Atypical Presentation of Myocarditis: Underrecognized Complication of Immune Checkpoint Inhibitors (QF_SA_125)

Saturday, February 1, 2025

8:40 AM – 8:50 AM East Coast USA Time

Location: Blue Room PreFunction

Presenting Author(s)

LB

Luke Beauchamp, BSc, MPH

Medical Student
Michigan State University College of Human Medicine

Co-Author(s)

NM

Nicholas Merritt, N/A

Undergraduate Student
University of Michigan
MD

Mark DeLano, MD

Chairman
Michigan State University

Primary Author(s)

LM

Leena Mammen, MD

Attending Radiologist
Munson Medical Center and Grand Traverse Radiologists

Description of Clinical Presentation: We present a case of Immune Checkpoint Inhibitor (ICI) myocarditis in an 85-year-old male receiving PD-1 inhibitor Keytruda infusions at 3-week intervals for stage 3+ unresectable shoulder melanoma. He presented 8 months after Keytruda initiation with atrial flutter, no chest pain, and elevated high-sensitivity troponin at 141. Echocardiogram showed normal left ventricular function. Cardiac MR (CMR) showed patchy mid-myocardial and extensive septal enhancement with subendocardial sparing (image 1), consistent with myocarditis. LVEF was 48% with no regional wall motion abnormalities. Keytruda was held, and at 3-week follow-up high-sensitivity troponin was 21 and atrial flutter had subsided.

Diagnostic Techniques and Their Most Important Findings:
Myocarditis is reported as a rare ICI therapy complication, associated with high mortality1. Literature estimates myocarditis incidence from 0.06% to 1% among patients on ICIs2. It reportedly often occurs early in therapy. There may be a fulminant course, resulting in cardiovascular collapse and death2. ICI Immune dysregulation can cause immune-related adverse events, with ICI-related inflammation via CD4+ T cells thought to cause cardiomyocyte toxicity and necrosis3,4. Early monitoring uses clinical signs, echocardiography, EKG, and serial lab tests. The most prevalent echocardiography finding is reduced left ventricular longitudinal strain3. ICI myocarditis may present with normal Echo as in this patient2.
CMR has been established as the most important noninvasive imaging modality for evaluating myocarditis, with typical findings of focal or diffuse myocardial edema and myocardial damage, including presence of late gadolinium enhancement (LGE)5. LGE occurs due to increased interstitial space and later with fibrosis of the myocardium. Endocardium is typically spared as in this patient4. Viral and ICI myocarditis demonstrate LGE most commonly in the epicardium of the basal lateral/posterolateral wall6. Septal and mid wall LGE is more commonly reported with ICI myocarditis6. LGE on CMR prognosticates greater risk for adverse outcomes in patients with myocarditis overall, with extensive LGE associated with worse outcomes7.

Learning Points from this Case:
Due to immune suppression, ICI myocarditis patients may exhibit milder and/or atypical clinical presentations despite fulminant-appearing pathology. This patient did not have chest pain, a typical symptom of myocarditis. Rather, this patient presented only with a new rhythm abnormality. Echocardiogram can be normal in myocarditis patients, and a myocarditis diagnosis may be dismissed without the aid of CMR, particularly if patients present atypically.
ICI myocarditis can rapidly progress to cardiovascular collapse, thus prompt ICI cessation, often combined with steroid therapy, is paramount2. Although the condition is rare among patients on ICIs, the mortality rate for ICI myocarditis is high. Increased awareness of this potentially lethal ICI complication, and early use of CMR despite atypical clinical presentation, can provide prompt diagnosis of ICI myocarditis to reduce morbidity and mortality.