Is imatinib (tyrosine kinase inhibitor) used in the treatment of heart failure cardiomyopathy?

Imatinib is Not Recommended for Treatment of Heart Failure Cardiomyopathy

Imatinib (Gleevec), a tyrosine kinase inhibitor, is not recommended for the treatment of heart failure cardiomyopathy and may actually cause cardiotoxicity, particularly in older patients and those with pre-existing cardiac conditions. 1, 2

Cardiotoxic Effects of Imatinib

• Imatinib has been associated with cardiotoxicity through several mechanisms:

  • Mitochondrial abnormalities and accumulation of membrane whorls in vacuoles and sarco(endo)plasmic reticulum 1
  • Activation of endoplasmic reticulum stress response in cardiomyocytes 1
  • Collapse of mitochondrial membrane potential and reduction in cellular ATP content 1
  • Depletion of the transcription factor GATA4 resulting in decreased levels of prosurvival targets Bcl-2 and Bcl-XL 2

• Clinical studies have documented cases of severe congestive heart failure in patients receiving imatinib therapy, with animal models confirming left ventricular contractile dysfunction 1

Risk Factors for Imatinib-Induced Cardiotoxicity

• Age is a significant risk factor for imatinib cardiotoxicity:

  • Older patients are more susceptible to cardiotoxic effects 2
  • Age-dependent increase in oxidative stress contributes to greater cardiotoxicity 2

• Pre-existing cardiac conditions increase risk:

  • Patients with history of congestive heart failure, diabetes mellitus, hypertension, coronary artery disease, arrhythmia, or cardiomyopathy are at higher risk 3
  • In a review of 1276 patients on imatinib, 22 (1.7%) developed symptoms attributable to systolic heart failure, with 18 having pre-existing cardiac conditions 3

Imatinib in Patients with Existing Cardiomyopathy

• Patients with existing cardiomyopathy who require imatinib for conditions like chronic myeloid leukemia (CML) may experience various cardiovascular events 4

• For patients with both CML and severe dilated cardiomyopathy, alternative tyrosine kinase inhibitors with different mechanisms of action may be considered 4

• Imatinib has been shown to induce cardiac progenitor cell depletion, reduced growth, and increased cell death, which may contribute to its cardiotoxic effects 5

Current Guidelines for Heart Failure Management

• Current heart failure guidelines from the European Society of Cardiology (2016) and American College of Cardiology/American Heart Association (2022) do not include imatinib as a recommended therapy for heart failure cardiomyopathy 6

• Standard guideline-directed medical therapy for heart failure includes:

  • ACE inhibitors, ARBs, or ARNI (angiotensin receptor-neprilysin inhibitors) 6
  • Beta-blockers 6
  • Mineralocorticoid receptor antagonists 6
  • SGLT2 inhibitors 6
  • Diuretics for symptom relief 6

• For patients with worsening heart failure, guidelines recommend optimizing evidence-based therapies rather than introducing experimental agents 6

Conclusion

Imatinib is not indicated for the treatment of heart failure cardiomyopathy. On the contrary, it has demonstrated cardiotoxic effects that can lead to or worsen heart failure, particularly in older patients and those with pre-existing cardiac conditions. Patients with heart failure should be treated according to established guidelines with proven therapies that improve morbidity and mortality.