Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial.

AIMS: Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction. METHODS AND RESULTS: We studied the effects of danicamtiv on LV and LA function in non-clinical studies (ex vivo: skinned muscle fibres and myofibrils; in vivo: dogs with heart failure) and in a randomized, double-blind, single- and multiple-dose phase 2a trial in patients with stable HFrEF (placebo, n = 10; danicamtiv, n = 30; 50-100 mg twice daily for 7 days). Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P < 0.05) and LA emptying fraction (+10.7%, P < 0.05). In patients with HFrEF (mean age 60 years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment-emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations ≥2000 ng/mL) increased stroke volume (up to +7.8 mL, P < 0.01), improved global longitudinal (up to -1.0%, P < 0.05) and circumferential strain (up to -3.3%, P < 0.01), decreased LA minimal volume index (up to -2.4 mL/m2 , P < 0.01) and increased LA function index (up to 6.1, P < 0.01), when compared with placebo. CONCLUSIONS: Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre-clinical findings of direct activation of LA contractility.

Prevalence of endoparasites in captive snakes of Kerala, India

The objective of the study was to evaluate the status of parasitic infections in captive snakes of Kerala. Faecal samples were collected from captive snakes of State Museums and Zoos of Thrissur and Thiruvananthapuram. Parasites were screened by direct smear, sedimentation, simple floatation and Shaether's sugar floatation method. Fortynine snakes from 15 species were screened and 35 (71.4%) were found to be positive. While 80% of the snakes from Thrissur were found to be positive for parasitic infections, 70.6% of the samples from Thiruvananthapuram zoo were positive. Strongyloides sp. was the most prominent infection, accounting for 25.7% of all infections, followed by Capillaria sp. (22.8%) and Strongyles (20%). The preliminary investigation of captive Green Anaconda samples from Thiruvananthapuram zoo revealed mites, non-sporulated Coccidia of the genus Eimeria sp. and Cryptosporidium sp. It is understood that most of the infections of the captive snakes were acquired through the feeding and handling of the snakes, therefore periodical sampling is needed for both the snakes and their prey.