Contents

πŸ“’ Henriksen 2018

Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention1

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Anthracycline-induced cardiotoxicity

  • Anthracyclines (doxorubicin, daunorubicin, epirubicin and idarubicin) : broad-spectrum antineoplastic https://user-images.githubusercontent.com/40054455/86618941-535cd000-bfec-11ea-9a43-fd582efd38e4.png
  • dose-related cardiomyocyte injury => LV dysfunction, HF. Cardiac event rates on treatment were 7%, 18% and 65% at cumulative doses of 150 mg/m2, 350 mg/m2 and 550 mg/m2, respectively

Mechanism of anthracycline cardiotoxicity

https://user-images.githubusercontent.com/40054455/86618936-522ba300-bfec-11ea-8784-cd3c44829c2a.jpg

  • Increased reactive oxygen species (ROS) formation and inhibiting Topoisomerase 2Ξ² in cardiomyocytes, as well as iron accumulation inside mitochondria

Risk markers for anthracycline cardiotoxicity

  • cumulative dose, female sex, African-American ancestry, age >65 years or <18 years, renal failure and concomitant exposure of the heart to radiation therapy
  • concentrations of Top 2Ξ² in peripheral blood leucocytes: low = more resistant to anthracycline cardiotoxicity
  • The hiPSC-CMs from patients who developed LVEF depression exhibited increased cell death and ROS production following in vitro doxorubicin challenge

Monitoring for cardiotoxicity

LVEF and global longitudinal strain

  • LVEF decrease of >10 percentage points from baseline to a value <53% on repeat confirmatory echocardiographic imaging
  • Baseline LV dysfunction is a strong marker for developing heart failure complications with anthracycline

Cardiac biomarkers

  • Cardiac troponin I (cTnI) and cardiac troponin T

Prevention and treatment of cardiotoxicity

Anthracycline derivatives and infusion protocols

  • Reducing the cumulative anthracycline dose
  • Liposomal encapsulation: modifies tissue distribution, but expensive

Dexrazoxane (DRZ)

  • DRZ is taken up rapidly by the myocardium following infusion and competes with ATP-binding sites on Top 2Ξ²
  • Concerns about less effective treatment in children: restricted use in adults with metastatic breast cancer receiving higher cumulative anthracycline dose

Angiotensin inhibition and Ξ²-blockade

  • decline in LVEF => ACEi/ARB and Ξ²-blockers
  • Primary prevention with Ξ²-blockade, ACEi and ARBs? Under studies

Primary prevention with statins

  • More research is needed

Conclusions

  • Anthracycline chemotherapy remains an important and effective treatment for breast cancer, haematological malignancies and sarcoma
  • cardiotoxicity is dose-dependent
  • Testing: LVEF, cTnI
  • Cardioprotective therapies: DRZ, ACEi/ARB and Ξ²-blockers

References


  1. Henriksen PA. Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart 2018;104(12):971-977. doi:10.1136/heartjnl-2017-312103. ↩︎