Novel approaches to management of congestive heart failure in dogs and cats

Abstract

Congestive heart failure (CHF) is the most commonly treated condition in veterinary cardiology as it is the sequela of a multitude of cardiovascular diseases. This thesis reviews current practices in veterinary CHF therapeutics and explores novel approaches to therapy through examining three aspects of this topic: the differences in pimobendan pharmacokinetics and pharmacodynamics between dogs and cats; the role of multi-modal therapy in dogs with CHF; and the role of the brain natriuretic peptide (BNP) system in dogs with CHF. Pimobendan metabolism and treatment effects were reduced in cats compared to dogs, bringing to question its role in feline CHF. In contrast, its effects were readily detected in dogs; thus, echocardiogram-based therapeutic monitoring may be possible in this species. Pimobendan was well-tolerated when used with benazepril, spironolactone, and frusemide in dogs with CHF due to myxomatous mitral valve disease (MMVD). Though the natural course of disease was similar to that of other treatment regimens, this regimen appeared to offer some survival benefits – a finding that supports the call for larger trials. To evaluate the BNP system as a novel therapeutic target, assay development to identify specific BNP1-32 and its assessment in healthy dogs undergoing acute intravascular expansion were undertaken. BNP1-32 was detectable via mass spectrometry; however, sample preparation posed a significant challenge in determining its concentrations in plasma. Fluid loading did not reliably activate the BNP system in healthy dogs. When exogenous BNP1-32 was given to dogs with CHF due to MMVD, evidence of successful receptor-ligand interaction was found; yet no biological effects were detected, thus raising suspicion of peripheral BNP resistance in these dogs. Together, these findings provided further insights into CHF therapeutics and identified numerous avenues for further research.