Omecamtiv mecarbil evokes diastolic dysfunction and leads to periodic electromechanical alternans

Gábor Fülöp, Attila Oláh, Tamas Csipo, Árpád Kovács, Róbert Pórszász, Roland Veress, Balázs Horváth, László Nagy, Beáta Bódi, Miklós Fagyas, Solveig Lind Helgadottir, Viktor Bánhegyi, Béla Juhász, Mariann Bombicz, Daniel Priksz, Peter Nanasi, Béla Merkely, István Édes, Zoltán Csanádi, Zoltán PappTamás Radovits, Attila Tóth

Research output: Contribution to journalArticlepeer-review


Omecamtiv mecarbil (OM) is a promising novel drug for improving cardiac contractility. We tested the therapeutic range of OM and identified previously unrecognized side effects. The Ca2+ sensitivity of isometric force production (pCa50) and force at low Ca2+ levels increased with OM concentration in human permeabilized cardiomyocytes. OM (1 µM) slowed the kinetics of contractions and relaxations and evoked an oscillation between normal and reduced intracellular Ca2+ transients, action potential lengths and contractions in isolated canine cardiomyocytes. Echocardiographic studies and left ventricular pressure–volume analyses demonstrated concentration-dependent improvements in cardiac systolic function at OM concentrations of 600–1200 µg/kg in rats. Administration of OM at a concentration of 1200 µg/kg was associated with hypotension, while doses of 600–1200 µg/kg were associated with the following aspects of diastolic dysfunction: decreases in E/A ratio and the maximal rate of diastolic pressure decrement (dP/dtmin) and increases in isovolumic relaxation time, left atrial diameter, the isovolumic relaxation constant Tau, left ventricular end-diastolic pressure and the slope of the end-diastolic pressure–volume relationship. Moreover, OM 1200 µg/kg frequently evoked transient electromechanical alternans in the rat in vivo in which normal systoles were followed by smaller contractions (and T-wave amplitudes) without major differences on the QRS complexes. Besides improving systolic function, OM evoked diastolic dysfunction and pulsus alternans. The narrow therapeutic window for OM may necessitate the monitoring of additional clinical safety parameters in clinical application.

Original languageEnglish (US)
Article number24
JournalBasic Research in Cardiology
Issue number1
StatePublished - Dec 2021
Externally publishedYes


  • Ca sensitivity
  • Diastolic dysfunction
  • Heart failure
  • Inotropy
  • Omecamtiv mecarbil
  • Pulsus alternans

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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