In This Series:

• Cardio-Oncology Viewpoint: See Drs. Cheng and Barac's Expert Opinion
• Geriatric Viewpoint: See Dr. Reuben's Expert Opinion
• Palliative Care Viewpoint: See Drs. Warraich and Kirkpatrick's Expert Opinion
• Patient Case(s): See Drs. Vetrovec, Jhatakia, Krishnaswami Patient Case

For both these cases, a cardio-oncology consult will offer a holistic approach integrating potential causative mechanisms with acute management care and longer-term planning in collaboration with interventional cardiology, oncology, palliative care, and geriatrics.

Case #1:
From an etiology standpoint, the question in each case is whether the presentation is due to cardiotoxicity from cancer treatment or coronary artery disease (CAD) unrelated to prior cancer therapy. In the first case, the patient has a history of lung cancer with last chemotherapy and radiation 1.5 years ago. Although the exact regimen was not specified, conventional chemotherapy used in lung cancer treatment is unlikely related to angina based on the mechanisms and timing of last exposure.¹ If the radiation therapy was left-sided, there is certainly concern for cardiotoxicity from radiation. The mean heart dose was not specified, however, delayed onset CAD related to radiation therapy might have played a role in plaque rupture. Although the incidence of ischemic events increases significantly much later, as most cases present at 5 years or later post-radiation exposure,² it is plausible that exposure to therapeutic radiation might have increased the risk for a coronary event. Common risk factors for lung cancer and cardiovascular disease, most importantly, smoking, also need to be considered as a possible culprit. Presence of shortness of breath should alert the team to assess cardiac and pulmonary function in the setting of acute care. Cancer progression, whether in the form of local recurrence, lymph node/mediastinal metastasis or complications such as pleural effusion should be considered but should not preclude active assessment of coronary ischemia.

As a general principle, in cancer survivors who are considered in remission, treatment of angina should follow common acute coronary syndrome (ACS) treatment standards. In addition to medical management, cardiac catheterization is likely to be needed and history of cancer should not preclude or delay indicated diagnostic or interventional procedures. Similarly, decision on percutaneous coronary intervention for culprit lesion will follow standard ACS treatment recommendations.³ If she is found to have ischemic coronary disease and/or cardiomyopathy, the discussion of optimal revascularization approach needs to include oncology assurance that there has been no evidence of cancer progression or need for new cancer treatment.

This patient, within 1.5 years of the last lung cancer treatment, is likely to have received active surveillance and discussion with the oncology team to facilitate decision making, in particular if coronary artery bypass surgery is considered. Prior chest radiation increases this patient's surgical risk as well as the overall risk of subsequent ischemic events, thus making aggressive secondary cardiovascular (CV) prevention strategies a priority.⁴ At the same time, a new diagnosis of ACS may affect her ability to participate in oncology therapeutic trials if she were to progress and need cancer treatment. In summary, this patient should be viewed as a high CV and high oncology risk patient likely to benefit from multidisciplinary discussion and co-management.

Case #2:
Similar to the first case, the immediate diagnostic concern is whether the presenting symptoms may be related to the underlying cancer treatment. The patient in case #2 is actively receiving treatment with pembrolizumab, an antibody from the immune checkpoint inhibitor (ICI) class. In this patient with history of CAD but no typical anginal symptoms, troponin elevation may result from coronary ischemia or autoimmune myocarditis. As a class, ICIs operate by activating hosts T-cells and their antitumor effects, and their immune-related adverse effects (irAEs) differ dramatically from the ones seen with conventional chemotherapies. Although rare and occurring in less than 1% of all patients treated in ICI clinical trials, ICI-related myocarditis needs to be considered as a differential diagnosis as the reported cases of autoimmune myocarditis demonstrate a rapidly progressive course and high mortality.

The clinical presentation of ICI-induced myocarditis has been associated with significant arrhythmias, conduction abnormalities, as well as cardiogenic shock requiring hemodynamic support.^5,6

The treatment of irAEs include high doses of corticosteroids which should be given until diagnosis of myocarditis is excluded. In patients who are hemodynamically stable, cardiac magnetic resonance imaging can be helpful in diagnosing myocarditis although data on its sensitivity and specificity in this clinical entity remain limited. Depending on the patient's clinical status and overall oncology prognosis, coronary angiogram and endomyocardial biopsy should be considered to establish the diagnosis and also aid prognosis. Therefore, the discussion with the oncology team would include the patient's response to immunotherapy, prognosis and available therapeutic options, and understanding that prognosis may be dependent on continued administration of ICIs. In those circumstances, exclusion of autoimmune myocarditis is critical as it would guide therapy and allow ongoing cancer treatment.

If ICI-mediated myocarditis is excluded, and diagnosis of non-ST-elevation myocardial infarction (NSTEMI) is established, acute and chronic management of NSTEMI are likely to be impacted by the active cancer treatment and prognosis.³ The multidisciplinary team therefore should include oncology and palliative care teams in addition to cardiologists.

References

1. Han X, Zhou Y and Liu W. Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy. NPJ Precis Oncol 2017;1:31.
2. Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013;368:987-98.
3. Iliescu CA, Grines CL, Herrmann J, et al. SCAI Expert consensus statement: evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (endorsed by the Cardiological Society of India, and Sociedad Latinoamericana de Cardiologia Intervencionista). Catheter Cardiovasc Interv 2016;87:E202-23.
4. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2017;35:893-911.
5. Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018;71:1755-64.
6. Bonaca MP, Olenchock BA, Salem JE, et al. Myocarditis in the setting of cancer therapeutics: proposed case definitions for emerging clinical syndromes in cardio-oncology. Circulation 2019;140:80-91.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Cardio-Oncology, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Cardiac Surgery and SIHD, Interventions and ACS

Keywords: Acute Coronary Syndrome, Percutaneous Coronary Intervention, Angina Pectoris, Coronary Artery Bypass, Heart Diseases, Patient Care Planning, Patient Care, Terminal Care, Geriatrics, Cardiotoxicity, Cardio-oncology

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