Study to compare effects of a positive inotrope administered concurrently with a beta-blocker in ventricular Tachy-Paced dogs in mild heart failure

Dilated cardiomyopathy(DCM) is common in dogs and is characterized by dilation and impaired systolic function of the ventricles. Pimobendan, a positive inotrope, has been suggested to benefit DCM by reducing preload and afterload, providing positive inotropic support, reducing cardiac size and filling pressures. Beta-blockers are used to treat ventricular arrhythmias associated with DCM, although there is concern that decreased inotropy could be detrimental to ejection fraction (EF). Given need for multimodal treatments, combined use of pimobendan and beta-blockers could help to mediate the negative inotropy of beta-blockers. This pilot study aims to compare the echocardiographic EF of simultaneous administration of pimobendan and sotalol (beta-blocker) at veterinary dosages in a HF dog model. Seven beagle-dogs were induced into mild HF using a ventricular-tachy-pacing(VTP) model. Dogs received four different treatment regimens: control, pimobendan (0.2–0.3 mg/kg PO BID), sotalol (1-3 mg/kg PO BID), and a combination of pimobendan and sotalol for two-weeks each. Multiple methods of calculating EF via echocardiography were evaluated, including ejection fraction (Eft) and fractional shortening (FS) from M-mode and Simpson's method-of-discs (SimpsonsEF) measured from right parasternal long-axis view, and were recorded at baseline, day 3, 7, and 14. By day 14, echocardiographic data indicated administration of pimobendan resulted in a significant increase in EF compared to baseline (↑ Eft 19.3 ± 3 % ΔBL; ↑ FS 24.1 ± 3.9 %ΔBL; ↑ SimpsonsEF 28.9 %ΔBL). In contrast, sotalol showed a significant decrease in EF compared to baseline (↓ Eft 9.5 ± 6.8; ↓ FS 9.9 ± 8.2; ↓ Simpson's EF 19.1 ± 9.5). The combination therapy of pimobendan and sotalol showed a non-significant increase in EF from baseline (↑ Eft 5.1 ± 5.5; ↑ FS 6.5 ± 6.7; ↑ SimpsonsEF 1.53 ± 9.5), but the change was similar to that of the control group (↑ Eft 3.1 ± 4.4; ↑ FS 4.2 ± 5.3; ↑ SimpsonsEF 3.0 ± 7.2), indicating that the change could be due to day-to-day variation. The study demonstrates that concurrent administration of a positive inotrope with a beta-blocker does not decrease cardiac function, as evidenced by no significant decrease in EF. In dogs with DCM that may benefit from beta-blocker therapy, pimobendan may be added to mitigate negative inotropic effects. This combination of therapies may allow clinicians to optimize treatment in complicated cases, warranting further investigation.