A case of PD-1 inhibitor-induced myasthenia gravis and acute coronary syndrome: a case report

Technical Summary: PD-1 Inhibitor-Induced Myasthenia Gravis and Acute Coronary Syndrome

Problem Statement
Immune checkpoint inhibitors (ICIs), particularly PD-1 inhibitors, have become standard treatments for advanced hepatocellular carcinoma (HCC). While effective, they frequently cause immune-related adverse events (irAEs). Although dermatological, endocrine, and gastrointestinal irAEs are common, neurological and cardiovascular irAEs are less frequent but carry high mortality rates. Specifically, the concurrent occurrence of PD-1 inhibitor-induced myasthenia gravis (MG) and acute coronary syndrome (ACS) is a rare and clinically challenging presentation. Furthermore, the long-term cardiac prognosis for patients surviving ICI-associated ACS, particularly those with persistent biomarker abnormalities, remains poorly understood.

Methodology
This study presents a single-case report of a 65-year-old male with HCC who developed concurrent MG and ACS following treatment with tislelizumab (a PD-1 inhibitor) and lenvatinib. The methodology involved:

• Clinical Monitoring: Detailed tracking of neurological symptoms (ptosis, diplopia, limb weakness, respiratory failure) and cardiac biomarkers (hs-TnT, CK, CK-MB, BNP) and ECG changes.
• Diagnostic Procedures: Utilization of repetitive nerve stimulation (RNS), electromyography (EMG), anti-acetylcholine receptor (AChR) antibody titers, chest CT, echocardiography, and coronary angiography.
• Therapeutic Intervention: Management included immunosuppressive therapy (intravenous immunoglobulin, high-dose methylprednisolone, plasma exchange), cholinesterase inhibitors (Mestinon), and standard ACS management (antiplatelets, anticoagulants, percutaneous coronary intervention).
• Longitudinal Follow-up: The patient was monitored for over 21 months post-discharge, including surveillance imaging for HCC recurrence and serial cardiac evaluations.

Key Results

• Initial Presentation: Thirteen days after the first dose of tislelizumab, the patient developed Osserman Type III MG (positive RNS, anti-AChR antibodies >20 nmol/L) and NSTEMI (elevated hs-TnT, ST-segment depression).
• Treatment Response: Neurological symptoms improved significantly with immunosuppression (IVIG, steroids, plasma exchange), reducing the Quantitative Myasthenia Gravis Score (QMGS) from 19 to 8 points after the acute phase. However, cardiac biomarkers behaved differently; hs-TnT levels remained persistently elevated for more than eight months despite the resolution of neurological symptoms. At discharge (~1.5 months post-event), the level was 0.148 ng/mL, and it spiked to 0.557 µg/L seven months later prior to the second major cardiac event.
• Cardiac Events:
  • Event 1 (Initial): NSTEMI diagnosed during the acute MG phase.
  • Event 2 (7 months post-discharge): The patient suffered an acute ST-segment elevation myocardial infarction (STEMI) with 100% occlusion of the left anterior descending (LAD) artery, requiring stenting.
  • Event 3 (21 months post-discharge): The patient presented with chest tightness and 80–85% stenosis in the right coronary artery (RCA), requiring a second stent.
• Biomarker Trajectory: Unlike conventional ACS where hs-TnT normalizes within 10–14 days, this patient's hs-TnT remained mildly elevated for more than eight months following the initial event and spiked again prior to subsequent major adverse cardiac events (MACE).

Key Contributions

• Documentation of Rare Co-occurrence: The report details a rare case of concurrent PD-1 inhibitor-induced MG and ACS, highlighting the complexity of managing overlapping neurological and cardiovascular irAEs.
• Identification of a Distinct Biomarker Pattern: The authors identify "delayed and persistent hs-TnT elevation" as a potential distinctive feature of PD-1 inhibitor-associated ACS. This contrasts with the typical rapid normalization seen in plaque-rupture-mediated ACS.
• Long-term Risk Stratification: The case demonstrates that persistently elevated hs-TnT in ICI-associated ACS survivors may not merely indicate residual injury but could signal ongoing vascular inflammation or unstable plaques, serving as a predictor for future MACE.

Significance and Claims
The paper claims that this case delivers a critical clinical alert regarding the management of patients with PD-1 inhibitor-induced MG and ACS. The authors assert that:

1. Persistent Biomarkers Signal Risk: Persistently elevated hs-TnT following the resolution of neurological symptoms may indicate ongoing coronary pathology and a high risk of future major adverse cardiac events.
2. Need for Long-term Surveillance: There is an imperative for dedicated, long-term cardiac surveillance in this specific population, extending beyond the acute phase.
3. Mechanistic Insight: The delayed and persistent troponin elevation suggests a pathogenesis distinct from classic plaque rupture, possibly involving prolonged plaque erosion, microthrombus formation, or ICI-associated coronary vasospasm.

The study concludes that while early recognition and management of irAEs are essential, the specific trajectory of cardiac biomarkers in these patients warrants close monitoring to prevent recurrent, severe cardiac events. At the latest follow-up (June 2025), the patient's condition was stable with a QMGS of 1 point.