Table 1.
Baseline demographic and echocardiographic characteristics.
Fig 1.
Isoproterenol increases heart rate and contractility and induces dynamic LVOT obstruction in cats with HCM.
Treatment with isoproterenol 0.04 μg/kg/min IV (A) augments heart rate, fractional shortening (FS) and LVOT gradient (n = 5, mean ± SD), (B) provokes mitral valve SAM and mitral/septal contact (LV = left ventricle cavity, MV = anterior leaflet mitral valve), (C) induces an LVOT pressure gradient (scale bar 0.5 m/s) and (D) mitral regurgitation.
Fig 2.
MYK-461 reduces contractility in feline HCM in an exposure-dependent manner.
(A) Study scheme depicting timing of echocardiograms (numbered) and administration of isoproterenol (iso) at constant dose and MYK-461 or vehicle as a ramp infusion. Timepoints with asterisks correspond to blood draws to measure plasma concentration of MYK-461. Timepoint 1: baseline following anesthesia; timepoint 2: stable isoproterenol; timepoints 3–6: stable isoproterenol with increasing MYK-461 dose; timepoint 7: stable MYK-461 dose without isoproterenol. (B) Decrease in contractility with MYK-461 treatment by M-mode echocardiography. (C) Before and after plot of FS in response to treatment with MYK-461 (n = 5) or vehicle (n = 3) in the absence of isoproterenol (*, p = 0.03 vs vehicle by unpaired t-test; **, p = 0.01 vs. pre-dose by paired t-test). (D) Linear correlation of FS with MYK-461 plasma concentration for timepoints 2–6 in the presence of isoproterenol (n = 3 cats, p<0.0001).
Fig 3.
Treatment with MYK-461 abolishes mitral valve SAM and reduces LVOT gradients in cats with HCM.
Treatment with MYK-461 abolishes (A) SAM and (B) LVOT obstruction induced by isoproterenol treatment. (C) Before and after plot of LVOT pressure gradient for cats treated with isoproterenol 0.04 μg/kg/min IV and either MYK-461 (n = 5) or vehicle (n = 3) (*, p = 0.038 vs. vehicle by unpaired t-test; **, p = 0.0007 vs. pre-dose by paired t-test). (D) Linear correlation of relative LVOT pressure gradient (normalized to values prior to MYK-461 treatment) with the plasma concentration of MYK-461 at timepoints 2–6 (n = 3 cats, p<0.0001).