#apaperaday: Tamoxifen may contribute to preserve cardiac function in Duchenne muscular dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Tamoxifen may contribute to preserve cardiac function in Duchenne muscular dystrophy

A paper on tamoxifen’s potential effect on cardiac function in Duchenne by Henzi et al from European Journal of Pediatrics DOI: 10.1007/s00431-024-05670-9

Duchenne patients have loss of muscle tissue that affects skeletal muscle but also the heart, where muscle tissues are replaced by fibrotic and adipose tissues. In a mouse model for Duchenne, tamoxifen treatment reduced the amount of fibrosis significantly.

However, in a subsequent clinical trial in Duchenne patients, no effect on motor function was seen in ambulant patients on top of steroid treatment. Here, authors wanted to look retrospectively/in a post hoc fashion to see if there was an impact on heart function.

Authors (correctly) point out that this is not a confirmatory analysis, but one to generate a hypothesis (is this something we might want to look into?). As the trial was not designed to study heart pathology and function, only 14 patients were available for this post hoc analysis.

These patients were 7-14 years old, 7 were treated with placebo and 7 with tamoxifen. Baseline ECGs were available for 7 patients, and final timepoints from 9 patients. Note that these ECGs were not taken as part of the trial, but were part of ‘care/management ECGs.’

Authors compare left ventricular end diastolic and systolic volume and fractional shortening in (I assume) the patients where they had baseline and final analyses available. This revealed a small decline in heart function for placebo and a small improvement for tamoxifen.

What does this mean? Authors outline the limitations: for now, this does not mean anything as the numbers were very small, they could not also check heart biomarkers in blood, ECG as done here has a low resolution, and advanced ECG or MRI might have been better.

This is, of course, in hindsight – authors had to work with what was available. Authors discuss that only 1 patient out of 14 was on cardiac treatment, while this is recommended by the standards of care for patients aged 10 and older. This shows more awareness is needed for this.

Authors end by stating that more work is needed (also in the abstract). For now, I refrain from drawing any conclusions as the decline and improvements are both very small, and the differences between the groups are very small, and the groups themselves are very small.