M. Lynne O'Sullivan

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

BACKGROUND Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS A total of 260 dogs in CHF because of MMVD. METHODS A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

Prospective Evaluation of NT‐proBNP Assay to Detect Occult Dilated Cardiomyopathy and Predict Survival in Doberman Pinschers

BACKGROUND Occult (asymptomatic) dilated cardiomyopathy (ODCM) is highly prevalent in Doberman Pinschers. HYPOTHESIS/OBJECTIVES Assess ability of NT-proBNP assay to detect ODCM and predict death. ANIMALS 155 asymptomatic Dobermans presenting for ODCM screening. METHODS Echocardiography, 24-hour Holter, and NT-proBNP assay were performed prospectively. Diagnosis was based on increased left ventricular end-systolic dimension, >50 ventricular premature complexes (VPCs), or both on Holter. Utility was evaluated using receiver-operating characteristic curves. Effect of age, weight, sex, disease status, VPCs, and NT-proBNP on survival was analyzed using Kaplan-Meier and Cox-proportional hazard analysis. RESULTS Seventy-three (47.1%) Dobermans were diagnosed with ODCM, including 31, 17, and 25 that met Holter, echocardiographic, or both criteria, respectively. Sensitivity of NT-proBNP > 457 pmol/L to detect these groups was 45.2, 76.5, and 96.0%, respectively. Combination of NT-proBNP and Holter to detect ODCM yielded sensitivity of 94.5%, specificity of 87.8%, and accuracy of 91.0%. Follow-up data were available for 78 Dobermans. The median survival time of Dobermans with > 50 VPCs (469 days), NT-proBNP > 900 pmol/L (284 days), or ODCM (474 days) was significantly (P < .0001) shorter than those with < 50 VPCs (1743 days), NT-proBNP < 900 pmol/L (1743 days), or without disease (1743 days). NT-proBNP concentration and disease status were independently predictive of all-cause mortality. CONCLUSIONS AND CLINICAL IMPORTANCE The combination of NT-proBNP assay and Holter detected ODCM with high accuracy. NT-proBNP and disease status were independently associated with survival. NT-proBNP assay identified Dobermans with high probability of increased LVIDs consistent with ODCM, and can facilitate pursuit of confirmatory diagnostic testing, such as echocardiography, in suspected Dobermans.

2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM.

Comparison of Computed Tomographic and Radiographic Popliteal Lymphangiography in Normal Dogs

OBJECTIVE To (1) describe computed tomographic (CT) popliteal lymphangiography; (2) compare the number of thoracic duct (TD) branches detected by CT and by radiography after popliteal lymphangiography; and (3) to compare the number of branches detected after left and right popliteal lymphangiography. STUDY DESIGN Experimental study. ANIMALS Adult dogs (n=6). METHODS A randomly selected popliteal lymph node was percutaneously injected with 12 L iodinated contrast medium through a 25-g butterfly catheter over 4-5 minutes. Lateral and ventrodorsal (VD) thoracic radiograph projections and thoracic CT were performed. The procedure was repeated using the contralateral lymph node after a 48-72 hours washout period. RESULTS One dog had TD branches visible on CT but not on radiographs. A significantly greater number of TD branches were observed with CT popliteal lymphangiography compared with lateral and VD radiographic popliteal lymphangiography (P=.003 and P<.001, respectively). The number of visible TD branches observed between the 6th thoracic and 1st lumbar vertebrae were not significantly different in these dogs (P=.146). A significant difference in number of TD branches observed was not found after left or right popliteal lymph node injection (P=.097). CONCLUSIONS CT popliteal lymphangiography consistently identified a greater number of TD branches when compared with radiographic popliteal lymphangiography. Injection of either popliteal lymph node resulted in the same number of TD branches being observed.