The heart’s efficiency is impaired with the new heart failure drug omemcamtiv mecarbil, according to a new study from Tromsø.
American researchers recently presented omemcamtiv mecarbil as a safe and effective new drug for treating heart failure with reduced ejection fraction. In their placebo-controlled COSMIC-HF trial, omemcamtiv mecarbil improved the heart’s pump function by prolonging systolic ejection time. However, a study by PhD candidate Jens Petter Bakkehaug and colleagues at UiT The Arctic University of Norway indicates that the drug does more harm than good for failing hearts.
The paper presented in Bakkehaug’s doctoral thesis found increased oxygen wastage with omemcamtiv mecarbil in a clinically relevant pig model of left ventricular dysfunction. The drug resulted in a shortened diastole and decreased filling of the left ventricle between heart beats. Because of this, omemcamtiv mecarbil did not increase the stroke volume despite the beneficial effect on ejection fraction. The results were further confirmed in mouse hearts.
– Billions of dollars are at stake when new drugs are developed. Therefore, the kind of industry independent research carried out at UiT The Arctic University of Norway is important. Our results show that omemcamtiv mecarbil must be studied extensively before it can ever get into sales, Bakkehaug states in a press release.
In another study, Bakkehaug and colleagues found that combined treatment with dobutamine and ivabradine optimizes left ventricular pump function in acute and life-threatening heart failure. Dobutamine strengthens each contraction and increases the stroke volume of the heart. However, the drug also increases the heart rate and thus contributes to an increased risk of life-threatening arrhythmias. Ivabradine was shown to counteract the adverse effects of dobutamine on heart rate, without any detrimental effect on stroke volume. The study was conducted on pig hearts.
Thesis: Novel inotropic strategies for treating acute heart failure: A large animal study on cardiac function and energetics
Candidate: Jens Petter Bakkehaug
Time and place: February 16, 2017, UiT The Arctic University of Norway
Bakkehaug, J. P., Kildal, A. B., Engstad, E. T., Boardman, N., Næsheim, T., Rønning, L., Aasum, E., Larsen, T. S., Myrmel, T. & How, O. J. (2015). The myosin activator omecamtiv mecarbil increases myocardial oxygen consumption and impairs cardiac efficiency mediated by resting myosin ATPase activity. Circulation: Heart Failure, CIRCHEARTFAILURE-114.
Bakkehaug, J. P., Naesheim, T., Torgersen Engstad, E., Kildal, A. B., Myrmel, T., & How, O. J. (2016). Reversing dobutamine‐induced tachycardia using ivabradine increases stroke volume with neutral effect on cardiac energetics in left ventricular post‐ischaemia dysfunction. Acta Physiologica, 218(2), 78-88.