A copper-handling drug shrank thickened heart muscle in HCM
In short
In a phase 2, multicentre, placebo-controlled trial of 154 adults with hypertrophic cardiomyopathy, trientine dihydrochloride 400 mg twice daily for 52 weeks reduced left ventricular mass index by 4.4 g/m² versus 1.5 g/m² on placebo — a between-group difference of 3.2 g/m² (95% CI -5.6 to -0.8; P = .009). The effect was larger at higher baseline left ventricular mass and was mediated through a reduction in myocardial cellular mass rather than fibrosis. Adverse event rates were similar in both groups.
Hypertrophic cardiomyopathy is thickened heart muscle, and it is one of the most common cardiac reasons a young person gets told to stop training hard. Drugs so far have targeted symptoms and the outflow tract gradient, not the thickened wall itself. This phase 2 trial (TEMPEST) went at the wall.
The 154 adults enrolled had left ventricular wall thickness of 15 mm or more and NYHA class I to III. Mean age was 53.4, median maximum wall thickness 20.0 mm, and 61.7% were NYHA class I — largely asymptomatic. They received trientine 400 mg twice daily for 52 weeks or placebo, with change in body-surface-indexed left ventricular mass on cardiac MRI as the primary endpoint.
How much did it shrink?
-4.4 ± 7.7 g/m² on trientine against -1.5 ± 6.1 g/m² on placebo, a between-group difference of -3.2 g/m² (95% CI -5.6 to -0.8; P = .009). And the effect grew with baseline left ventricular mass (interaction P = .015) — the thicker the starting heart, the more came off in 52 weeks.
What was lost matters more than how much
Mediation analysis put the reduction squarely in myocardial cellular mass (average causal mediated effect -3.9 g/m²; 95% CI -6.8 to -0.9). The number did not just move; the thickened muscle itself did. On why identical mass figures can mean different tissue, see more left ventricular mass does not mean bigger heart cells.
Why copper?
Depletion of copper I ions in cardiomyocytes impairs mitochondrial function, a state associated with left ventricular hypertrophy. Unbound or loosely bound copper II ions activate profibrotic pathways. Trientine improves intracellular copper I trafficking and availability while chelating copper II. It is not a drug that adds or removes copper — it changes which form sits where.
None of this is an argument for copper supplements. Trientine is a prescription chelator and the trial enrolled people with hypertrophic cardiomyopathy. There is nothing here suggesting a healthy person improves cardiac mass by taking more copper.
Does anything change in the gym today?
No. This is phase 2, and the primary endpoint is an imaging measure, not symptoms or death. Whether 3.2 g/m² of mass translates into less heart failure or fewer arrhythmias is a phase 3 question. What is new is that for people whose training is restricted by an HCM diagnosis, a drug aimed at the wall itself beat placebo for the first time. On training with the diagnosis, see exercise in hypertrophic cardiomyopathy.
Frequently asked questions
What did trientine reduce in hypertrophic cardiomyopathy?
After 52 weeks it lowered body-surface-indexed left ventricular mass 3.2 g/m² more than placebo (95% CI -5.6 to -0.8; P = .009): -4.4 g/m² on trientine against -1.5 g/m² on placebo. The reduction was mediated through myocardial cellular mass rather than fibrosis.
Will copper supplements shrink a thickened heart?
No. Trientine is a prescription agent that improves intracellular copper I trafficking while chelating unbound copper II — the opposite direction from a supplement that simply adds copper. The trial gives no support for increasing copper intake in healthy people.
Who was enrolled in the trial?
154 adults with hypertrophic cardiomyopathy, left ventricular wall thickness of at least 15 mm, and NYHA class I to III. Mean age was 53.4 years, median maximum wall thickness 20.0 mm, and 61.7% were NYHA class I.
Did the drug work better for some patients?
Yes. Efficacy increased with higher baseline left ventricular mass index (interaction P = .015). Patients who started with a thicker heart lost more mass over the 52 weeks.
Was it safe?
Adverse event incidence was similar between the trientine and placebo groups. This was a phase 2 trial over 52 weeks, so long-term safety and any reduction in clinical events remain unconfirmed.
Source: PubMed