Inotropic Therapy in Heart Failure Management

Inotropic therapy remains a cornerstone in the management of heart failure, targeting the fundamental deficit of impaired myocardial contractility. Traditional positive inotropes act by increasing intracellular calcium availability or enhancing myofilament sensitivity, thereby augmenting stroke volume and cardiac output. Common agents include adrenergic agonists such as dobutamine and dopamine, and phosphodiesterase inhibitors such as milrinone. While these drugs can rapidly stabilise patients with acute decompensated heart failure or serve as a bridge to advanced therapies, their use is limited by increased myocardial oxygen consumption, pro-arrhythmic potential and uncertain long-term survival benefit. Recent pharmacological advances have introduced selective sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) activators and myotropes, which enhance contractile performance by restoring calcium cycling or sensitising the contractile apparatus without the energetic penalties of traditional calcitropes. Novel dual-action compounds that combine Na⁺/K⁺-ATPase inhibition with SERCA2a stimulation have shown promise in preclinical models, offering improved diastolic function and reduced adverse effects. Contemporary clinical practice requires careful patient selection, balancing the immediate haemodynamic gains of inotropes against their risks, and integrating these agents into multidisciplinary care pathways that include device therapy, revascularisation and heart transplantation.

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Inotropic Therapy in Heart Failure Management publication trend

The graph below shows the total number of articles in inotropic therapy in heart failure management across all publications each year (not limited to Nature Index journals).

Technical terms

Inotrope: An agent that increases myocardial contractility by modulating calcium handling or myofilament sensitivity.

Lusitropy: The process of myocardial relaxation, often enhanced by agents that accelerate calcium reuptake.

SERCA2a: Sarcoplasmic reticulum Ca²⁺-ATPase isoform 2a, a pump that sequesters calcium into the sarcoplasmic reticulum to facilitate relaxation and subsequent contraction.

Ejection fraction: The percentage of blood ejected from the left ventricle with each heartbeat, a key measure of systolic function.

References

1. Selective SERCA2a activator as a candidate for chronic heart failure therapy. Journal of Translational Medicine (2024).
2. Highly Selective SERCA2a Activators: Preclinical Development of a Congeneric Group of First-in-Class Drug Leads against Heart Failure. Journal of Medicinal Chemistry (2022).
3. A Novel Small Molecule Troponin Activator Increases Cardiac Contractile Function Without Negative Impact on Energetics. Circulation Heart Failure (2021).
4. Efficacy of the New Inotropic Agent Istaroxime in Acute Heart Failure. Journal of Clinical Medicine (2022).
5. Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial functional effects in healthy and diseased human myocardium. Oncotarget (2017).
6. Inotropic Agents: Are We Still in the Middle of Nowhere?. Journal of Clinical Medicine (2024).