Sick sinus syndrome associated with anti-programmed cell death-1

Chien Yi Hsu, Yu Wen Su, San Chi Chen

Research output: Contribution to journalArticle

Abstract

Background: Use of anti-programmed cell death-1 (anti-PD-1) has been successful in treating many types of cancers. Despite its promising efficacy, immune-related adverse events are still a major concern. Immune-related cardiotoxicity, which is rare but fatal, has recently become a focus of attention. Cardiotoxicities including myocarditis, cardiomyopathy, cardiac fibrosis, heart block and cardiac arrest have been reported. Of these toxicities, myocarditis is often accompanied by dysrhythmia. The presentation of sick sinus syndrome as an immune-related adverse event has not yet been reported. Here, we reported the first case of sick sinus syndrome, a rare toxicity induced by anti-PD-1. Case presentation: A 42-year-old male patient who had metastatic hepatocellular carcinoma failed treatment with sorafenib. Pembrolizumab at a fixed dose of 100 mg every three weeks was given. His heart rate gradually slowed down and he presented sick sinus syndrome with a lowest heart rate of 38 bpm after six cycles of pembrolizumab. He denied chest tightness, cold sweating, palpitation and dyspnea. Lab data including cardiac enzyme, electrolytes and thyroid function were all within a normal range. Simultaneously, he complained of fatigue, dizziness and anorexia with hypotension. Lab data revealed low cortisol and ACTH levels. Anti-PD-1 induced adrenal insufficiency was suspected. Low-dose cortisone (12.5 mg) was prescribed, and the patient's symptoms, hypotension and sick sinus syndrome showed rapid improvement. Cortisone was gradually titrated and discontinued three weeks later. His sick sinus syndrome did not relapse and the cortisol and ACTH level returned to normal. Conclusions: Sick sinus syndrome caused by anti-PD-1 treatment is a rare adverse event. With the development of sick sinus syndrome, myocarditis should be the first differential diagnosis because of its lethality. From this case, we learned that sick sinus syndrome may be a presentation of immune- or adrenal insufficiency-mediated sinus node dysfunction, both could be reversed with a glucocorticoid supplement.

Original languageEnglish
Article number72
JournalJournal for ImmunoTherapy of Cancer
Volume6
Issue number1
DOIs
Publication statusPublished - Jul 16 2018

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Sick Sinus Syndrome
Cell Death
Myocarditis
Adrenal Insufficiency
Cortisone
Heart Arrest
Hypotension
Adrenocorticotropic Hormone
Hydrocortisone
Heart Rate
Heart Block
Sweating
Anorexia
Dizziness
Cardiomyopathies
Dyspnea
Electrolytes
Glucocorticoids
Fatigue
Hepatocellular Carcinoma

Keywords

  • Adrenal insufficiency
  • Anti-programmed cell death-1
  • Hepatocellular carcinoma
  • Immune-related adverse event
  • Sick sinus syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Sick sinus syndrome associated with anti-programmed cell death-1. / Hsu, Chien Yi; Su, Yu Wen; Chen, San Chi.

In: Journal for ImmunoTherapy of Cancer, Vol. 6, No. 1, 72, 16.07.2018.

Research output: Contribution to journalArticle

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