Prevention of heart failure and cardiomyopathy in patients with cancer

Establishing a patient’s cardiovascular risk

The American College of Cardiology’s Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator Plus allows clinicians to calculate a patient’s 10-year risk for ASCVD (primary prevention only). It considers a patient’s age, race, gender, blood pressure, cholesterol (total cholesterol and high-density lipoprotein), history of diabetes mellitus and hypertension, history of tobacco use, and aspirin use. Based on the calculated 10-year risk for ASCVD, the patient’s risk is classified as low (<5%), borderline (5% to 7.4%), intermediate (7.5% to 19.9%), and high (≥20%). Depending on the patient’s risk, preventative strategies, such as initiating statin therapy, are recommended. It is important to emphasize that none of these risk assessment calculators has been validated in the cancer population, especially those who have had prior cancer therapy.

Certain cancers (e.g., lung cancer, multiple myeloma) have an inherently higher risk of CV complications, and this is frequently coupled with treatment-related CV adverse effects (e.g., radiation-induced heart disease, drug-related cardiac dysfunction).

Patients with known CV disease, such as coronary artery disease and peripheral vascular disease should be screened for symptoms, and medical optimization should be pursued when possible. Knowing the extent of their CV disease and prior cancer treatment plays a key role when providing recommendations about the patient’s risk with certain cancer therapies (e.g., a tyrosine kinase inhibitor, such as nilotinib) that are associated with increased risk for vascular toxicity (e.g., development of atherosclerosis, endothelial dysfunction, thrombosis, or vasospasm). Additionally, certain cancer therapies (e.g., high-dose cytarabine) have important hematologic complications (e.g., thrombocytopenia) that could preclude guideline-based therapy. Anticipating these issues becomes critically important—for example, the use of dual antiplatelet agents in patients with recent percutaneous coronary intervention who are undergoing treatment for a hematologic malignancy.

The differential diagnosis of heart failure (HF) in the oncology population is essentially the same as for the general population, except for the complications that may arise from cancer itself or its therapy. Table 7.1 provides a list of possible causes of HF in this population. In general, cardiomyopathy or (CM) or HF can result from any combination of direct cardiotoxic effects from the cancer itself (e.g., multiple myeloma, amyloidosis), cardiotoxic treatments (e.g., anthracyclines), or as an exacerbation of a preexisting CV disease or a systemic condition (e.g., sepsis).

Treatment of patients with congenital heart disease is particularly challenging, because, in many cases, there are residual structural abnormalities even if surgically corrected. Hemodynamic compromise may result during cancer treatment because of fluid changes, such as with dehydration and anemia.

Treatment-related risk

Understanding the risk of left ventricular (LV) dysfunction and HF associated with different chemotherapy agents is necessary when planning a safe and personalized treatment regimen.

Risk factors specific to patients with cancer include prior anthracycline therapy and chest or mediastinal radiation.

It is well recognized that anthracycline cardiotoxicity is dose-dependent and there is no safe dose. Knowing the cumulative dose allows clinicians to consider different protective strategies, such as anthracycline dose reduction, continuous versus bolus infusion to avoid peak levels, ^, liposomal doxorubicin, ^, and dexrazoxane. ^, This is especially crucial in cases where the benefits of anthracycline therapy outweigh its risks.

Unlike anthracyclines, the decline in ejection fraction is classically seen at the time of therapy for trastuzumab and recovers in most cases upon cessation of therapy, although irreversible declines and persistent reduction in cardiac function have been described as well; patients receiving trastuzumab after anthracycline therapy are considered to represent the highest risk group.

The 2016 American Society of Clinical Oncology (ASCO) practice guidelines consider those patients with cancer at high risk for cardiotoxicity if they are receiving a cumulative doxorubicin dose 250 mg/m ² or greater, chest radiation 30 Gy or greater with the heart in the radiation field, combination of these two even at lower dose cutoffs, anthracycline at any dose, trastuzumab in combination with with either anthracycline or radiation therapy, or CV risk factors or CVD ( Table 7.2 ).

Efforts have been pursed to express the overall cardiotoxicity risk as an integral score based on patient and treatment-related risk factors, but these are conceptual models in need of validation. At present not sufficient data support either a universal cardiotoxicity risk prediction model (either for all patients and therapies or for one therapy and all possible cardiovascular toxicities), given the heterogeneity of variables involved. Identifying patients at risk for cardiotoxicity from cancer treatment remains a challenge in clinical practice, even when focus is only on one drug and one patient population such as trastuzumab in patients with breast cancer.

Radiation-induced heart disease (RIHD) consists of a series of events that ultimately lead to myocardial dysfunction and HF. It involves direct and indirect vascular damage and upregulation of inflammatory markers that can result in ischemia, thrombosis, and stenosis of the major vessels (e.g., coronary artery disease, superior vena cava syndrome). It also has a detrimental effect on cardiac valves, which may result in calcification leading to significant regurgitation and/or stenosis.

Pericardial disease can manifest as constrictive pericarditis in patients with prior chest radiation or as pericardial effusion and/or tamponade caused by inflammation, medications (e.g., high-dose cyclophosphamide), or malignant involvement.

Immune checkpoint inhibitors are associated with rare, but sometimes fatal, cardiovascular immune-related adverse events, particularly myocarditis. Nonetheless, other manifestations include pericardial disease, ^, vasculitis, Takotsubo cardiomyopathy, conduction abnormalities, and destabilization of atherosclerotic lesions.