Cardiology Resident CVCA - Cardiac Care for Pets Leesburg, Virginia, United States
Abstract:
Background: Inotropic support is a mainstay of congestive heart failure therapy and an area of novel drug discovery. Omecamtiv mecarbil (OM) is a sarcomere modulator that targets the catalytic S1 domain of cardiac myosin. Pimobendan and OM support systolic function through two specific mechanisms of the actin-myosin binding complex; however, their synergistic action is unknown. Hypothesis/
Objectives: We hypothesize that combination therapy of OM and pimobendan will be safe and effective in increasing canine myocardial systolic function. Animals: 6 healthy adult purpose-bred dogs
Methods: A single-blinded, placebo-controlled, crossover pharmacodynamic study was carried out. Five echocardiographic timepoints were compared. On day 1, each dog received vehicle (echo 1) followed by intravenous pimobendan bolus (0.15mg/kg; echo 2) followed by a 30-day washout period. Vehicle was repeated (echo 3) followed by OM (0.25mg/kg IV bolus and 0.25mg/kg/hr IV CRI x 15 minutes; echo 4), followed by the final treatment with dual therapy (OM 0.25mg/kg/hr IV CRI plus pimobendan at 0.15mg/kg IV).
Results: Change in echocardiographic values from same-day vehicle control were calculated, normality tested and compared with the corresponding parametric (one-way ANOVA and Tukey’s multiple comparisons test) or non-parametric equivalent (Friedman’s and Dunn’s multiple comparisons test). Left ventricular ejection fraction was significantly increased (P< 0.006) with dual therapy compared to OM or pimobendan. Conclusions and clinical importance: Dual therapy was well-tolerated and improved systolic function compared to pimobendan or OM alone. Future studies in dogs with cardiovascular disease are indicated.
