Spectrum of CV Effects of Immune Checkpoint Inhibitors Defined

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Immune checkpoint inhibitors (ICI) are a widely used and effective treatment for many cancers, but their full range of cardiovascular (CV) complications is not well understood.

  • Among the spectrum of CV complications associated with ICI treatment, myocarditis is the most common, but atrial tachyarrhythmias, noninflammatory left ventricular dysfunction (NILVD), and other conditions are also possible.

Why This Matters

  • The study describes real-world experiences in diagnosis and management of a range of cardiac complications in patients with cancer who are receiving ICI therapy.

  • The number of patients presenting with these complications may well increase as the number of licensed indications for ICIs expands, cardiologists and oncologists become more aware of the broad spectrum of cardiac events, and more patients with cancer survive and receive longer courses of ICI treatment.

Study Design

  • In the retrospective analysis, 110 patients out of a total 2647 on ICI therapy were referred to the cardio-oncology service with possible CV complications from 2014 through 2020.

  • Patients were included if they had ICI-treated active cancer at the time of referral and new CV disease without an alternative explanation.

  • Other exclusion criteria included absence of CV complications on assessment by the cardio-oncology service, loss to follow-up before completion of their CV assessment, referral for assessment of preexisting CV disease, and referral to monitor ICI therapy response of an intracardiac metastasis.

  • Among the 89 patients included in the final analysis, 55% were men, and their median age was 63.

Key Results

  • The most common primary cancer was melanoma, seen in 30% of the patients, followed by urinary tract cancer in 23% of patients, and lung cancer in 16%.

  • The anti–programmed cell death protein 1 antibody pembrolizumab was the most frequently prescribed ICI, used in 28 patients; followed by combination therapy with ipilimumab and nivolumab in 24 patients; and single-ICI therapy with nivolumab in 13, durvalumab in 10, and atezolizumab in nine patients.

  • Myocarditis was the most common CV complication, occurring in 33 patients. Of those, 51% had definite myocarditis, 29% probable myocarditis, and 20% possible myocarditis according to published criteria. High-dose steroids were used in 73% of patients.

  • Atrial or ventricular tachyarrhythmias were the most frequent cardiac event and were seen in 30 patients. Of those, 12 were treated with anticoagulation, rate control medication, or ablation as necessary.

  • NILVD in the absence of myocarditis, ischemia, infarction, or other acute causes was observed in 15 patients. Of those, 73% were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and 47% were put on beta-blockers. ICI therapy was safely restarted in 11 patients.

  • Other CV complications included pericarditis in seven patients, ischemic heart disease due to microvascular dysfunction or acute coronary syndrome in six patients, vasovagal syncope in four patients, bradyarrhythmia in four, new pulmonary artery hypertension in two, and cytokine release syndrome in one patient.


  • The single-center observational study had potential for referral bias, and some CV complications may have been not recognized.

  • A matched, untreated control cohort was not available.

  • Some data regarding ICI treatment before development of adverse events are not consistently available.


  • The study was funded by the Royal Brompton Hospital Charity and the Fondation Leducq Network of Excellence in Cardio-Oncology.

  • One author disclosed receiving speaker, advisory board, or consultancy fees and/or research grants from Pfizer, Novartis, Servier, AstraZeneca, Bristol-Myers Squibb, GSK, Amgen, Takeda, Roche, Janssens-Cilag, Ltd, Clinigen Group, Eli Lily, Eisai, Ltd, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health and Heartfelt Technologies, Ltd. The other authors had no disclosures.

This is a summary of a preprint research study, “The Spectrum of Cardiovascular Complications Related to Immune-Checkpoint Inhibitor Treatment,” written by Maria Sol Andres, from the Royal Brompton Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, and colleagues on ResearchSquare.com, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

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