Role of Trientine in Hypertrophic Cardiomyopathy: A Review of Mechanistic Aspects

Abstract

Abnormality in myocardial copper homeostasis is believed to contribute to the development of cardiomyopathy. Trientine, a copper-chelating drug used in the management of patients with Wilson’s disease, demonstrates beneficial effects in patients with hypertrophic cardiomyopathy. This review aims to present the updated development of the roles of trientine in hypertrophic cardiomyopathy. The drug has been demonstrated in animal studies to restore myocardial intracellular copper content. However, its mechanisms for improving the medical condition remain unclear. Thus, comprehending its mechanistic aspects in cardiomyopathy is crucial and could help to expedite future research.

Clinical Trials in Hypertrophic Cardiomyopathy Therapy: A Comprehensive Analysis of Trials Registered in Global Clinical Databases

“… NCT05174416 Recruiting Phase 3 Valsalva LVOT peak gradient NCT05582395 Not yet recruiting Phase 3 KCCQ-23 CSS and pVO2 Trientine NCT04706429 Authorized Phase 2 Left ventricular mass indexed to body surface area Unapproved for HCM; Approved for adult patients with stable Wilson’s disease Glypican-1 Chelating Agent Discerning Copper(II) Chelator; Ameliorates LVH by reducing hypertrophy and fibrosis, improving mitochondrial function and energy metabolism. 40 Aficamten NCT04219826 Active, not recruiting Phase 2 Incidence of AEs Unapproved for HCM *Myosin 41 Myosin Inhibitors Exhibits specific and reversible binding to myosin; Diminishes actin-myosin cross-bridge interactions and decreasing Contractility; Brings About Reductions In LVOT Gradients. 42 NCT05186818 Recruiting Phase 3 pVO2 Empagliflozin NCT05182658 Not yet recruiting Phase 3 pVO2 Unapproved for HCM; Approved for type 2 diabetes Sodium/Glucose Cotransporter 2 Enzyme Inhibitor Improves Mitochondrial Function; Reduces LVEF; Decreases The Risk Of Worsening HF.…”

“…Ameliorates LVH by reducing hypertrophy and fibrosis, improving mitochondrial function and energy metabolism. 40 …”

Parkia speciosa Hassk. Empty Pod Extract Prevents Cardiomyocyte Hypertrophy by Inhibiting MAPK and Calcineurin-NFATC3 Signaling Pathways

“…Quercetin 3′-glucoside and quercetin 3-(6‴-sinapylglucosyl)(1->2)-galactoside were putatively identified in the ethyl acetate fraction of the present study. Oxidative stress and inflammation play a prominent role in the development of myocardial hypertrophy [ 29 ]. However, the cardioprotective effect of the ethyl acetate fraction was not seen at the highest concentration (200 µg/mL).…”

Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases

“…Trientine was demonstrated to Frontiers in Pharmacology frontiersin.org selectively chelate Cu and improve mitochondrial function in patients with hypertrophic cardiomyopathy (Reid et al, 2022). Additionally, trientine restored mitochondrial structural damage and myocardial metabolic enzyme activity in diabetic patients (Ramli et al, 2022). Metal chelators have several disadvantages, including heavy metal redistribution from other tissues to the brain, which can worsen brain toxicity and result in the loss of essential metals and liver toxicity (Yuan et al, 2017).…”

“…Trientine was demonstrated to selectively chelate Cu and improve mitochondrial function in patients with hypertrophic cardiomyopathy ( Reid et al, 2022 ). Additionally, trientine restored mitochondrial structural damage and myocardial metabolic enzyme activity in diabetic patients ( Ramli et al, 2022 ).…”