Cardio-Oncology for the Interventionalist—Part 1 | SCAI

By: Christine Gasperetti, MD, FSCAI, and Jayant Bagai, MD, FSCAI

Cancer has become a disease in evolution with promising and effective therapies in continuous development. With nearly 17 million cancer survivors in the U.S., Cardiologists will diagnose and treat increasing numbers of patients with short- and long-term cardiac effects of cancer and its therapies. To that end, SCAI has published an Expert Consensus Statement for the evaluation and management of Cardio-Oncology patients in the cardiac catheterization laboratory (CCL).1 The most common cardiac events in cancer patients from the perspective of the Invasive/Interventional Cardiologist and the CCL include acute coronary syndrome (ACS) due to coronary thrombosis, unstable angina due to coronary vasospasm, pericardial disease, myocarditis, and Takotsubo cardiomyopathy, which can mimic ST-segment elevation myocardial infarction (STEMI) and/or cause severe cardiogenic shock. The focus in this two-part Tip of the Month will be on coronary complications. Part 1 provides an overview of the cardiovascular, especially coronary, complications of cancer therapy. Part 2 contains tips on management of the cancer patient with ACS and cancer patients who require percutaneous coronary intervention (PCI).

Chemotherapy-Induced Cardiovascular Toxicity

Therapies used to treat cancer can cause ACS, stroke, arrhythmias, heart failure, and critical limb ischemia (see Table 1). A classic example is 5-fluorouracil (5-FU), which is commonly associated with vasospasm and thrombosis (see Figure 1). These presentations may occur in patients with or without known cardiovascular disease (CVD). Immunotherapies for cancer are revolutionizing treatment but carry their own unique risk of cardiac toxicity. An example of this are the so-called immune checkpoint inhibitors (ICI), which are associated with myocarditis and vasculitis.2 The diagnosis of myocarditis can be especially challenging and may resemble ACS with patients presenting with dyspnea, chest pain, elevated troponin, and electrocardiogram (EKG) changes. In all such cases, ACS needs to be ruled out with coronary angiography.

Agent Cardiovascular Toxicity Mechanism
5-fluorouracil (5-FU) and its pro-drug capecitabine Vasospasm, myocardial ischemia, potentially lethal arrhythmias, Takotsubo cardiomyopathy Endothelial damage, alterations in molecular signaling pathways that control vascular smooth muscle tone; can begin immediately after drug initiation
Paclitaxel and less often, docetaxel Bradycardia, myocardial ischemia, and myocardial infarction (MI); unrecognized coronary artery disease (CAD) may be a predisposing factor Vasospasm
Cisplatin Acute coronary thrombosis; may involve multiple vascular territories, twofold to sevenfold increase in long-term risk of CAD and MI Endothelial damage, thromboxane production, platelet activation, and aggregation
Bleomycin and vinblastine (especially in combination with cisplatin) Myocardial ischemia Endothelial dysfunction, apoptosis
Cyclophosphamide Prinzmetal’s angina, hemorrhagic perimyocarditis Endothelial toxicity
Vascular endothelial growth factor inhibitors such as bevacizumab, sunitinib, and sorafenib Twofold to sixfold increase in risk of acute cardiovascular events, decrease in coronary flow reserve, vasospasm (sorafenib), plaque rupture (sunitinib), bleeding, and hypertension Endothelial dysfunction, inflammation, platelet activation, interference with plaque neovascularization, endothelin, and superoxide production
Tyrosine kinase inhibitors: nilotinib and ponatinib Atherosclerosis progression, vasospasm, ischemic events—peripheral more common with nilotinib, coronary more common with ponatinib Augmentation of calcium sensitization, inhibition of calcium ion channels, myocardial cytotoxicity
Bruton’s tyrosine kinase (BTK) inhibitors, especially ibrutinib Hypertension, atrial fibrillation, increased bleeding risk Unknown
Gonadotropin-releasing hormone (GnRH) agonists and aromatase inhibitors Angina, MI Atherosclerosis progression, hypercoagulability
Multiple myeloma therapies, including immunomodulatory drugs (ImiDs), especially lenalidomide, and proteasome inhibitors, especially carfilzomib Venous and arterial vascular events: risk of MI with lenalidomide ~ 2 percent, risk doubles with addition of carfilzomib; most patients on ImiDs should be prescribed prophylactic antiplatelet therapy or anticoagulation Modulation of the protein degradation machinery
Immunotherapies (ICIs-Immune Checkpoint Inhibitors):  nivolumab, pembrolizumab, and atezolizumab Myocarditis (sometimes fulminant), Takotsubo cardiomyopathy, pericarditis, vasculitis; there should be a low threshold for endomyocardial biopsy in cases of myocarditis Activation of the immune system
Anti-CD 20 antibody: rituximab STEMI Cytokine-mediated plaque rupture


Table 1 – Chemotherapeutic agents associated with cardiovascular events. Adapted from reference 1.


Radiation-Induced CVD

Radiation is toxic to endothelial cells, resulting in accelerated atherosclerosis and thrombosis. A high index of suspicion should be present when evaluating a patient who received mediastinal radiation in childhood or adolescence. It takes an average time of seven years to develop radiation-induced CAD. Involvement of the ostial left main and/or right coronary artery is a classic lesion, seen in up to 20 percent of patients, years after chest irradiation for Hodgkin’s lymphoma (HL). Patients who receive radiation for left-sided breast cancer may develop mid-distal left anterior descending (LAD) and distal diagonal lesions or ostial stenosis. Patients may not have traditional risk factors for CAD and may have “negative” stress tests.3 In terms of treatment with PCI, patients with HL have a higher risk of in-hospital death, stroke, and bleeding compared with controls.4 Patients with preexisting cardiac risk factors, who have also received mediastinal radiation and chemotherapeutic agents with vascular toxicity, face a high lifetime risk of cardiovascular events.


Figure 1
Figure 2
Figure 3


Figure 1—65-year-old man with a history of hyperlipidemia, hypertension, known CAD, s/p drug-eluting stent (DES) to LAD, nonsmoker diagnosed with colon cancer and on 9th cycle of chemotherapy. 

Patient developed severe chest pain following home infusion of 5-FU. EKG (top) showed lateral ST elevation. Nitroglycerin completely relieved both pain and ST elevation (middle). Angiogram (bottom) showed a complex bifurcation obtuse marginal (OM) lesion, which was not treated due to a recent gastrointestinal (GI) bleed. Such patients can be cautiously rechallenged with 5-FU after pretreatment with a Ca channel blocker and nitrate. IV nitroglycerin may be needed.


With the advent of more effective drugs, treatment is now commonly provided to older cancer patients who also have CVD. In addition, novel modes of action of cancer therapies, such as immunotherapy, can result in cardiovascular toxicity in patients without known CVD. Interventionalists, therefore, need to be aware of the unique cardiac risk profiles of commonly used classes of cancer drugs and radiation when taking care of a cancer patient in the cath lab. Close collaboration with Oncology/Hematology and Cardio-Oncology is strongly recommended when taking care of cancer patients with cardiac disease. Management of ACS and PCI considerations in cancer patients will be presented in Part 2 next month.


1. 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. Catheter Cardiovasc Interv. 2016 Apr;87(5):E202-23.

2. Salem JE, Manouchehri A, Moey M, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018 Dec;19(12):1579-89.

3. Lee MS, Finch W, Mahmud E. Cardiovascular complications of radiotherapy. Am J Cardiol. 2013 Nov 15;112(10):1688-96.

4. Borovac JA, Kwok CS, Iliescu C, et al. Percutaneous Coronary Intervention and Outcomes in Patients With Lymphoma in the United States (Nationwide Inpatient Sample [NIS] Analysis). Am J Cardiol. 2019 Jul 24. pii: S0002-9149(19)30812-4. doi:10.1016/j.amjcard.2019.07.015.

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