What is the more effective strategy: activation or inhibition of myosin?
Papp Zoltán, Sárkány Fruzsina, Ráduly Arnold, Pásztor Dávid,
Máté Balázs István, Tóth Attila, Borbély Attila
Debreceni Egyetem, Általános Orvostudományi Kar,
Klinikai Fiziológiai Tanszék, Debrecen
The function of the myosin molecule is closely related to cardiac systolic and diastolic performances. In the absence of side-effect-free inotropic drugs, the development of direct myosin activators and direct myosin inhibitors evolves with considerable professional interest. Omecamtiv mecarbil is the most studied representative of direct myosin activators and has recently been shown to be effective in the GALACTIC-HF large randomized clinical trial. However, the accumulation of knowledge regarding less favourable effects of the agent – and the similar behaviour of the second-generation danicamtiv – means that rapid clinical introduction of direct myosin activators is not expected. As a result of the action of direct myosin activators, systolic duration increases – and consequently diastolic duration decreases – the rates of ventricular contractions and relaxations are slowed, which together raise the possibility of diastolic dysfunction. Direct myosin inhibitors (mavacamten and aficamten) may have a role in the treatment of hypertrophic cardiomyopathy, due to their negative inotropic effects. As far as we know, the reduction of hypercontractility in the latter condition can slow down the hypertrophic transformation of the heart, which may prevent invasive treatments of hypertrophic cardiomyopathy (septal myectomy, septal ablation, heart transplantation). Nevertheless, many questions remain to be answered regarding the development and use of myosin inhibitor drugs. Data so far suggest that myosin inhibition, in a well-chosen patient population, may become part of everyday practice sooner than a positive inotropic treatment based on myosin activation.
ISSUE: CARDIOLOGIA HUNGARICA | 2023 | VOLUME 53, ISSUE 4
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