Daniel F. Hogan

Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats.

BACKGROUND Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/E(a)). METHODS NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP (1) was higher (median and inter-quartile [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218; P=0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94). CONCLUSIONS NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.

Multicenter Evaluation of Plasma N-Terminal Probrain Natriuretic Peptide (NT-pro BNP) as a Biochemical Screening Test for Asymptomatic (occult) Cardiomyopathy in Cats

BACKGROUND B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. HYPOTHESIS/OBJECTIVES Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. ANIMALS One hundred and fourteen normal, healthy cats; 113 OCM cats. METHODS Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM, NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33; P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = -0.27; P = .004). Area under ROC curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive. CONCLUSIONS AND CLINICAL IMPORTANCE Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression.

Transarterial Coil Embolization of Patent Ductus Arteriosus in Small Dogs with 0.025-Inch Vascular Occlusion Coils: 10 Cases

Patent ductus arteriosus (PDA) is the most common congenital cardiac disease in the dog and generally leads to severe clinical signs, including left-sided congestive heart failure. Historically, definitive treatment consisted of surgical ligation; however, the use of vascular occlusion devices by minimally invasive techniques has gained popularity in veterinary medicine during the past decade. Adequate vascular access is a major limiting factor for these minimally invasive techniques, precluding their use in very small dogs. The clinical management of PDA with 0.025-in vascular occlusion coils in a minimally invasive transarterial technique in 10 dogs is described. The dogs were small (1.38 +/- 0.22 kg), were generally young (6.70 +/- 5.74 months), and had small minimal ductal diameters (1.72 +/- 0.81 mm from angiography). Vascular access was achieved, and coil deployment was attempted in all dogs with a 3F catheter uncontrolled release system. Successful occlusion, defined as no angiographic residual flow, was accomplished in 8 of 10 (80%) dogs. Successful occlusion was not achieved in 2 dogs (20%), and both dogs experienced embolization of coils into the pulmonary arterial tree. One of these dogs died during the procedure, whereas the other dog underwent a successful surgical correction. We conclude that transarterial PDA occlusion in very small dogs is possible with 0.025-in vascular occlusion coils by means of a 3F catheter system and that it represents a viable alternative to surgical ligation. The risk of pulmonary arterial embolization is higher with this uncontrolled release system, but this risk may decrease with experience.

Secondary prevention of cardiogenic arterial thromboembolism in the cat: the double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT)

OBJECTIVES To determine if clopidogrel administration is associated with a reduced likelihood of recurrent cardiogenic arterial thromboembolism (CATE) in cats compared to aspirin administration. Secondary aims were to determine if clopidogrel administration had an effect on the composite endpoint of recurrent CATE and cardiac death and to identify adverse effects of chronic clopidogrel or aspirin therapy. ANIMALS Seventy-five cats that survived a CATE event. METHODS Multicenter, double-blind, randomized, positive-controlled study. Cats were assigned to clopidogrel (18.75 mg/cat PO q 24 h) or aspirin (81 mg/cat PO q 72 h). Kaplan-Meier survival curves were created for each endpoint and the log rank test performed to compare treatment groups with respect to time to event and the likelihood of the event occurring. RESULTS The mean age of all cats was 8.0 ± 3.5 yr and 57/75 (76%) were male (p < 0.001); 62/75 (83%) were mixed breed with the remainder including Persian, Abyssinian, American Shorthair, Bengal, Birman, Himalayan, Maine Coon, Ragdoll, Snowshoe, and Sphynx breeds. Only 15% (11/75) of cats had a history of heart disease recorded prior to the CATE event. Clopidogrel administration was associated with significantly reduced likelihood of recurrent CATE compared to aspirin (p = 0.024) and had a longer median time to recurrence [443 (95% CI 185-990) days vs. 192 (95% CI 62-364) days, respectively]. Clopidogrel was also associated with a significantly reduced likelihood of the composite endpoint of recurrent CATE or cardiac death (p = 0.033) with a longer median time to event [346 (95% CI 146-495) days vs. 128 (95% CI 58-243) days]. CONCLUSIONS Clopidogrel administration significantly reduces the likelihood of recurrent CATE compared with aspirin in cats; both drugs were well tolerated.

In vitro evaluation of the effect of hypothermia on coagulation in dogs via thromboelastography.

OBJECTIVE To evaluate the effect of temperature alterations on in vitro coagulation in healthy dogs using thromboelastography (TEG). DESIGN In vitro study. SETTING University teaching hospital. ANIMALS Six healthy purpose-bred laboratory dogs. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Thromboelastograph tracings were created daily for all test subjects and used to generate control values for R, K, α, and MA. Control values were compared to test samples incubated at 42, 39, 36, 33, 30, and 27°C. At temperatures ≤ 30°C, a significant increase in K values and a significant decrease in the α values were noted. There were no significant differences detected for R and MA among any of the test temperatures. CONCLUSIONS Hypothermia results in in vitro coagulation changes in healthy dogs as determined by whole blood analysis using TEG. The data suggest that while clots may form more slowly at decreased temperatures, the ultimate strength of the clot appears unaffected.Objective To evaluate the effect of temperature alterations on in vitro coagulation in healthy dogs using thromboelastography (TEG). Design In vitro study. Setting University teaching hospital. Animals Six healthy purpose-bred laboratory dogs. Interventions None. Measurements and Main Results Thromboelastograph tracings were created daily for all test subjects and used to generate control values for R, K, α, and MA. Control values were compared to test samples incubated at 42, 39, 36, 33, 30, and 27°C. At temperatures ≤ 30°C, a significant increase in K values and a significant decrease in the α values were noted. There were no significant differences detected for R and MA among any of the test temperatures. Conclusions Hypothermia results in in vitro coagulation changes in healthy dogs as determined by whole blood analysis using TEG. The data suggest that while clots may form more slowly at decreased temperatures, the ultimate strength of the clot appears unaffected.

Transcatheter closure of patent ductus arteriosus in a dog with a peripheral vascular occlusion device

A 4-month-old, intact female mixed-breed dog presented to the Purdue University Veterinary Teaching Hospital for evaluation of a cardiac murmur. A large left-to-right patent ductus arteriosus (PDA) was diagnosed and interventional correction was achieved with a commercially available peripheral vascular occlusion device (VOD). The VOD is composed of a nitinol wire mesh and is similar in composition and shape to a commercially available human PDA occluder, however, it can be deployed through smaller delivery catheters and is much less expensive. The product and procedural details of the device are described.

Treatment of acute epistaxis secondary to guttural pouch mycosis with transarterial nitinol vascular occlusion plugs in three equids

CASE DESCRIPTION 2 horses and 1 pony were evaluated for right-sided (1 horse and the pony) and left-sided (1 horse) acute epistaxis of 1 days to 1 months duration. CLINICAL FINDINGS Endoscopic examination of the 3 equids revealed that the hemorrhage originated from the right maxillary artery in 2 equids and from the left internal carotid artery in the third. Mycosis of the auditory tube diverticulum (guttural pouch) was detected in all 3 equids. TREATMENT AND OUTCOME All 3 equids underwent surgery, and transarterial nitinol intravascular plugs were placed to occlude affected blood vessels. All equids survived for a long period (ie, a minimum of 1 to 2 years) and returned to their previous use. All had complete regression of clinical signs of guttural pouch mycosis without additional medical treatment. CLINICAL RELEVANCE The use of transarterial nitinol intravascular plugs appeared to be an effective alternative to other techniques for the treatment of epistaxis secondary to guttural pouch mycosis, including transarterial occlusion devices such as embolization coils.

Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine

Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for assessing farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency domain analyses may provide a sensitive and reliable measure of affective states and stress-mediated changes in sympathetic and parasympathetic tones. The aim of this research was to define low (LF) and high frequency (HF) power spectral ranges using pharmacological autonomic blockade, and to examine HRV and BPV parameter changes in response to atropine and propranolol in swine. Ten, 13-week old, barrows (n=6) and gilts (n=4) underwent surgery to place an intra-cardiac electrode and a blood pressure catheter attached to a biotelemetric transmitter; pigs had a 3-week recovery period prior to data collection. Each pig was subjected to administration of 4 intravenous (i.v.) drug treatments: a control treatment, 3 mL of saline, and 3 blockade treatments; 0.1 mg/kg of atropine, 1.0 mg/kg of propranolol, and .1 mg/kg of atropine together with 1.0 mg/kg of propranolol. All treatments were delivered by injection in the jugular vein with a minimum of 48 h between individual treatments. Behavior, ECG and blood pressure data were recorded continuously for a total of 1h, from 30 min pre-injection to 30 min post-injection. For data analyses, two 512-beat intervals were selected for each treatment while the pig was lying and inactive. The first interval was selected from the pre-injection period (baseline), and the second was selected between 10 and 30 min post-injection. Time and frequency domain (power spectral density) analyses were performed on each data interval. Subsequent, LF and HF bands from the power spectral densities were defined based on general linear and regression analyses. The HRV and BPV were computed with a covariate (baseline) factorial analysis of treatment by sex interaction, and day of injection, with mixed models and Tukeys post-hoc tests. The best-fit range for LF was 0.0-0.09 Hz, and HF was 0.09-2.0 Hz (r²: 0.41 and 0.43, respectively). Propranolol and saline injections led to a greater overall total power and overall higher inter-beat interval, HF and LF power. Atropine led to a dominant sympathovagal balance of the cardiac activity in pigs. In addition, atropine led to an increase in LF power of both systolic and diastolic blood pressures in gilts suggesting vagal tone mediation of BPV. The understanding of autonomic regulation of HRV and BPV in domestic swine facilitates our ability to detect and quantify stress responses, and broadens its application in assessing farm animal welfare.

Antithrombotic effect of enoxaparin in clinically healthy cats: a venous stasis model.

BACKGROUND Systemic arterial thromboembolic events are a serious complication of cardiac disease in cats. OBJECTIVES To determine if enoxaparin induces an antithrombotic effect in cats at a dosage of 1 mg/kg SC q12h and if this antithrombotic effect is predicted by anti-Xa activity. ANIMALS Fourteen clinically healthy cats were divided into 3 groups: control (4 cats), treated and assessed at 4 hours (5 cats), and treated and assessed at 12 hours (5 cats). METHODS A venous stasis model was used and the extent of thrombus formation estimated by measuring thrombus weight and accretion of 125I-fibrinogen. Plasma anti-Xa activity was measured in treated cats. RESULTS There was a significant reduction in thrombus formation in the 4 h group compared with control (median weight, 0.000 versus 0.565mg/mm, P < .01; median % 125I-fibrinogen accretion, 0.0 versus 42.0%, P < .01). There was a reduction in thrombus formation in the 12 h group (median weight, 0.006 mg/mm, P = .09; median % 125I-fibrinogen accretion, 3.83%, P = .09) but this reduction was not significant. The median percent thrombus inhibition for treated cats was 100.0% at 4 hours and 91.4% at 12 hours. Plasma anti-Xa activity was not significantly correlated with thrombus formation. CONCLUSIONS AND CLINICAL IMPORTANCE This pilot study demonstrates that enoxaparin, when administered at a dosage of 1 mg/kg SC q12h, produces an antithrombotic effect in a venous statsis model in clinically healthy cats. Furthermore, this study demonstrates that anti-Xa activity is a poor predictor of enoxaparins antithrombotic effect.

Dose determination of fondaparinux in healthy cats

OBJECTIVE To establish practical doses and administration frequencies of fondaparinux for cats that would approximate human therapeutic peak and trough plasma anti-factor Xa activities for thromboprophylaxis (TP) and thrombosis treatment (TT) protocols. ANIMALS 6 healthy adult purpose-bred cats. PROCEDURES Dosage protocols for TP and TT were selected on the basis of a single compartment pharmacokinetic model incorporating data from humans but modified to account for the higher body weight-normalized cardiac output of cats. Fondaparinux was administered at 0.06 mg/kg, SC, every 12 hours (TP) for 7 days in one session, and 0.20 mg/kg, SC, every 12 hours (TT) for 7 days in another, with a minimum of 1 week separating the sessions. Plasma anti-factor Xa activity was measured before fondaparinux administration (day 1) and at 2 (peak) and 12 (trough) hours after drug administration on days 1 and 7. Platelet aggregation and thromobelastographic (TEG) parameters were also measured 2 hours after drug administration on day 7. RESULTS Peak plasma anti-factor Xa activities on day 7 for TP (median, 0.59 mg/L; range, 0.36 to 0.77 mg/L) and TT (median, 1.66 mg/L; range, 1.52 to 2.00 mg/L) protocols were within therapeutic ranges for humans. However, only the TP protocol achieved trough anti-factor Xa activity considered therapeutic in humans (median, 0.19 mg/L; range, 0.00 to 0.37 mg/L) on day 7. There were significant changes in the TEG parameters at peak for the TT protocol, suggesting a hypocoagulable state. No significant changes in platelet aggregation were evident for either protocol. CONCLUSIONS AND CLINICAL RELEVANCE A fondaparinux dosage of 0.06 or 0.20 mg/kg, SC, every 12 hours, was sufficient to achieve a peak plasma anti-factor Xa activity in cats that has been deemed therapeutic in humans. This study provided preliminary data necessary to perform fondaparinux dose-determination and clinical efficacy studies.