key: cord-278943-f80ucqqp
authors: Calvillo-Argüelles, Oscar; Abdel-Qadir, Husam; Ky, Bonnie; Liu, Jennifer E.; Lopez-Mattei, Juan C.; Amir, Eitan; Thavendiranathan, Paaladinesh
title: Modified Routine Cardiac Imaging Surveillance of Adult Cancer Patients and Survivors during the COVID-19 Pandemic
date: 2020-04-16
journal: JACC CardioOncol
DOI: 10.1016/j.jaccao.2020.04.001
sha: 
doc_id: 278943
cord_uid: f80ucqqp

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The COVID-19 pandemic has overwhelmed health care systems internationally, prompting difficult decisions and ethical dilemmas over resource allocation. (1) In-person healthcare encounters have been restricted to reduce exposures to patients and providers. These restrictions are particularly relevant to patients with cancer and/or cardiovascular disease (CVD) who have a greater risk of infection and worse outcomes with COVID-19.(2) Therefore, we must reconsider which in-person encounters, including imaging tests, are essential -where the risk of undetected CVD outweighs the risk of potential infection. The goal of this viewpoint is to provide general guidance, based upon available evidence, regarding the role of routine cardiac surveillance during this pandemic.(1) These are not societal guidelines and recommendations may change as the pandemic evolves.

While cardiac imaging surveillance through cancer treatment is a pillar of cardio-oncology practice, it is important to recognize that most recommendations are based on expert consensus.

Many routine tests have relatively low yield for detecting abnormal findings or modifying clinical care in asymptomatic patients.(3) Thus, it may be possible to adopt temporary measures during this pandemic which strike a balance between the early detection and prevention of cancer therapy related cardiac dysfunction (CTRCD) and risk of COVID-19 transmission. This requires individualizing imaging approaches to prioritize patients at the highest risk of CTRCD while deferring testing among lower-risk individuals. Importantly, we do not advocate completely omitting testing that would otherwise be clinically indicated. Rather, we attempt to prioritize cardiovascular imaging tests that should ideally be conducted without delay. For other patients, we should consider deferring tests to a later time-point after the pandemic resolves, when routine practices are more feasible.

Importantly, despite reduced surveillance, careful monitoring of symptoms, cardiovascular risk factor modification, and disease management should continue in all patients. This viewpoint will focus on surveillance for patients receiving anthracyclines and trastuzumab. There are no standard guidelines for routine imaging with other cardiotoxic therapies (e.g. VEGFi, immune check point inhibitors); this should remain unchanged.

The ASCO guidelines recommend baseline cardiac imaging for individuals receiving potentially cardiotoxic therapies such as anthracyclines and/or trastuzumab.(4) An implicit objective to these guidelines is the avoidance of longer-term rather than short-term cardiovascular risk. These guidelines define increased risk of CTRCD based on the planned treatment regimen and individual cardiovascular risk factors/comorbidities. Although baseline imaging can help identify patients at risk of CTRCD, it may be prudent to limit baseline testing during the pandemic to patients who are more likely to have abnormal testing or are at higher risk for CTRCD in the near-or medium-term, particularly if it may result in the initiation of cardioprotective medications or impact chemotherapy delivery (Table 1) .

Thus, with anthracycline initiation, regardless of dose, it may be reasonable to prioritize baseline cardiac imaging for patients with: 1) established or suspected CVD based on past medical history (e.g. myocardial infarction, cardiomyopathy, arrhythmia, moderate or greater valvular disease); 2) signs or symptoms of cardiac dysfunction; 3) ≥2 risk factors for CTRCD, including age ≥ 60 years, hypertension, diabetes, dyslipidemia, smoking, or obesity. Prior research indicates that overt CTRCD is unlikely in the near term in young patients without risk factors.(5) For other asymptomatic patients, we recommend optimizing risk factors prior to chemotherapy and deferring imaging after COVID-19 associated restrictions end.

When considering anthracycline dose as a risk factor for CTRCD, although we recognize that there is no safe dose, the risk rises substantially beyond 250mg/m 2 of doxorubicin-equivalent dose with even greater risk above 400mg/m 2 .(4) However, for adult patients whose only risk factor is high cumulative anthracycline dose, it may be reasonable to defer imaging until this high risk doses are reached or at the completion of anthracyclines. Since cardiac dysfunction rarely becomes clinically manifest at lower doses or before 3-6 months of treatment completion, this approach may allow identification and timely management of patients with CTRCD without baseline measurements. (6, 7) Baseline imaging is also commonly performed before trastuzumab initiation. Despite the high rates of trastuzumab-associated CTRCD, these patients often have a favorable clinical course.(8) Trastuzumab-associated CTRCD is less common without prior anthracycline exposure.(9) Baseline imaging prior to trastuzumab can be considered for women with: 1) preexisting CVD; 2) signs or symptoms of cardiac dysfunction; 3) ≥2 risk factors for CTRCD, including age ≥ 60 years, hypertension, diabetes, dyslipidemia, smoking, obesity; 4) exposure to anthracyclines as part of prior or current treatment regimen. However, if imaging in the past 6 months demonstrates normal cardiac function (LVEF ≥55%) and the absence of significant valvular disease, additional baseline testing can likely be deferred.

The optimal surveillance regimen during anthracycline chemotherapy remains incompletely In patients who develop CTRCD and require cardiac treatments and/or withholding of cancer therapy, repeat imaging should continue as per institutional standard of care.(10)

Current guidelines recommend long-term surveillance of adult survivors of pediatric, adolescent, and young adult cancers at higher risk based on patient characteristics and treatment exposures. (14, 15 ) Since this is a longer-term concern, it may be reasonable to defer routine screening in asymptomatic survivors during this pandemic. Currently there are no recommendations for routine surveillance in older adult cancer survivors; this should remain the standard unless patients develop HF symptoms.

Many patients will still require timely cardiac imaging. These studies should be performed with precautions to minimize the exposures (Table 2) , and The American Society of Echocardiography has developed guidance on how to practice echocardiography safely during this pandemic (https://www.asecho.org/ase-statement-covid-19/). Of note, there are also alternative imaging modalities that can be considered (Table 2) .

Several modifications to routine cardiac imaging practices in cancer patients can be considered during the COVID-19 pandemic. Since there are no data specific to these circumstances, our suggestions are not intended to change long-term practice. Rather, these are temporary measures where routine testing in asymptomatic patients may be deferred to minimize COVID-19

transmission. The suggestions are informed by existing literature in conjunction with our opinion which is borne from clinical experience. We recognize that some CTRCD events may be undetected. However, this likely poses a small absolute risk in the short-term. Any modifications to local practice patterns should not be enacted unilaterally. They need to be discussed collaboratively amongst cardiologists and oncologists and carefully with patients, who also need to be educated and informed, with individualization of practices to institutional and patientspecific needs. We believe that such approaches to reduce cardiac imaging during the COVID-19 pandemic will allow the cardio-oncology community to help in "flattening the curve." Use of imaging enhancing agents in non-Limit use of an imaging enhancement agent to non-

Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic

The Novel Coronavirus Disease (COVID-19) Threat for Patients with Cardiovascular Disease and Cancer

The yield of routine cardiac imaging in breast cancer patients receiving trastuzumab-based treatment: a retrospective cohort study

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers

The Risk of Heart Failure and Other Cardiovascular Hospitalizations After Early Stage Breast Cancer: A Matched Cohort Study

Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy

Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations With Ejection Fraction Decline, Recovery, and Heart Failure Symptoms Over 3 Years of Follow-Up

Safety of continuing trastuzumab despite mild cardiotoxicity. A Phase I Trial

Risk-Imaging Mismatch in Cardiac Imaging Practices for Women Receiving Systemic Therapy for Early-Stage Breast Cancer: A Population-Based Cohort Study

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry

Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

Trastuzumab-Related Cardiotoxicity and Cardiac Care in Patients With HER2 Positive Metastatic Breast Cancer

Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group

MUGA scans) which can be performed rapidly while minimizing patient/ technologist exposure

Dr. Calvillo-Argüelles is supported by the Hold'em for Life Oncology Clinician Scientist Award at the University of Toronto's Faculty of Medicine. Dr. Ky is supported by NIH R01 HL118018 and an AHA Transformational Project Award. Dr. Thavendiranathan (147814) is supported by the Canadian Institutes of Health Research New Investigator Award.

Baseline imaging prior to treatment with potentially cardiotoxic therapies. (4) (10) 1. Prior history of CVD (e.g. MI, cardiomyopathy, arrhythmia, moderate or greater valvular disease) 2. Signs and symptoms of cardiac dysfunction 3. ≥ 2 risk CV factors for CTRCD * 4. Exposure to anthracycline as part of current or prior treatment ‡ During Treatment -Anthracycline Treatment ASCO -Routine imaging surveillance may be considered in asymptomatic patient patients considered at increased risk of cardiac dysfunction with frequency determined by health care provider based on clinical judgement(4) ESMO -after each additional 100 mg/m 2 beyond 250 mg/m 2 as (10) Repeat imaging early upon diagnosis of CTRCD to guide re-initiation of cancer therapy or titrate cardiac medications.

individuals during pandemic, but return to institution specific protocols post-pandemic. 2. Consider in those with HF signs/symptoms, high doses of doxorubicin-equivalent (e.g. ≥400mg/m 2 ), or those reaching 250mg/m 2 with prior CVD or multiple CV risk factors * with a continued need for anthracyclines.

During Treatment -Trastuzumab Variability in practice, FDA package insert recommends baseline imaging and every 3 months during duration of trastuzumab therapy Repeat imaging early upon diagnosis of CTRCD to guide re-initiation of cancer therapy or titration of cardiac medications.