AN EXPANSION ON DIAGNOSTIC AND PROGNOSTIC MARKERS IN DOGS WITH ACUTE AND CHRONIC HEART FAILURE

In the last decades, human and veterinary literature has increasingly highlighted the importance of heart failure (HF) as a complex clinical syndrome. By its definition, HF is a condition in which the heart is unable to maintain sufficient organ perfusion to meet the body’s needs. Consequent hemodynamic derangements turn into increased sympathetic nervous system activity and neurohormonal dysregulation, which progressively lead to inflammation, oxidative stress and multi-organ damage and dysfunction. The aim of the present project is to achieve a better understanding of the diagnostic and prognostic significance of different markers related to the primary aspects of the HF syndrome in dogs: neurohormonal dysregulation and multi-organ damage. The present project consists of four distinct investigations. The first study evaluated the urinary aldosterone-to-creatinine ratio (UAldo:C), a potential indicator of patient’s overall renin-angiotensin-aldosterone system (RAAS) activity, in healthy dogs and dogs with naturally occurring myxomatous mitral valve disease (MMVD) and investigated the relationships between this parameter and clinical, echocardiographic and laboratory variables. Urinary aldosterone-to-creatinine ratio was not significantly different among healthy and MMVD dogs of any stages. However, individual factors such as breed, sex, age and therapy appeared to affect aldosterone concentrations. Chihuahuas and intact females showed the highest values of UAldo:C among breeds and reproductive states respectively. These results suggested that population-based reference values of this parameter might not be representative of the RAAS activity of the single patient, and an individual monitoring may be more appropriate. In humans, the influence of sex on RAAS activity has been primarily related to female sexual hormones. In particular, aldosterone levels have been showed to rise during high progesterone states. The second study aimed to investigate the relationship between progesterone and aldosterone and NT-proBNP in sexually intact Chihuahua bitches, measuring these hormones in anoestrus and dioestrus (ie, low and high progesterone state respectively). Serum progesterone and urinary aldosterone were significantly higher in dioestrus compared to anoestrous, and serum progesterone showed a moderate positive correlation with urinary aldosterone and UAldo:C. No effects of progesterone on NT-proBNP were found. These results suggested the existence of a progesterone-aldosterone relationship in canine species, indicating that sex and phase of reproductive cycle should be taken into account when interpreting aldosterone concentrations. The third study focused on Chihuahua, an increasingly widespread breed predisposed to MMVD and whose most common causes of death are hearth diseases and low respiratory tract disorders. The study aimed to determine preliminary breed-specific reference intervals for plasma NT-proBNP and UAldo:C in healthy Chihuahuas, and to assess sex differences in these parameters in a single-breed population. Moreover, the study attempted to confirm the effect of Chihuahua breed on UAldo:C. Median values of NT-proBNP were similar or lower to those reported in other breeds in previous studies. Reference interval and inter-individual coefficient of variation of this parameter were wide, but in line with those previously reported in other small-size breed dogs. The currently available non-breed specific cut-off of 900 pmol/L appeared to be valid for Chihuahuas, although exceeding values in normal subjects might occur even in this breed. In contrast to previous studies, no sex differences in NT-proBNP were detected. Reference interval of UAldo:C was much wider than that reported in a previous study, but breed and sex appeared to play a relevant role in this discrepancy. The fourth study investigated another aspect of the HF syndrome, that is the multi-organ damage and, in particular, the dilemma of worsening renal function and decongestion in acute HF. The study retrospectively assessed the prognostic value of renal parameters, haemoconcentration and selected clinical variables in dogs hospitalized for left-sided congestive heart failure (CHF). Worsening renal function (creatinine increase ≥ 0.3 mg/dl) and electrolytes concentrations did not impact on survival. In contrast, haemoconcentration at discharge was associated with a lower risk of all-cause and cardiac mortality, supporting the importance of adequate decongestion suggested by recent human literature. Moreover, dogs with prior CHF hospitalizations showed an increased risk of cardiac mortality. This association could be related to the potential multi-organ deleterious effects of each acute decompensation, to the fact that patients with acute CHF reoccurrence are “sicker”, and to a combination of both. The authors believe that the present project contributed to better understand the diagnostic value of different markers of the HF syndrome in dogs, as well as to improve their interpretation, providing novel insights for future research in this field.