmHg (range: 89.9-254.7 mmHg) and post-operatively 134.1 mmHg (range: 83.9-181.2 mmHg). Median aortoseptal angle was steep at 136° (range: 109-143°). Clinical improvement was documented in all dogs, based on temporary discontinuation of diuretics and/or owner-perceived reduction in clinical signs. At the time of writing, three dogs had died suddenly, one was euthanized because of recurrence of clinical signs, and one died in CHF. Median survival time was 26.4 months after procedure (range: 6.3-45.8 months). One dog remained alive at 44 months after procedure. CONCLUSIONS: Palliative CB/HPBV is a potential therapeutic option for dogs with severe, symptomatic SAS complicated by concurrent congenital heart disease, arrhythmias, or CHF.

Transcatheter atrial septal defect closure with the Amplatzer atrial septal occluder in 13 dogs: short- and mid-term outcome.

BACKGROUND: Transcatheter atrial septal defect (ASD) closure in the dog was first reported in 2005. OBJECTIVES: Describe the technique and both short- and mid-term outcome of transcatheter ASD closure with the Amplatzer atrial septal occluder (ASO). ANIMALS: Thirteen client-owned dogs with ASD. METHODS: Records of the initial 13 dogs in which transcatheter ASD closure was attempted at Texas A&M University were reviewed. RESULTS: All dogs had hemodynamically relevant septum secundum ASD. Two dogs had concurrent congenital abnormalities. ASOs were deployed in 13 dogs and released in 12. Eleven were released by a right jugular approach and 1 by a transatrial approach through a right lateral thoracotomy. Transthoracic echocardiographic estimates of ASD size were 14.0 + or - 5.4 mm (mean + or - 1 standard deviation) with a range of 7-22 mm. Accidental right atrial release occurred in 1 dog and embolization after release occurred in 2 dogs. Transcatheter ASD closure was successful in 10 dogs. Transthoracic color Doppler echocardiography the day after ASD closure indicated complete occlusion in 5 dogs, trivial to mild residual shunting in 4 dogs, and moderate residual shunting in 1 dog. Follow-up echocardiograms (mean of 12.4 + or - 7.4 months postprocedure) were available for 9 dogs. There was no residual ASD shunting in 6 dogs. In 3 of the 5 dogs with postoperative residual shunting it was judged to be decreased and hemodynamically unimportant relative to the dogs' postoperative evaluations. The mean length of event-free survival in the 10 dogs that underwent successful transcatheter ASD closure was 22.2 + or - 10.2 months.

Artificial cardiac pacemaker placement in dogs with a cohort of myocarditis suspects and association of ultrasensitive cardiac troponin I with survival.

INTRODUCTION: Artificial cardiac pacemakers (APs) are a common treatment for symptomatic bradyarrhythmias in dogs, some of which may be triggered by underlying myocarditis. Severely elevated cardiac troponin I (cTnI) concentrations support a diagnosis of myocarditis. The association of ultrasensitive-cTnI (US-cTnI) concentration with survival in a large cohort of dogs receiving APs is not described. ANIMALS, MATERIALS, AND METHODS: The study included 110 dogs receiving APs over a 5-year period. Medical records were retrospectively reviewed to characterize the entire population receiving APs, with further analysis in dogs with preprocedural US-cTnI concentrations (n = 64) classified as normal/group 1 (n = 11), mildly to moderately elevated/group 2 (n = 27), and severely elevated/myocarditis suspects/group 3 (n = 26). RESULTS: Median survival time was 1079 days for the entire population, 1167 days for group 2, 949 days for group 3, and not met in group 1. There was not a statistically significant difference in survival between group 2 and group 3. Overall, US-cTnI had a mild, negative association with survival. Age had a stronger negative association. Infectious etiologies were identified in a minority of group 3 cases. A possible association between severely elevated US-cTnI and a sudden death outcome was noted. CONCLUSIONS: The negative association of US-cTnI with survival outcomes was mild, with age having a larger effect. Although a sudden death outcome may be seen more commonly in myocarditis suspects, group 3 survival time was similar to that of the entire canine population. Plausible infectious causes of myocarditis were infrequently identified.

Quantitative assessment of two- and three-dimensional transthoracic and two-dimensional transesophageal echocardiography, computed tomography, and magnetic resonance imaging in normal canine hearts.

INTRODUCTION: The objective of the study was to evaluate the accuracy of two- and three-dimensional (2D, 3D) transthoracic echocardiography (TTE), 2D transesophageal echocardiography, and computed tomography angiography (CTA) compared with cardiac magnetic resonance imaging (CMR) in normal dogs and to assess repeatability of 2D and 3D TTE for the assessment of left ventricular (LV) and left atrial (LA) dimensions. ANIMALS: The study was performed on six healthy dogs. MATERIALS AND METHODS: Transthoracic echocardiography, transesophageal echocardiography, CTA, and CMR were performed on each dog. Right ventricular (RV) and LV volumes (in systole and diastole), ejection fraction (EF), and LA and right atrial (RA) volumes were assessed. Repeatability and intrarater and interrater measurements of variability were quantified by average coefficient of variation (CV) for 2D and 3D TTE. RESULTS: No clinically relevant differences in LV volume were detected between CMR and all modalities. Importantly, 3D TTE had the lowest CV (6.45%), correlated with (rs = 0.62, p = 0.01), and had the highest overlap in distribution with CMR (OVL >80%). Left ventricular EF and LA size via CTA compared best with CMR and RV and RA volumes were best estimated by 3D TTE. Assessment of LV and LA volumes via 3D TTE had moderate repeatability (15-21%) compared with LV M-mode measurements and 2D LA-to-aortic ratio (<10%), respectively. For LV size, interrater CV for 3D TTE (19.4%) was lower than 2D TTE (23.1%). CONCLUSIONS: Measurements of LV, RV, and RA volumes via 3D TTE and LA volume and LV EF assessed by CTA compared best with CMR. Three-dimensional echocardiography had lower interrater and intrarater CV compared with 2D TTE.

Transarterial ductal occlusion with the Amplatzer vascular plug in 31 dogs.

BACKGROUND: Transarterial ductal occlusion with the Amplatzer vascular plug was first reported in dogs by Hogan et al in 2005. HYPOTHESIS: Use of the Amplatzer vascular plug is a safe, efficacious method of patent ductus arteriosus (PDA) occlusion. ANIMALS: Thirty-one client-owned dogs with PDA. METHODS: Records of 31 dogs in which transarterial occlusion of PDA with an Amplatzer vascular plug was attempted were reviewed. RESULTS: All dogs had a type II PDA, with 27 dogs having type IIA morphology and 4 dogs having type IIB morphology. Appropriate device deployment was achieved in 29 of 31 dogs. Postdeployment angiography in 21 dogs documented complete occlusion in 10 dogs, trivial residual flow in 5 dogs, mild residual flow in 2 dogs, moderate residual flow in 3 dogs, and severe residual flow in 1 dog. Transthoracic color Doppler echocardiography documented complete occlusion in 22 dogs, whereas 2 dogs had trivial residual flow, 2 dogs had mild residual flow, 2 dogs had mild to moderate residual flow, and 1 dog had severe residual flow. Of the 7 dogs with residual flow, 2 had complete occlusion 2-4 months postoperatively, 1 had moderate residual flow 1 month postoperatively, and 4 were lost to follow-up. One dog required a larger device than was able to be deployed through the largest sheath placed in the femoral artery. Pulmonary embolization of the device occurred in 1 dog. CONCLUSION: We conclude that ductal occlusion with an Amplatzer vascular plug is a safe and efficacious therapy for PDA in dogs.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

A factor X-activating cysteine protease from malignant tissue.

A proteolytic procoagulant has been identified in extracts of human and animal tumors and in cultured malignant cells. It directly activated Factor X but its similarity to other Factor S-activating serine proteases was not clear. This study describes work done to determine whether this enzyme, cancer procoagulant, is a serine or cysteine protease. Purified cancer procoagulant from rabbit V2 carcinoma was bound to a p-chloromercurialbenzoate-agarose affinity column and was eluted with dithiothreitol. The initiation of recalcified, citrated plasma coagulation activity by cancer procoagulant was inhibited by 5 mM diisopropylfluorophosphate, 1 mM phenylmethylsulfonylfluoride, 0.1 mM HgCl2, and 1 mM iodoacetamide. Activity was restored in the diisopropylfluorophosphate-, phenylmethylsulfonylfluoride-, and HgCl2-inhibited samples by 5 mM dithiothreitol; iodoacetamide inhibition was irreversible. Russell's viper venom, a control Factor X-activating serine protease, was not inhibited by either 0.1 mM HgCl2 or 1 mM iodoacetamide. The direct activation of Factor X by cancer procoagulant in a two-stage assay was inhibited by diisopropylfluorophosphate and iodoacetamide. Diisopropylfluorophosphate inhibits serine proteases, and an undefined impurity in most commercial preparations inhibits cysteine proteases. Hydrolysis of diisopropylfluorophosphate with CuSO4 and imidazole virtually eliminated inhibition of thrombin, but cancer procoagulant inhibition remained complete, suggesting that cancer procoagulant was inhibited by the undefined impurity. These results suggest that cancer procoagulant is a cysteine endopeptidase, which distinguishes it from other coagulation factors including tissue factor. This and other data suggest that neoplastic cells produce this unique cysteine protease which may initiate blood coagulation.

Genetic Analysis of Soybean Plant Introductions with Resistance to Phytophthora sojae.

ABSTRACT Phytophthora sojae, which causes Phytophthora root and stem rot of soybean, is a serious disease worldwide and is managed primarily by deploying cultivars with resistance. Thirty-two soybean plant introductions (PIs), all but three of which were from South Korea, were proposed as new sources of single-gene resistance to P. sojae. The objective of this study was to characterize the inheritance of resistance to P. sojae in these PIs. Twenty-two soybean populations from crosses of these PIs and the susceptible cv. Williams were inoculated with P. sojae OH17 (vir 1b, 1d, 2, 3a, 3b, 3c, 4, 5, 6, 7), and OH25 (vir 1a, 1b, 1c, 1k, 7). These isolates were selected because they are virulent on soybeans with all known Rps genes and many Rps gene combinations. Thirteen of the twenty-two populations had consistent segregation responses following inoculations between the two generations. In two PIs, resistance was conferred by two genes to OH17 and three genes to OH25. Resistance to both isolates was conferred by a single gene in PI 398440 although the individual families were not resistant to the same isolates. The data suggest that six of the populations have three-Rps gene combinations as previously proposed, while another four may have either a novel Rps gene or a four-Rps gene combination. Based on this phenotypic analysis, novel and uncharacterized Rps genes may be present in this material. More importantly, these PIs may serve as sources of novel Rps genes that can be used to more effectively manage Phytophthora root and stem rot.

Molecular Marker Analysis of Soybean Plant Introductions with Resistance to Phytophthora sojae.

ABSTRACT Molecular analysis of sources of resistance to plant pathogens should expedite and confirm novel gene discovery and consequently the development of disease resistant cultivars. Recently, soybean plant introductions (PIs) were identified that contain putative novel Rps genes for resistance to Phytophthora sojae. The number of resistance genes that confer resistance to P. sojae isolates OH17 (1b,1d,2,3a,3b,3c,4,5,6,7) and OH25 (1a,1b,1c,1k,7) was then determined in several of the PIs. The objective of this study was to determine if the Rps genes present in these PIs were associated with eight described Rps loci that have been mapped on soybean molecular linkage groups F, G, J, and N. Nine F(2:3) soybean populations were genotyped with simple sequence repeat (SSR) markers linked to previously mapped Rps loci. The nine PI populations all had SSR markers associated (P < 0.01) with resistance to P. sojae isolate OH17 in the Rps1 region. Rps1c is a likely candidate in eight PIs but novel genes may also be possible, while novel genes may confer resistance in one PI to P. sojae isolate OHI7. Two or more Rps genes, including some that are potentially novel, confer resistance to P. sojae isolate OH25 in eight of the populations. However, based on the response to these two isolates, virulence already exists for at least some of the novel genes identified in this study.