Pulmonary hypertension (PHT) is characterized by elevated pulmonary arterial pressure that results in clinical signs such as syncope, right-sided heart failure, and death. Pimobendan, a phosphodiesterase III inhibitor and calcium channel sensitizing agent causes positive inotropy and vasodilation, which may be advantageous in PHT. In humans, amino terminal-prohormone brain natriuretic peptide (NT-proBNP) levels reflect PHT disease severity.
The hypothesis of this study was pimobendan therapy would decrease the severity of PHT and improve patient's quality of life (QOL). The study was conducted as a prospective short-term, double-blinded, randomized, crossover design, with a long-term, open-label component. Ten client-owned dogs with a peak tricuspid regurgitant pressure gradient (TRPG) > 50 mmHg on echocardiogram and clinical signs such as cough, syncope, and ascites were enrolled. The etiology of the pulmonary hypertension was myxomatous atrioventricular valve disease in 8 of the dogs, and chronic pulmonary disease in 2. The dogs were examined on days 0, 14, 21, 35, and 91, with completion of a QOL questionnaire, NT-proBNP levels, thoracic radiographs, and echocardiography. In the 35-day short-term phase, dogs were allocated at random to receive either a placebo or pimobendan (0.18-0.3 mg/kg, PO q12h) for 14 days. Following a 1 week washout period, the dogs received the alternative treatment for 14 days. Following the 35 day short-term period all dogs received pimobendan for an 8 week period. Data were analyzed using a two period crossover design. Differences for each parameter were assessed by the appropriate F test and the significance level was set at p < 0.05.
Short-term comparison of pimobendan vs. placebo: Pimobendan resulted in a significant decrease in the peak TRPG (p=0.0061). 10/10 dogs had a decreased TRPG on pimobendan therapy in comparison to when they were on placebo, with a mean decrease of 16.37 ±12.89 mmHg. All dogs demonstrated a significant decrease in NT-proBNP levels (p=0.0023) while receiving pimobendan, with a mean difference of 708.8 ± 508.6 pmol/L. A significant improvement in the summed QOL score was noted with pimobendan therapy in 9/10 dogs (p=0.016).
Long-term comparison of day 0 vs. 91: The TRPG was significantly decreased at completion of the study (p=0.03). 9/10 dogs had a decreased TRPG, with a mean decrease of 14.0 ± 15.6 mmHg. No significant changes in NT-proBNP levels (p=0.34) or the summed QOL scores (p=0.41) were seen. These data suggest that pimobendan therapy is well tolerated in this small study population. Pimobendan therapy led to a short-term amelioration in clinical signs, a reduction in NT-proBNP levels, and a decreased TRPG. Failure to show an improvement in the clinical signs and NT-proBNP levels long-term may be due to the progressive nature of the underlying PHT, or the small sample size.