Prednisone administration in inflammatory cardiomyopathy: caveat for potentially adverse myocardial actions

This commentary refers to ‘Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy: 20-year follow-up of the TIMIC trial’, by C. Chimenti et al., https://doi.org/10.1093/eurheartj/ehac348 and the discussion piece ‘Prednisone for inflammatory cardiomyopathy: more than just an immunosuppressive agent’, by Z. Yang et al., https://doi.org/10.1093/eurheartj/ehad068.

We thank Chao Liu and co-authors for contributing in their report ‘Prednisone in inflammatory cardiomyopathy: more than just an immunosuppressive agent’ to clarify the molecular pathway that make prednisone, in addition to its immunosuppressive and anti-inflammatory action, an agent able to improve both renal and cardiac function.

Indeed, recovery of cardiac dilatation and function in those patients with virus-negative inflammatory cardiomyopathy responding to combined prednisone and azathioprine are associated at control biopsy with decrease of myocyte apoptosis and necrosis by 85% and 62% respectively, increase of myofibrillar area by 33% as well as a higher number of new born, Ki67and MCM5 positive, myocytes.¹ The latter cells replace dying cardiomyocytes following HMGB1 signaling that consent their appropriate homing and integration within empty scaffolds of inflammed myocardium. Summarizing major structural changes concur together with enhanced functional pathways to improvement of heart failure.

Furthermore, we have to remind the adverse myocardial actions that may accompany chronic administration of prednisone. They include² activation into cardiomyocytes of Foxo transcription factors, overexpression of atrogin-1 and ubiquitin promoting proteasome proteolysis of endogenous contractile elements and cell apoptosis. On clinical ground the patient may develop a Cushing cardiomyopathy³ characterized by elevation of heart rate, impairment of cardiac contractility and occurrence of electrical instability.

These considerations led us to reduce prednisone administration in our TIMIC protocol applied to inflammatory cardiomyopathy patients from 1 mg/Kg to 0.33 mg/Kg after the first 4 weeks of therapy lasting 6 months.⁴

In conclusion a careful balance between positive and unfavorable effects of prednisone administration has to be considered in its chronic use.

Author contributions

Cristina Chimenti (Conceptualization: Lead; Investigation: Lead), Matteo Antonio Russo (Data curation: Supporting), and Andrea Frustaci, M.D.

Data availability

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Funding

The study has been supported by funding from the Italian Ministry of Health Ricerca Corrente #2020/1 given to IRCCS Spallanzani and IRCCS San Raffaele Roma.

References

Author notes