Clinical applications of cardiac myosin activators in the light of preclinical studies
█ Review
DOI: 10.26430/CHUNGARICA.2023.53.5.476
Authors:
Ráduly Arnold Péter1,2, Sárkány Fruzsina1, Kovács Máté Balázs1, Juhász Béla3, Horváth Balázs4, Szentandrássy Norbert5, Nánási Péter Pál5, Édes István5, Csanádi Zoltán2, Tóth Attila1, Papp Zoltán1, Priksz Dániel3, Borbély Attila1,2
1Debreceni Egyetem, Általános Orvostudományi Kar, Kardiológiai Intézet, Klinikai Fiziológiai Tanszék, Debrecen
2Debreceni Egyetem, Általános Orvostudományi Kar, Kardiológiai Intézet, Kardiológiai Tanszék, Debrecen
3Debreceni Egyetem, Farmakológiai és Farmakoterápiai Intézet, Debrecen
4Debreceni Egyetem, Általános Orvostudományi Kar, Élettani Intézet, Debrecen
5Debreceni Egyetem, Fogorvostudományi Kar, Fogorvosi Élettani és Gyógyszertani nem önálló Tanszék, Debrecen
Summary
There have been significant advances in the management of heart failure with reduced ejection fraction (HFrEF) over the last decade. However, the so-called positive inotropic agents, which directly correct the contractile dysfunction at the heart of the pathomechanism of the disease, have still not been a resounding success. The ideal positive inotropic agent does not increase myocardial energy demand and oxygen consumption. Unfortunately, the drugs used so far have not fully met these requirements. Direct modulation of the actin-myosin interaction by myosin activators is a new therapeutic target to enhance contractile force without the adverse side effects typical of previous agents. In clinical trials, the first such drug, omecamtiv mecarbil (OM), has not been introduced into clinical practice due to lack of adequate efficacy, despite initial positive results in phase III trials. Several preclinical studies have investigated the limiting factors for the applicability of this compound. However, the failure of OM has also stimulated the development of a new type of myosin activator, danicamtiv. Preclinical and clinical studies on danicamtiv are currently limited. The results to date are more encouraging for danicamtiv, but many more studies are needed to confirm this. Presumably, the future applicability of both candidates may be limited by their adverse effects on diastolic function.
ISSUE: CARDIOLOGIA HUNGARICA | 2023 | VOLUME 53, ISSUE 5
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