Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation

J Immunother. 2021 Jun 1;44(5):179-184. doi: 10.1097/CJI.0000000000000371.

Abstract

The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value <53%. Fifty-two patients were included with a male preponderance (65%) and a mean age of 66 (±12) years. Twelve (23%) patients developed CTRCD, of which 2 patients were diagnosed with myocarditis. Among the CTRCD group, patients tended to be older and more likely to have baseline diastolic dysfunction: lower e' septal (P=0.026), higher E/e' septal (P=0.035), and a trend of E/e' average (P=0.076). All-cause and cardiovascular hospitalizations were significantly more common among the CTRCD group (P=0.028 and 0.001, respectively). Higher prevalence of cardiovascular mortality was observed among the CTRCD group (25% vs. 2%, P=0.034). We evaluated the development of CTRCD among patients treated with ICI therapies. Our findings suggest that baseline diastolic parameters may be associated with CTRCD development assisting in the early diagnosis of ICI-induced cardiac injury.

MeSH terms

  • Aged
  • Cardiotoxicity / diagnosis*
  • Cardiotoxicity / epidemiology
  • Cardiotoxicity / etiology*
  • Comorbidity
  • Disease Susceptibility
  • Echocardiography
  • Electrocardiography
  • Female
  • Heart Diseases / diagnosis*
  • Heart Diseases / epidemiology
  • Heart Diseases / etiology*
  • Heart Function Tests
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Outcome Assessment, Health Care
  • Risk Factors

Substances

  • Immune Checkpoint Inhibitors