Novel Pharmacological Approaches to Myocardial Thickening: A Randomized Controlled Trial of Trientine

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Summary of  European Heart Journal https://doi.org/10.1093/eurheartj/ehag512 
Dr. John P Farrant  et al.

Points

Researchers at the University of Manchester led the TEMPEST trial evaluating trientine as a novel treatment for hypertrophic cardiomyopathy, an inherited heart condition affecting 1 in 500 people globally.
Results from the 154-patient placebo-controlled trial published in the European Heart Journal demonstrated that one year of trientine therapy significantly reduced left ventricular mass indexed to body surface area.
Clinical subgroup analysis indicated that therapeutic reductions in heart muscle thickening were greatest among participants who presented with more severe hypertrophy at the start of the trial.
Pharmacological action of trientine involves regulating cellular copper levels to restore heart muscle energy production, diminish oxidative cell stress, and prevent progressive myocardial scar tissue formation.
Investigators emphasized that larger clinical studies are required to confirm whether trientine improves functional capacity, symptom burden, and long-term quality of life for hypertrophic cardiomyopathy patients.

Summary

This study evaluated the therapeutic efficacy and safety of trientine, a copper-chelating agent, in mitigating left ventricular hypertrophy in patients with hypertrophic cardiomyopathy (HCM). HCM is the most common inherited cardiac condition globally, affecting approximately 1 in 500 individuals, and is characterized by pathological myocardial thickening and fibrosis. Given that intracellular copper depletion impairs mitochondrial energy production while extracellular unbound copper promotes oxidative stress and scar formation, the trial sought to determine whether modulating copper metabolism via trientine could reverse structural myocardial remodeling.

The double-blind, placebo-controlled TEMPEST trial enrolled 154 adult patients with HCM across a 1-year intervention period. Results demonstrated that trientine administration achieved a statistically significant reduction in left ventricular mass indexed to body surface area compared to placebo. Subgroup analysis revealed that therapeutic regression of myocardial thickening was most pronounced in patients presenting with higher baseline left ventricular mass. The drug was well-tolerated throughout the study, exhibiting a favorable safety profile with few reported adverse events.

These findings suggest that copper modulation via trientine represents a novel therapeutic pathway for reducing myocardial hypertrophy and fibrosis in HCM. While trientine demonstrates significant structural regression in advanced disease, larger phase III trials are necessary to confirm functional symptom improvement and long-term clinical outcomes. Pre-treatment evaluation of structural disease severity may help identify candidates most likely to achieve substantial reverse remodeling.

Link to the article: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehag512/8734889?login=false

References

Farrant, J. P., Dodd, S., Rosala-Hallas, A., Vaughan, C., Spowart, C., Bedson, E., Clayton, D., Reid, A. B., Garratt, C. J., Raman, B., Mahmod, M., Akhtar, M., Valkovič, L., Ashkir, Z., Cooper, R., Singh, A., Prasad, S., Green, T., Dawson, D., … Miller, C. A. (2026). Trientine for hypertrophic cardiomyopathy: A phase 2 trial. European Heart Journal, ehag512. https://doi.org/10.1093/eurheartj/ehag512