Evaluation of Pimobendan and N‐Terminal Probrain Natriuretic Peptide in the Treatment of Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease in Dogs

Abstract

Background: Pimobendan is a positive inotrope and vasodilator that may be useful in the treatment of pulmonary hypertension (PHT) secondary to degenerative mitral valve disease.Hypothesis: Pimobendan decreases the severity of PHT measured echocardiographically and improves quality-of-life scores. Changes in N-terminal probrain natriuretic peptide (NT-proBNP) concentrations will reflect improvement in severity of PHT.Animals: Ten client-owned dogs with peak tricuspid regurgitant flow velocity (TRFV) !3.5 m/s. Methods: Prospective short-term, double-blinded, crossover design, with a long-term, open-label component. Short term, dogs were randomly allocated to receive either placebo or pimobendan (0.18-0.3 mg/kg PO q12 h) for 14 days. After a 1-week washout, they received the alternative treatment for 14 days, followed by pimobendan open-label for 8 weeks.Results: Short-term comparison: peak TRFV decreased in all dogs on pimobendan compared with placebo from a median of 4.40 (range, 3.2-5.6) to 3.75 (range, 2.4-4.8) m/s (P o .0001). NT-proBNP concentration decreased after treatment with pimobendan from a median of 2,143 (range, 450-3,981) to 1,329 (range, 123-2,411) pmol/L (P 5 .0009). All dogs improved their quality-of-life score (P 5 .006). In the long-term comparisons, peak TRFV decreased in all dogs from a median of 4.28 (range, 3.5-5.7) to 3.52 (range, 2.4-5.0) m/s (P o .0001). No significant changes in NT-proBNP or quality-of-life scores were detected.Conclusions and Clinical Importance: Pimobendan lowered severity of measurable PHT, improved quality-of-life scores, and decreased NT-proBNP concentrations short-term. Long term, only the reduction in TRFV was maintained.

A prospective, randomized, double‐blind, placebo‐controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease

“…On the other hand, clinically irrelevant systemic hypotension was seen more frequently in human patients taking S/V than in those taking enalapril, but S/V did not significantly alter SAP over time in the dogs of our study 24. Sacubitril/valsartan and related drugs have been shown to be a safe and effective treatment for systemic hypertension in humans and have been shown to delay the progression of chronic and proteinuric kidney diseases 46, 47, 48, 49, 50. Increased NEP concentrations are present in human patients with end‐stage renal dysfunction, suggesting an additional indication for use of S/V in patients with renal disease 51.…”

“…A decrease in NT‐proBNP concentrations in the S/V group can be explained by the reasons described above, but these would not explain the decrease seen in the placebo group. Limited published information is available on the effect of pimobendan on plasma NT‐proBNP concentrations, but a study in dogs with MMVD and PH showed a significant decrease in plasma NT‐proBNP concentrations after short‐term pimobendan administration 46. Therefore, pimobendan potentially could have caused the decrease in plasma NT‐proBNP concentration in both groups.…”

“…Because of these beneficial effects that the NPs have on the cardiovascular and renal systems, drugs such as S/V may have important implications for cardiovascular‐renal disorders in dogs 19, 52. The addition of exogenous NPs to furosemide administration causes more profound diuresis and natriuresis and has the potential to allow for decreases in diuretic dosages, while preventing furosemide‐induced RAAS activation 40, 46, 53, 54. Future studies evaluating the concurrent use of S/V and furosemide are indicated in dogs.…”

Pulmonary Hypertension in the Dog

“…Increases in ANP and NT-pro-BNP were also mildly correlated with PAP in a canine model of acute PTE, but their diagnostic value was signifi cant only in the more severe cases with RV dilation or dysfunction [84]. NT-pro-BNP was also associated with PH in dogs with MMVD and its concentration decreased after pimobendan administration and associated improvement of clinical condition [85]. However, the predictive value of natriuretic peptides is considered low in dogs with PH and their increase can be considered a sign of RV overloading instead of PH itself [86].…”

“…It is approved for the treatment of heart failure in dogs with MMVD and DCM [44]. In one study it was effective in reducing TR velocity and NT-BNP in dogs with post-capillary PH, and this effect was maintained long term [85]. A possible explanation for this positive effect could be the increased expression of PDE-3 and PDE-5 in PH which can infl uence vascular reactivity [100].…”