Introduction

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people across the world and severely disrupted the delivery of health care. Recent studies have demonstrated that patients with preexisting cardiovascular disease and/or cancer are at increased risk of infection and life-threatening complications due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There has been a high prevalence of cardiovascular comorbidities among patients with COVID-19, particularly in those with severe disease.^1-3 Recent case series also report a significant increase in severe outcomes (i.e., intensive care unit admission and need for mechanical ventilation) and case fatalities among patients with cancer with COVID-19.^4,5 Based upon these findings, cardio-oncology patients are likely to be particularly susceptible to poor outcomes from COVID-19 given their compromised immune system and limited cardiopulmonary reserve related to coexistent cancer and cardiovascular disease.⁶ The imperative to prevent SARS-CoV-2 infection while providing cardiovascular care in this high-risk population calls for a modified approach to the delivery of cardio-oncology care during the pandemic.

Cardiac Surveillance Before, During, and After Cancer Treatment

Monitoring of left ventricular (LV) function before, during, and after cancer treatment is an important aspect of cardio-oncology care, given the early and late adverse cardiac effects associated with many cancer treatments, including anthracyclines, targeted therapies, and radiotherapy. However, due to the potential risk of COVID-19 exposure associated with in-person visits for cardiac imaging, a temporary modification of the standard practice for cardiac imaging during cardiotoxic cancer treatment should be considered. For example, greater flexibility in the timing and/or an option to forego surveillance cardiac imaging at certain timepoints could be considered in asymptomatic patients, especially those free of significant cardiovascular disease at the most recent assessment. Assessing patient-specific and treatment-specific risk factors for cardiotoxicity can be useful for making this determination. In patients who have any clinical signs or symptoms suggestive of possible cardiac dysfunction, cardiac imaging should be performed without delay.

The following is a proposed general framework for modifying cardiac surveillance in patients with breast cancer during the COVID-19 pandemic (Figure 1):

• Patients at Increased Risk for Cardiotoxicity. There is a continuum of cardiotoxicity risk based upon several factors, including the following:
  • History of cardiovascular disease (e.g., cardiomyopathy, coronary heart disease, valvular heart disease, and arrhythmia)
  • Presence of multiple cardiovascular risk factors such as hypertension, diabetes, hyperlipidemia, obesity, and age ≥60
  • Previous treatment with cardiotoxic therapies such as anthracyclines or radiotherapy with significant heart exposure
    
    
  In patients deemed to be at increased risk based on the above factors, it is our practice to recommend standard of care cardiac surveillance at routine intervals (before, during, and after treatment) per institutional guidelines.
  
  
• Patients at Low Risk for Cardiotoxicity. For patients without any of the above risk factors, modifications to routine cardiac surveillance can be considered to reduce risk of COVID-19 exposure, based on the cancer-treatment regimen:
  • Anthracyclines only
    • Before treatment, consider foregoing a baseline LV ejection fraction (LVEF) assessment.
    • During treatment, consider an interval LV assessment at a doxorubicin equivalent dose ≥250 mg/m², particularly if findings from the study will influence decisions regarding the type or duration of additional cancer treatment. Perform LVEF surveillance at a doxorubicin equivalent dose ≥400 mg/m² and at regular intervals thereafter if additional anthracyclines are needed.
    • After treatment, postpone routine cardiac surveillance.
  • Trastuzumab (without prior anthracyclines)
    • Before treatment, consider foregoing a baseline LVEF assessment.
    • During treatment, in place of current recommendations to repeat LVEF assessments every 3 months during trastuzumab, consider reduced surveillance at 6 and 12 months only.
    • After treatment, postpone routine cardiac surveillance.
  • Anthracyclines and trastuzumab
    • Before treatment, a baseline LVEF assessment is advised with an anthracycline-based trastuzumab regimen because an abnormal finding may influence the decision to pursue a less-cardiotoxic treatment regimen.
    • During treatment, current guidelines recommend repeat LVEF assessments before and every 3 months for trastuzumab. A 4- to 6-week delay in imaging may be allowed during periods of high risk for COVID-19 or reduced access to cardiac imaging facilities.
    • After treatment, postpone routine cardiac surveillance.

Figure 1: A Proposed Algorithm for Modified Cardiotoxicity Surveillance of Patients With Breast Cancer During the COVID-19 Pandemic

In JACC CardioOncology, Calvillo-Arguelles et al. provide general guidance on best practices for performing cardiac surveillance in adult patients with cancer and cancer survivors during the COVID-19 pandemic, emphasizing the need to balance the potential benefit of early detection of cancer therapy-related cardiac dysfunction with the risk of COVID-19 transmission or infection of patients and health care professionals.⁷ The American Society of Echocardiography has issued recommendations on safe practices to decrease both provider and patient exposure risk during the pandemic.⁸ Alternative imaging modalities such as multigated acquisition scans or non-contrast cardiac magnetic resonance imaging reduce the duration of face-to-face contact between patients and technologists and can be considered in lieu of an echocardiogram. Any modifications to current standards for cardiac surveillance during cancer treatment should be made in concert with ongoing clinical assessments to monitor for cardiac symptoms and serve as temporary measures until the pandemic resolves sufficiently to allow patients to be treated safely.

Cardiac biomarkers such as cardiac troponins and natriuretic peptides have been proposed as additional tools for the risk stratification and early detection of cardiotoxicity.^9,10 In a recent study by Demissei et al., elevated high-sensitivity troponin T assessed after completion of anthracyclines or interval increases in N-terminal pro-B-type natriuretic peptide during sequential anthracycline and trastuzumab therapy were predictive of subsequent cardiotoxicity in patients with breast cancer.¹¹ The wide availability and ease of biomarker testing as well as the limited duration of close contact required for phlebotomy could conceivably allow for the identification of higher-risk patients, who would then be referred for echocardiography, thus limiting exposure risk to both health care providers and patients. Data are needed, however, to determine the negative predictive value for cardiotoxicity of normal levels of high-sensitivity troponin or B-type natriuretic peptide.

Cardio-Oncology Consultation During the Pandemic

The COVID-19 pandemic raises many difficult questions about how and when to deliver treatment to patients with cancer and what safeguards are needed to ensure the safety of patients and health care providers. Nationwide mandates to stay at home have delayed diagnostic testing and treatment. Video conferencing for virtual appointments has been rapidly adopted in health systems across the United States as a means to continue delivering oncology and cardio-oncology care while protecting patients, health care professionals, and communities from COVID-19.¹²

Telemedicine is well suited to address many of the clinical issues that are frequently encountered in a cardio-oncology clinic, such as heart failure, hypertension, arrhythmia, or coronary artery disease.¹³ Further, telemedicine increases patient access to cardio-oncology care given the enhanced scheduling flexibility, elimination of the need for travel along with its inherent delays and costs, and a dramatic reduction in the need for brick-and-mortar resources that are often in short supply. Many patients are already equipped to measure heart rates, blood pressures, and weights from home, and this information can be incorporated with a limited telemedicine physical exam to make clinical assessments and provide treatment recommendations. Smart phones are nearly universal or can be provided to the patient at minimal cost. Telemedicine platforms through Doximity, WhatsApp, Jabber, Facetime, and other platforms are evolving at light speed. It will be important to carefully study patient outcomes in cardio-oncology based on the telemedicine virtual approach versus face-to-face encounters over a wide range of cardio-oncology presentations. Continued growth of telehealth technology, including personal devices for at-home electrocardiogram monitoring, remote arrhythmia-monitoring devices, and more sophisticated digital monitors of vascular or physiologic parameters, will further enhance the capabilities of a telemedicine encounter.

As health care systems begin to recover from the COVID-19 pandemic, there will be a surge of patients in need of cancer-related care that was delayed. Clinical demand (i.e., new patient referrals, preoperative consultations, or follow-up visits for new or ongoing cardiotoxicity) may grow gradually during the early phases of recovery but likely will eventually exceed pre-COVID-19 levels. Preparations by cardio-oncology clinics to accommodate this anticipated surge of patients are needed to maintain social distancing in the workplace and to assure the safest possible work environment. This includes provision of appropriate personal protective equipment, staggered work hours, and ongoing telecommuting so that only the minimum number of necessary staff members is onsite at any given time. Other strategies to mitigate risk of exposure or transmission to high-risk cardio-oncology patients include a reconfiguration of waiting room seating to increase space between patients and a change in patient flow to reduce the amount of time spent in communal spaces while waiting to receive care.

Considerations for Cardio-oncology Care During the Pandemic

QT Monitoring

QT prolongation is common in patients with cancer due to several factors, including use of cancer therapies (e.g., arsenic trioxide, tyrosine kinase inhibitors, or ribociclib) or supportive medications (e.g., antiemetics or antimicrobials) that prolong the QT interval, coexisting cardiovascular disease, and electrolyte disturbances related to cancer therapy-induced nausea, vomiting, or dehydration. Treatment with hydroxychloroquine and/or azithromycin, which were considered to be promising treatments for COVID-19, may further increase susceptibility of life-threatening arrhythmias in patients with cancer.¹⁴ Recommendations for QT monitoring have been provided by the American College of Cardiology (ACC) and Heart Rhythm Society, which suggest avoidance of other QT-prolonging medications when feasible, individualized risk assessment for QT prolongation using the Tisdale risk score, and use of telemetry over 12-lead electrocardiograms when feasible to minimize practitioner exposure risk if QT monitoring is indicated.^15,16 Discussions between cardiologists and oncologists should be initiated early to determine the optimal approach for QT monitoring. Future use of hydroxychloroquine may decline given that two recently published observational studies did not show an association between hydroxychloroquine and mortality.^17,18 Clinical trials are ongoing to definitively evaluate the efficacy of hydroxychloroquine in COVID-19, and continued vigilance for QT monitoring is warranted.

Renin Angiotensin Aldosterone System Antagonists

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are common medications used for the management of hypertension and systolic LV dysfunction in patients with cancer receiving cardiotoxic therapy. ACE inhibitors and ARBs upregulate the expression of the ACE2 receptor utilized by SARS-CoV-2 for entry into host cells,¹⁹ raising concerns that treatment with these medications increases risk for COVID-19 infection. Early during the COVID-19 pandemic, a joint statement from the Heart Failure Society of America (HFSA), the ACC, and the American Heart Association (AHA) encouraged clinicians to continue these medications if clinically indicated given the absence of data on their effect on COVID-19 infection or outcomes.²⁰ Three studies recently published in The New England Journal of Medicine report no association between treatment with ACE inhibitors or ARBs and risk of COVID-19 infection or mortality and provide important data in support of the ACC/AHA/HFSA recommendations.^21-23

Corticosteroids

Corticosteroids are a first-line treatment in patients with immune checkpoint inhibitor-associated adverse events including myocarditis.²⁴ However, speculation that immunosuppressive effects of steroids may increase the risk of COVID-19 infection or cause harm among infected patients raises the question whether their use should be limited.²⁵ Currently, insufficient evidence exists for or against the use of corticosteroids in the setting of COVID-19; therefore, the use of these medications should be guided by currently accepted clinical indications.

Conclusion

The delivery of cancer and cardio-oncology care in the post-pandemic era will be significantly different from the approach prior to the existence of COVID-19, with a continued transition from face-to-face encounters to the use of telehealth. A modified approach to routine cardiotoxicity surveillance during cancer therapy should be pursued to balance the benefit of early detection of cancer therapy-related cardiac dysfunction with the potential risk of COVID-19 exposure. Ongoing research is needed to establish evidence-based guidelines that optimize the approach to cardiac surveillance during cancer treatment and ensure the highest level of cardiac safety without overutilizing health care resources. Increased use of remote monitoring solutions will spur investment and innovation in novel digital solutions and enable health care professionals to provide high-quality care.

References

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Clinical Topics: Cardio-Oncology, COVID-19 Hub, Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Novel Agents, Statins

Keywords: Cardio-oncology, Cardiotoxicity, COVID-19, Coronavirus, severe acute respiratory syndrome coronavirus 2, Pandemics, Anthracyclines, Cardiovascular Diseases, Troponin T, Breast Neoplasms, Risk Factors, Natriuretic Peptide, Brain, Phlebotomy, Hyperlipidemias, Peptidyl-Dipeptidase A, Antiemetics, Angiotensin Receptor Antagonists, Hydroxychloroquine, Angiotensin-Converting Enzyme Inhibitors, Mineralocorticoid Receptor Antagonists, Coronary Artery Disease, Azithromycin, American Heart Association

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