Cover Image

Toxicity to immune checkpoint inhibitors presenting as pulmonary arterial vasculopathy and rapidly progressing right ventricular dysfunction

Prakash Sanzgiri, Smruti Koppikar, Krishna BA, Pallavi Patil, Charan Reddy


Introduction: Immune Checkpoint Inhibitors (ICIs) are antitumor drugs associated with a number of serious immune-related adverse events (IRAEs). ICIs enhance anti-tumor immunity, thereby  energized  patient's immune system to fight cancer. IRAEs may affect functions of various organs, including heart, and may lead to morbidity and, to some  extent  mortality. Left ventricle (LV) myocarditis with dysfunction is a known side effect of this class of drugs. However, right ventricle (RV) myocarditis and pulmonary vasculitis are an unknown entity and has not been previously reported.  Here, we present the first case of  IRAEs causing selective RV involvement with dysfunctions, attributed to immune checkpoint inhibitors described till date in medical literature.

Presentation of Case: A 58-year male presented  with history of low-grade fever and  weight loss. On palpation, he had diffuse cervical lymphadenopathy. Histopathology evaluation of  lymph node revealed  metastatic lesions of Renal Cell Carcinoma (RCC).

Conclusion: Fatal cardiovascular adverse events can occur as a side effect of ICI. The combination of RV myocarditis with progressive pulmonary hypertension is fatal. Treatment with high dose corticosteroids and immunomodulators may help in patient survival. Physicians treating patients with ICIs should be aware of their lethal cardiotoxic side effects  to reduce adverse cardiac outcomes. Because the number of patients exposed to this new immune therapy is expected to increase remarkably in the near future, our study encourages further work to define guidelines for cardiovascular monitoring and management.


Immune checkpoint inhibitors; myocarditis; pulmonary vasculitis; renal cell carcinoma


Kabir TF, Chauhan A, Anthony L, Hildebrandt GC. Ochsner J. 2018, 18:370-376

Alatrash G, Daver N, Mittendorf EA. Targeting Immune Checkpoints in Hematologic Malignancies. Pharmacol Rev. 2016, 68:1014-1025

Young COK, Young KH. Checkpoint inhibitors in hematological malignancies. J Hematol Oncol. 2017, 10: 103

Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013, 369:122-133

Carter T, Shaw H, Cohn-Brown D, et al. Ipilimumab and bevacizumab in glioblastoma. Clin Oncol (R Coll Radiol). 2016, 28:622-626

Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011, 364:2517-2526

Park JA, Cheung NV. Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies. Cancer Treat Rev. 2017, 58: 22-33

Varricchi G, Marone G, Mercurio V et al. Immune checkpoint inhibitors and cardiac toxicity: an emerging issue. Curr Med Chem. 2018, 25:1327-1339

Cuomo A, Rodolico A, Galdieri A, Russo M, Campi G, et al. Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients. Card Fail Rev. 2019, 5: 112-118

Lyon AR, Yousaf N, Battisti NM, Moslehi J, Larkin J. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018, 19:e447-e458

Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016, 375:1749-1755

[Heinzerling L, Ott PA, Hodi FS, et al. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J ImmunoTherapy Cancer. 2016, 4:50

Escudier M, Cautela J, Malissen N, et al. Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation. 2017, 136: 2085-2087

Costa F, Das R, Bailur JK, et al. Checkpoint Inhibition in Myeloma: Opportunities and Challenges. Front Immunol. 2018, 9:2204

Salem JE, Manouchehri A, Moey M, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. The Lancet Oncology• 2018, 19:1579-1589

Tajiri K, Ieda M. Cardiac Complications in Immune Checkpoint Inhibition Therapy. Front Cardiovasc Med. 2019, 6:3

Hu J, Florido R, Lipson EJ, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors . Cardiovascular Research. 2019, 115:854-868

Maawy AA, Ito F. Future of immune checkpoint inhibitors. In: Ito F, Ernstoff M, (eds). immune checkpoint inhibitors in Cancer. Elsevier, Inc; St. Louis, MO: 2019, pp. 227-243

Upadhrasta S, Elias H, Patel K, Zheng L. Managing cardiotoxicity associated with immune checkpoint inhibitors. Chronic Dis Transl Med. 2019, 5:6-14

Baldetti L, Melillo F, Beneduce A, Camici PG. Combined checkpoint inhibitor-associated myocarditis and pulmonary vasculitis mimicking acute pulmonary embolism. Eur Heart J Cardiovasc Imaging. 2019, 20:243

Mancio J, Bettencourt N, Oliveira M, et al. Acute right ventricular myocarditis presenting with chest pain and syncope. BMJ Case Rep. 2013, bcr2012007173

Virk HU, Munir MB. Isolated Right Ventricular Myocarditis: Rarely Reported Pathology. Case Rep Cardiol. 2015, 790246

Full Text: PDF


  • There are currently no refbacks.

AJCC-REP (ISSN 2572-5742)Copyright © 2012-2019. All rights reserved. Published by Ivy Union Publishing, 3204 Valley Rush Dr, Apex, North Carolina 27502, United States