Optimizing cardiac efficiency and diastolic function in acute heart failure treatment

The investigation into novel inotropic treatments for acute heart failure reveals critical insights into the cardiovascular effects of Omecamtiv Mecarbil and Ivabradine. The primary conclusion drawn from the findings is that Omecamtiv Mecarbil poses potential dangers due to excessive cardiac energy consumption and impaired diastole. The studies conducted, particularly the work by Rødland et al. (2019) in pigs with ischemic acute heart failure, highlight that the combined therapy of Dobutamine and Omecamtiv Mecarbil can be attributed to the effects of Dobutamine rather than a positive impact of Omecamtiv Mecarbil.

Additionally, Rønning et al. (2018) demonstrate opposite diastolic effects of Omecamtiv Mecarbil compared to Dobutamine and Ivabradine co-treatment in pigs with acute ischemic heart failure. This emphasizes the unfavorable diastolic consequences associated with Omecamtiv Mecarbil. The study by Bakkehaug et al. (2015) further supports this by revealing that the myosin activator Omecamtiv Mecarbil increases myocardial oxygen consumption and impairs contractile efficiency, mediated by resting myosin ATPase activity.

In contrast, the research on Ivabradine suggests potential benefits. Bakkehaug et al. (2015) demonstrate that Ivabradine, when co-treated with Dobutamine in acute heart failure, prolongs the diastolic time interval, thereby increasing stroke volume without compromising cardiac efficiency. This implies that Ivabradine may stimulate contractility through adrenergic stimuli while avoiding undesirable tachycardia, presenting a potentially advantageous alternative in the management of acute heart failure.

Furthermore, Bakkehaug et al. (2016) showcase the potential of Ivabradine in reversing Dobutamine-induced tachycardia, leading to increased stroke volume with a neutral effect on cardiac energetics in left ventricular post-ischemia dysfunction. This highlights the versatility of Ivabradine in mitigating adverse effects induced by other treatments.

In summary, the key findings underscore the potential dangers of Omecamtiv Mecarbil, indicating excessive cardiac energy consumption and impaired diastole. On the other hand, Ivabradine emerges as a promising option, offering the potential to stimulate contractility while avoiding detrimental effects on heart function. These insights contribute valuable information to the ongoing exploration of novel inotropic treatments for acute heart failure.

Rødland, L., Rønning, L., Kildal, A. B., Myrmel, T., & How, O.-J. (2019). Combined Therapy With Dobutamine and Omecamtiv Mecarbil in Pigs With Ischemic Acute Heart Failure Is Attributed to the Effect of Dobutamine. Journal of Cardiovascular Pharmacology and Therapeutics, 1074248419881996. https://doi.org/10.1177/1074248419881996

Rønning, L., Bakkehaug, J. P., Rødland, L., Kildal, A. B., Myrmel, T., & How, O.-J. (2018). Opposite diastolic effects of omecamtiv mecarbil versus dobutamine and ivabradine co-treatment in pigs with acute ischemic heart failure. Physiological Reports, 6(19), e13879. https://doi.org/10.14814/phy2.13879

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 postischaemia dysfunction. Acta Physiologica (Oxford, England). https://doi.org/10.1111/apha.12704

Bakkehaug, J. petter, Kildal, A. B., Engstad, E. T., Næsheim, T., Rønning, L., Aasum, E., … How, O.-J. (2015). The myosin-activator Omecamtiv mecarbil increases myocardial oxygen consumption and impairs contractile efficiency mediated by resting myosin ATP ase activity. Circulation: Heart Failure. 2015;8:766–775 https://doi.org/10.1161/CIRCHEARTFAILURE.114.002152

Bakkehaug, J. P., Kildal, A. B., Engstad, E. T., Boardman, N., Næsheim, T., Rønning, L., … How, O.-J. (2015). Response to Letter Regarding Article, “Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity”. Circulation. Heart Failure, 8(6), 1142. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002548