Immune Checkpoint Inhibitors and Myocardial Injury

Oncological immunotherapies have revolutionized the treatment of patients with cancer in the past decade. Immune checkpoint inhibitor (ICI) utilization continues to increase, significantly improving outcomes for many cancers. This class of antineoplastic therapy does, however, carry cardiovascular complications – most notably acute, potentially fatal autoimmune myocarditis, although the overall prevalence of immune-related myocardial injury is not well understood. In response to this potential complication, several institutions have incorporated surveillance protocols for the early detection of myocardial injury in this population.

At #AHA22, I (VZ) proposed and moderated a session that explored the intersection of immuno-oncological therapies and the cardiovascular system. Several new ideas were discussed regarding ICI-induced myocarditis:

1. Novel data were presented supporting a role for sex differences in myocarditis, demonstrating that female sex hormones increased the risk of ICI-induced myocarditis. This work was led by Drs. Chunru Lin and Liuqing Yang from MD Anderson Cancer Center, in a collaborative project with Dr. Javid Moslehi from UC San Francisco.
2. From a registry of patients with cancer treated with ICI at the University of Michigan, Dr. Salim Hayek reported that patients with autoimmune hepatitis and myositis had an increased prevalence of myocarditis. These data suggest that patients with these comorbid conditions should undergo surveillance for myocarditis when treated with ICI.
3. Dr. Joe-Elie Salem from Sorbonne University discussed novel approaches to treat ICI-induced myocarditis. Specifically, he reported that clinical trials with abatacept, a CTLA-4 fusion protein targeting CD86 on antigen presenting cells that leads to global T-cell anergy, and ruxolitinib, a janus kinase inhibitor, were planned.

In a separate session, one of us (AR) presented data on the prevalence of cardiac injury, as defined by high-sensitivity troponin I (hs-TnI) elevation, in patients undergoing treatment with ICI at UT Southwestern. The universal definition of myocardial infarction was used to identify patients with cardiac injury at baseline and after initiation of ICI therapy. We found a significant association between acute (on ICI therapy) or acute-on-chronic (at baseline with further elevation on ICI therapy) cardiac injury and all-cause mortality in patients undergoing treatment with ICI. These data suggest a role for cardiac-specific biomarker surveillance in this patient population, both to enhance risk-stratification as well as to design preventive or therapeutic strategies.