International Journal of Scientific Research and Engineering Development

Myocardial energy metabolism plays a critical role in the pathophysiology of ischemic heart disease and chronic heart failure, where impaired substrate utilization and mitochondrial dysfunction lead to reduced adenosine triphosphate (ATP) production and diminished cardiac efficiency. Under pathological conditions, persistent reliance on oxygen-intensive fatty acid oxidation suppresses glucose oxidation, resulting in metabolic uncoupling, intracellular acidosis, and contractile dysfunction. Partial fatty acid oxidation (pFOX) inhibitors have emerged as a novel class of metabolic modulators that improve myocardial energetics by shifting substrate utilization toward more oxygen-efficient glucose oxidation. This review discusses the biochemical basis of myocardial metabolism, mechanisms of metabolic remodelling, and the therapeutic rationale for pFOX inhibition. Key agents including ranolazine, trimetazidine, etomoxir, perhexiline, meldonium, and oxfenicine are evaluated for their mechanisms of action and pharmacological profiles. Available evidence indicates that these agents improve exercise tolerance, reduce anginal symptoms, and enhance ventricular function without significant hemodynamic effects. Additionally, pFOX inhibitors demonstrate potential benefits in heart failure and other metabolic conditions. Despite promising outcomes, limitations related to safety and long-term efficacy warrant further investigation. Overall, pFOX inhibitors represent a promising strategy for improving myocardial efficiency through targeted metabolic modulation

Shifa Bilal Tamboli, Simeen Phiroj Mulani, Arman Tajuddin Shiakh,"Partial Fatty Acid Oxidation (pFOX) Inhibitors: A Metabolic Modulation Strategy in Cardiovascular Disease" International Journal of Scientific Research and Engineering Development, V9(2): Page(2420-2431) Mar-Apr 2026. ISSN: 2581-7175. www.ijsred.com. Published by Scientific and Academic Research Publishing.