Amara H. Estrada

Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study)

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

Effect of azotemia on serum N-terminal proBNP concentration in dogs with normal cardiac function: A pilot study

OBJECTIVES To evaluate amino-terminal pro-B type natriuretic peptide (NT-proBNP) concentration in dogs with renal dysfunction and normal cardiac structure and function. ANIMALS Eight dogs with renal disease, 23 healthy control dogs. METHODS Serum NT-proBNP concentration was measured in healthy dogs and dogs with renal disease using an ELISA validated for use in dogs. Affected dogs were eligible for inclusion if renal dysfunction was diagnosed based on urinalysis and serum chemistry, and if they were free of cardiovascular disease based on physical exam, systolic blood pressure, and echocardiography. RESULTS The geometric mean serum NT-proBNP concentration was significantly higher in dogs with renal disease (617 pmol/L; 95% CI, 260-1467 pmol/L) than in healthy control dogs (261 pmol/L; 95% CI, 225-303 pmol/L; P=0.0014). There was a modest positive correlation between NT-proBNP and BUN and creatinine. Median NT-proBNP concentration was not significantly different between groups when indexed to BUN (median NT-proBNP:BUN ratio; renal, 14.2, IQR, 3.93-17.7 vs. control, 16.3, IQR, 9.94-21.2; P=0.29) or creatinine (median NT-proBNP:creatinine ratio; renal, 204, IQR, 72.6-448 vs. control, 227, IQR, 179-308; P=0.67). CONCLUSION Dogs with renal disease had significantly higher mean serum concentration of NT-proBNP than control dogs. Renal function should be considered when interpreting NT-proBNP results as concentrations may be falsely elevated in dogs with renal dysfunction and normal cardiac function. The effect of renal disease was lessened by indexing NT-proBNP to BUN or creatinine. Future studies in dogs with both renal and heart disease are warranted.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study—A Randomized Clinical Trial

Background Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives Administration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia. Animals 360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. Methods Prospective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia. Results Median time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) (P = .012). Conclusions and Clinical Importance Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Assessment of cardiac output measurement in dogs by transpulmonary pulse contour analysis.

OBJECTIVE To determine if metatarsal artery pressure (COmet) is comparable to femoral artery pressure (COfem) as the input for transpulmonary pulse contour analysis (PiCCO) in anesthetized dogs, using the lithium dilution method (LiDCO) as a standard for cardiac output (CO) measurement. DESIGN Prospective randomized study. SETTING University research laboratory. ANIMALS Ten healthy purpose-bred mixed breed dogs were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, and CO. INTERVENTIONS The CO was measured using LiDCO and PiCCO techniques. Animals had their right femoral and left distal metatarsal artery catheterized for proximal (COfem) and distal (COmet) PiCCO analysis, respectively. Measurements were obtained from each animal during low, normal, and high CO states by changing amount of inhalant anesthetics and heart rate. Measurements were converted to CO indexed to body weigh (CI(BW) =CO/kg) for statistical analysis. Agreement was determined using Bland and Altman analysis and concordance correlation coefficients. MEASUREMENTS AND MAIN RESULTS Thirty paired measurements were taken. The LiDCO CI(BW) (± SD) was 68.7 ± 30.3, 176.0 ± 53.0, and 211.1 ± 76.5 mL/kg/min during low, normal, and high CO states, respectively. There was a significant effect of CI(BW) state on bias and relative bias with COmet (P<0.001 and P=0.003, respectively). Bias of the COmet method (± SD) was -116.6 (70.5), 20.1(76.4), and 91.3 (92.0) mL/kg/min at low, normal, and high CI(BW), respectively. Bias of the COfem (± SD) was -20.3 (19.0), 8.6 (70.9), and -2.9 (83.0) mL/kg/min at low, normal, and high CI(BW) , respectively. The mean relative bias for COfem was -6.7 ± 44% (limits of agreements: -81.2 to 67.9%). CONCLUSION Compared with lithium dilution, the pulse contour analysis provides a good estimation of CO, but requires femoral artery catheterization in anesthetized dogs.

Tissue Doppler evaluation of ventricular synchrony

Tissue Doppler imaging (TDI) is a new echocardiographic method for analyzing global as well as segmental myocardial function. The purpose of this paper is to introduce readers to the techniques of TDI with specific attention to the utility of TDI in the evaluation of ventricular synchronization.

Cardiac Evaluation of Clinically Healthy Captive Maned Wolves (Chrysocyon brachyurus)

Abstract The objective of this project was to determine radiographic vertebral heart sizes and electrocardiographic (ECG) and echocardiographic measurements in healthy anesthetized maned wolves (Chrysocyon brachyurus). The wolves, housed at the White Oak Conservation and Smithsonian National Zoo Conservation and Research Centers, were being anesthetized for annual examinations. Cardiac auscultation, thoracic radiographs, a standard 6-lead ECG, and echocardiography were performed on the wolves while they were under general anesthesia. Thirteen maned wolves were evaluated: five males and eight females. Mean age was 6.4 ± 4.4 years (range, 2–13 years). Mean weight was 26 ± 2.95 kg (range, 22–32 kg). Low-grade systolic murmurs were auscultated in three of 13 maned wolves. Evaluation of ECGs revealed a sinus rhythm, with a QRS morphology, and mean electrical axis similar to domestic canines. Radiographic evaluation revealed a mean vertebral heart size of 8.27 ± 0.48 (range, 7.9–8.6). In addition, the cardiac silhouette was seen to elongate, with an increase in sternal contact in older wolves. Echocardiography showed that mitral valve degenerative changes and insufficiency is likely common in older wolves. Visualization of physiologic regurgitation across the mitral and pulmonary valves was common in wolves of all ages. Left ventricular measurements were similar to those reported for healthy dogs, and several variables correlated well with body weight. Two wolves were found to have one to three heartworms in the right pulmonary artery, and degenerative mitral valve disease was determined in maned wolves older than 6 years of age. All of the wolves in this study were on heartworm preventative and tested negative for heartworm antigen at their annual examinations. The results of this study provide reference information for use in the cardiac evaluation of anesthetized maned wolves.

Stem‐cell therapy for dilated cardiomyopathy: a pilot study evaluating retrograde coronary venous delivery

OBJECTIVE To evaluate retrograde coronary venous stem-cell delivery for Dobermanns with dilated cardiomyopathy. METHODS Retrograde coronary venous delivery of adipose-derived mesenchymal stem cells transduced with tyrosine mutant adeno-associated virus 2 to express stromal-derived factor-1 was performed in Dobermanns with dilated cardiomyopathy. Cases were followed for 2 years and electrocardiograms (ECG), echocardiograms and Holter monitoring were performed. RESULTS Delivery of cells was feasible in 15 of 15 dogs. One dog died following the development of ventricular fibrillation 24 hours after cell delivery. The remaining 14 dogs were discharged the following day without complications. Echocardiographic measurements of left ventricular size and function showed continued progression of disease. On the basis of Kaplan-Meier product limit estimates, median survival for dogs following stem-cell delivery was 620 days (range of 1-799 days). When including only the occult-dilated cardiomyopathy population and excluding those dogs already in congestive heart failure, median survival was 652 days (range of 46-799 days). CLINICAL SIGNIFICANCE Retrograde venous delivery of tyrosine mutant adeno-associated virus 2-stromal-derived factor-1 adipose-derived mesenchymal stem cells appears safe. Stem-cell therapy in dogs with occult-dilated cardiomyopathy does not appear to offer advantage compared to recently published survival data in similarly affected Dobermanns.

ELECTROCARDIOGRAPHY IN TWO SUBSPECIES OF MANATEE (TRICHECHUS MANATUS LATIROSTRIS AND T. M. MANATUS)

Abstract Electrocardiographic (ECG) measurements were recorded in two subspecies of awake, apparently healthy, wild manatees (Trichechus manatus latirostris and T. m. manatus) undergoing routine field examinations in Florida and Belize. Six unsedated juveniles (dependent and independent calves) and 6 adults were restrained in ventral recumbency for ECG measurements. Six lead ECGs were recorded for all manatees and the following parameters were determined: heart rate and rhythm; P, QRS, and T wave morphology, amplitude, and duration; and mean electrical axis (MEA). Statistical differences using a t-test for equality of means were determined. No statistical difference was seen based on sex or subspecies of manatees in the above measured criteria. Statistical differences existed in heart rate (P = 0.047), P wave duration (P = 0.019), PR interval (P = 0.025), and MEA (P = 0.021) between adult manatees and calves. Our findings revealed normal sinus rhythms, no detectable arrhythmias, prolonged PR and QT intervals, prolonged P wave duration, and small R wave amplitude as compared with cetacea and other marine mammals. This paper documents the techniques for and baseline recordings of ECGs in juvenile and adult free-living manatees. It also demonstrates that continual assessment of cardiac electrical activity in the awake manatee can be completed and can be used to aid veterinarians and biologists in routine health assessment, during procedures, and in detecting the presence of cardiac disease or dysfunction.

Successful closure of left-to-right patent ductus arteriosus in three dogs with concurrent pulmonary hypertension.

Closure of reversed patent ductus arteriosus (PDA) is generally accepted to be contraindicated due to case based evidence of worsened outcomes, but little is known about closure of left-to-right PDA with concurrent pulmonary hypertension (PH). This report describes three dogs presenting with varying severity of PH and clinical signs, all with documented left-to-right PDA. The PDA was closed in each case; either by surgical ligation or transarterial device occlusion, and follow up was available for a minimum of 8 months. Every case had a successful outcome with improvement or resolution of PH and associated clinical signs.

Effect of routine cardiovascular catheterization on cardiac troponin I concentration in dogs

OBJECTIVE To determine changes in cardiac troponin I concentration (cTnI) associated with cardiovascular catheterization in dogs. ANIMALS, MATERIALS AND METHODS cTnI was measured after transarterial coil embolization of patent ductus arteriosus (PDA), balloon valvuloplasty (BV), and pacemaker implantation (PACE). Dogs undergoing ovariohysterectomy (OHE) were used as a control, with 15 animals in each group. Blood for the cTnI assay was collected at baseline (T0), at 5h (T5), 24h (T24) and 10 days (T240) post-procedure. The effects of age, duration and difficulty of the procedure were evaluated. RESULTS There was no difference in cTnI concentration at T0 for any of the groups. There was a significant increase in cTnI concentration for BV and PACE, but not PDA at T5 and T24. PACE at T24 and T240 also had higher cTnI than control. Dogs with longer procedure times had significantly higher concentration of cTnI. There was no correlation between the difficulty of the procedure or peri-procedure complications and cTnI. CONCLUSION cTnI increased during some cardiovascular catheterization procedures, but returned to normal values at 24-240 h. Patients undergoing long catheterization procedures have increased risk for myocardial injury, but this was not related to short-term prognosis.