TABLE 5.
Best Practices for the Prevention and Management of Cardiac Complications in Patients With Cancer in the Coronavirus Disease 2019 (COVID-19) Era
| 2020 ESMO CONSENSUS RECOMMENDATION | ICOS CONSENSUS RECOMMENDATION IN THE COVID-19 ERA |
|---|---|
| 1. General principles | |
| 1.1. Screening for known CV risk factors in patients with cancer is recommended; treatment of identified CV risk factors according to current guidelines is recommended (LOE, I; GOR, A) | 1.1. Continuing approval without change |
| 1.2. Many types of cancer therapy, especially mediastinal and left-sided chest radiation and certain chemotherapy and targeted agents, can substantially affect the heart and vascular system, and it is recommended that CV safety be monitored (LOE, I; GOR, A) | 1.2. Continuing approval without change |
| 1.3. Close and early collaboration between cardiologists, oncologists, hematologists, and radiation oncologists is recommended to ensure lifelong CV health and to avoid unnecessary discontinuation of cancer therapy (LOE, III; GOR, C) | 1.3. Continuing approval without change |
| 2. Baseline CV risk assessments (precancer therapy) | |
| 2.1. Routine use of cardiac biomarkers (cardiac troponins I or T [TnI or TnT] and B-type natriuretic peptide [BNP], or N-terminal pro-BNP [NT pro-BNP]) for patients undergoing potentially cardiotoxic chemotherapy is not well established; however, for high-risk patients (with preexisting, significant CVD) and those receiving high doses of cardiotoxic chemotherapy such as an anthracycline, baseline measurement of such cardiac biomarkers should be considered (LOE, III; GOR, A) | 2.1. Continuing approval without change |
| 2.2. For patients with a cancer diagnosis that requires treatment with a potentially cardiotoxic treatment, a baseline electrocardiogram (ECG), including measurement of a heart rate-corrected QT interval (QTc), is recommended (LOE, I; GOR, A): QTc should be calculated by either of the 2 most standardized methods—Bazett or Fridericia—and the comparative measurements during treatment should all be done using the same method | 2.2. Continuing approval without change |
| 2.3. In patients scheduled to undergo cancer therapy associated with heart failure or left ventricular (LV) dysfunction, baseline evaluation of left ventricular ejection fraction (LVEF), with strain imaging when possible, and diastolic function according to accepted comprehensive imaging practice is recommended (LOE, I; GOR, A) | 2.3. Transthoracic echocardiogram (with or without strain imaging) and cardiac MRI (with or without strain) are the recommended imaging modalities |
| 3. Primary prevention therapy | |
| 3.1. In patients with a normal LVEF scheduled to undergo cancer therapy with known cardiotoxic agents and risk factors for cardiac toxicity, prophylactic use of angiotensin-converting enzyme inhibitors (ACE-Is) or, alternatively, angiotensin receptor blockers (ARBs), and/or selected β-blockers (BBs) may be considered to reduce the risk of cardiotoxicity; dexrazoxane has been validated as a cardioprotectant in selected populations who are receiving anthracycline-based chemotherapy (LOE, II; GOR, B) | 3.1. Continuing approval without change |
| 3.2. Patients with evidence of hyperlipidemia may benefit from treatment during active cancer therapy, especially cardiotoxic chemotherapy (LOE, II; GOR, C) | 3.2. Continuing approval without change |
| 4. During cancer treatment: Cardiac safety surveillance | |
| 4.1. The following general principles are recommended for medical imaging in patients with cancer at risk for cardiac complications particularly for the periodic assessment of LV systolic function: | 4.1. Continuing approval without change |
| 4.1.1. Highly reproducible, quantitative volumetric, nonirradiating imaging with quality control is recommended (quantitative 2-dimensional [2D] and 3-dimensional [3D] echocardiography, and cardiac MRI) (LOE, I; GOR, A) | |
| 4.1.2. For each patient, the same imaging modality at the same facility is highly recommended for serial testing (LOE, I; GOR, A) | |
| 4.1.3. LV global longitudinal strain (GLS) imaging may be considered, when available, for baseline and serial LV systolic function monitoring (LOE, III; GOR, C) | |
| 4.2. Asymptomatic patients receiving anthracycline-based chemotherapy with no cardiac biomarker or imaging abnormalities should undergo surveillance for risk stratification and the early detection of cardiac toxicity | 4.2. Measurement of cardiac biomarkers (TnI or TnT and BNP, or NT-proBNP) should be considered in conjunction with cancer treatment safety laboratories if obtained with each cycle of chemotherapy; if either cardiac biomarker (TnI or TnT and BNP or NT-proBNP) is abnormal at the assay-specific cutoff and/or the patient becomes symptomatic, reassessment of LVEF with or without GLS should be performed using either 2D or 3D echocardiography, or cardiac MRI |
| 4.2.1. Periodic (every 3–6 wk or before each cycle) measurement of TnI or TnT and BNP or NT-proBNP using the same institutional laboratory using an acceptable 99% upper limit of normal reference range as the threshold for abnormal (LOE, III; GOR, C) | |
| 4.2.2. Reassessment of LVEF and GLS (when possible) following the general imaging principles is recommended after a cumulative dose of 250 mg/m2 of doxorubicin or its equivalent anthracycline, after approximately each additional 100 mg/m2 (or approximately 200 mg/m2 of epirubicin) beyond 250 mg/m2, and at the end of therapy, even if the cumulative dose is <400 mg/m2 (LOE, I; GOR, A) | |
| 4.3. Aligned to the current recommendations by the FDA for asymptomatic, nonmetastatic patients undergoing adjuvant trastuzumab treatment, routine surveillance, consisting of cardiac imaging every 3 mo, should be considered for the early detection of cardiac toxicity; however, the effective-ness of this strategy in patients at low CV risk with no evidence of early LV dysfunction has not been demonstrated (LOE, II; GOR, B) | 4.3. In patients who remain asymptomatic and who have normal or less than a 50% increase in cardiac biomarkers during monitoring, cardiac imaging is not recommended |
| 4.4. Cardiac biomarker assessment may be considered as a valuable tool for cardiac safety surveillance in patients receiving adjuvant anti-HER2–based treatment (LOE, III; GOR, C) | 4.4. Cardiac imaging should be performed only when patients become symptomatic or have abnormal cardiac biomarkers |
| 4.5. Asymptomatic patients receiving anti-HER2–based treatment (trastuzumab, pertuzumab, T-DM1) for metastatic disease should have general surveillance for cardiac toxicity that may consist of periodic physical examination, cardiac biomarkers, and/or cardiac imaging (LOE, I; GOR, B) | 4.5. Continuing approval without change; the threshold to obtain cardiac imaging should be higher in the COVID-19 era, but continued surveillance for the detection of new symptoms or elevation of cardiac biomarkers is unchanged |
| 4.6. In patients receiving cancer therapeutics associated with a risk of systemic hypertension, especially anti-VEGF-based therapy, establishment of a baseline blood pressure measurement and serial blood pressure monitoring is recommended along with surveillance for the early detection of CV toxicity that may consist of periodic cardiac examination, cardiac biomarkers, and/or cardiac imaging (LOE, I; GOR, A) | |
| 5. During cancer treatment: Asymptomatic, new laboratory abnormalities (or preclinical toxicity) | |
| 5.1. In asymptomatic patients receiving treatment with anthracyclines who have an LVEF decrease of ≥10% from baseline to <50% or decrease in LVEF to ≥40% but <50%, the following evaluations are recommended (LOE, III; GOR, A): | 5.1. This recommendation remains the same, except for repeating LVEF with or without GLS after every other dose of anthracycline-based chemotherapy; it is recommended to monitor patients by checking cardiac biomarkers (TnI or TnT and BNP or NT-proBNP) every other cycle, and reassessing LV function with imaging only if either biomarker is abnormal or the patient develops heart failure symptoms. The determination for the presence of heart failure symptoms can be obtained by telemedicine |
| 5.1.1. Cardiology consultation (preferably a cardio-oncology specialist) | |
| 5.1.2. Consider initiation of cardioprotective treatment (ACE-I or ARB with or without BB, and perhaps a statin), if not already prescribed | |
| 5.1.3. Consider measuring cardiac biomarkers (TnI or TnT and BNP or NT-proBNP) and perform a cardiac-focused physical examination after each dose of anthracycline | |
| 5.1.4. Repeat LVEF with or without GLS measurement after every other dose of anthracycline-based chemotherapy | |
| 5.1.5. If further anthracycline therapy is planned, the benefit-risk assessment of continued anthracycline-based therapy as well as options of nonanthracycline regimens should be discussed, and there should be consideration for the use of dexrazoxane and/or liposomal doxorubicin | |
| 5.2. In asymptomatic patients receiving treatment with trastuzumab who have an LVEF decrease of ≥10% from baseline to <50% or have a decrease in LVEF to ≥40% but <50%, the following evaluations are recommended (LOE, III; GOR, A): | 5.2. If the baseline LVEF with or without GLS is within normal range and the patient is asymptomatic while on treatment with trastuzumab, cardiac biomarkers (TnI or TnT and BNP or NT-proBNP) can be measured every other cycle; cardiac imaging with either echocardiography or cardiac MRI is recommended only if any cardiac biomarker is abnormal or the patient develops heart failure symptoms |
| 5.2.1. Cardiology consultation (preferably a cardio-oncology specialist) | |
| 5.2.2. Consider initiation of cardioprotective treatment (ACE-I or ARB with or without BB), if not already prescribed | |
| 5.2.3. Consider measuring cardiac biomarkers (TnI or TnT and BNP or NT-proBNP) at a suggested interval of every 4–6 wk and periodic cardiac-focused physical examination for ongoing monitoring of cardiac toxicity | |
| 5.2.4. Repeat LVEF with or without GLS measurement within 3–6 wk after holding trastuzumab, and, if LVEF with or without GLS has normalized, trastuzumab therapy can be resumed | |
| 5.3. In asymptomatic patients receiving treatment with any cardiotoxic cancer therapy who have a normal LVEF but a decrease in average GLS from baseline assessment (≥12% relative decrease or ≥5% absolute decrease), the following evaluation and treatment should be considered (LOE, III; GOR, B): | 5.3. Continuing approval without change |
| 5.3.1. Consider initiation of cardioprotective treatment (ACE-I or ARB with or without BB), if not already prescribed | |
| 5.3.2. Repeat LVEF with or without GLS measurement every 3 mo, or sooner, if cardiac symptoms develop | 5.3.2. Cardiac imaging should be performed in patients with abnormal cardiac biomarkers or in those who develop cardiac symptoms |
| 5.3.3. Consider measuring cardiac biomarkers (TnI or TnT and BNP or NT-proBNP) as needed based on the cancer treatment’s risk of cardiac toxicity | |
| 5.3.4. Life-saving cancer treatment should not (?) be altered solely based on changes in LV strain | |
| 5.4. In asymptomatic patients undergoing treatment with cardiotoxic anticancer therapy and an have elevation in cardiac troponin, the following measures should be considered (LOE, III; GOR, C): | 5.4. Continuing approval without change |
| 5.4.1. Cardiology consultation, preferably a cardio-oncology specialist | |
| 5.4.2. Consider LVEF and GLS assessment with echocardiography | |
| 5.4.3. Appropriate evaluation to exclude ischemic heart disease as a comorbidity | |
| 5.4.4. Consider initiation of cardioprotective treatments (ACE-Is, ARBs and/or BBs), if not already prescribed | |
| 5.4.5. Consider initiation of dexrazoxane in patients undergoing anthracycline-based chemotherapy | |
| 5.4.6. It is possible that anticancer therapy may be continued without interruption if only mild elevations in cardiac biomarkers occur without significant LV dysfunction | |
| 6. During cancer treatment: Clinical cardiac dysfunction | |
| 6.1. In patients with an abnormal LVEF <50% but ≥40%, medical therapy with an ACE-I (or ARB) and/or BB is recommended before starting potential cardiotoxic treatment (LOE, I; GOR, A) | 6.1. Continuing approval without change |
| 6.2. For those with an LVEF <40%, anthracycline therapy, in particular, is not recommended unless there is no other effective alternative cancer treatment option (LOE, IV; GOR, A) | 6.2. Continuing approval without change |
| 6.3. For a patient receiving treatment with any cardiotoxic agent who presents with potentially cardiac-related but unexplained signs and symptoms, such as (but not limited to) sinus tachycardia, rapid weight gain, dyspnea, peripheral edema, or ascites, it is recommended to obtain a cardio-oncology consultation, reassess LVEF with or without GLS, and potentially measure cardiac biomarkers (LOE, III; GOR, A) | 6.3. It is recommended to obtain cardiac biomarkers and discuss with a cardio-oncologist if cardiac imaging is warranted |
| 6.4. For a patient receiving treatment with trastuzumab (or any HER2-targeted molecular therapy) who has signs and symptoms of heart failure, or for an asymptomatic patient with an LVEF <40%, the same assessments as those for an LVEF ≥40% are recommended; in addition, trastuzumab (or any HER2-targeted molecular therapy) should be held until the cardiac status has stabilized, and a discussion regarding the risk/benefits of continuation should be held with the multidisciplinary team and the patient (LOE, I; GOR, A) | 6.4. It is recommended to obtain cardiac biomarkers and discuss with a cardio-oncologist if cardiac imaging is warranted |
| 6.5. For a patient in whom trastuzumab (or any HER2-targeted molecular therapy) has been interrupted, whose LVEF has increased to ≥40%, and/or whose signs and symptoms of heart failure have resolved, resumption of trastuzumab (or any HER2-targeted molecular therapy) should be considered, along with the following recommendations (LOE, III; GOR, B): | 6.5. Continuing approval without change |
| 6.5.1. Continued medical therapy for heart failure and ongoing cardiology care | |
| 6.5.2. Periodic cardiac biomarker (BNP or NT-proBNP) assessment | 6.5.2. Periodic cardiac biomarker (BNP or NT-proBNP) assessment should be performed at a frequency determined by the treating physician considering the patient’s clinical presentation and risk of cardiac toxicity |
| 6.5.3. Periodic LVEF assessments during ongoing treatment | 6.5.3. LVEF assessment is recommended only in the setting of an abnormal cardiac biomarker and/or worsening symptoms of heart failure |
| 6.6. For a patient in whom trastuzumab (or any HER2-targeted molecular therapy) has been interrupted, whose signs and symptoms of heart failure do not resolve, cardiac biomarker does not normalize, and/or LVEF remains <40%, resumption of trastuzumab may be considered if no alternative therapeutic options exist; the risk-benefit assessment of prognosis from cancer versus heart failure should be discussed with the multidisciplinary team and the patient (LOE, IV; GOR, C) | 6.6. Continuing approval without change |
| 6.7. For a patient receiving treatment with sunitinib (or any other anti-VEGF based therapy) with signs and symptoms of heart failure, assessment of blood pressure control is recommended and measurement of LVEF and/or cardiac biomarkers should be considered; in addition, sunitinib (or any other anti-VEGF–based therapies) should be interrupted until the appropriateness of reinstituting this therapy has been fully assessed (LOE, III; GOR, A) | 6.7. It is first recommended to assess blood pressure control and cardiac biomarkers; if cardiac biomarkers are abnormal and/or symptoms of heart failure worsen despite achieving adequate blood pressure control, measurement of LVEF is then recommended; early involvement of a cardio-oncologist is strongly recommended to guide choice of antihypertensive therapy |
| 7. Survivors of cancer therapy (posttreatment) | |
| 7.1. For asymptomatic patients who have been treated with cardiotoxic agents and have normal cardiac function, periodic screening for the development of new asymptomatic LV dysfunction with cardiac biomarkers and, potentially, cardiac imaging should be considered at 1-y and 2-y posttreatment, and periodic reassessment thereafter should be considered (LOE, III; GOR, B) | 7.1. A thorough history, including assessment of CV risk factor control, should be performed along with cardiac biomarkers; these should then guide the decision about assessing LVEF with or without GLS; early consultation with a cardiologist or cardio-oncologist is strongly recommended; if prior imaging was significantly abnormal (ie, valvular or pericardial disease), the interval for reassessment should not be excessively delayed |
| 7.2. For patients who developed asymptomatic LV dysfunction or heart failure because of trastuzumab (or any other HER2-targeted molecular therapy), anthracycline, or other cancer therapy, CV care, including medical treatment with ACE-I (or ARB) and/or BB and regular CV evaluation (eg, annually, if asymptomatic), should be continued indefinitely, regardless of improvement in LVEF or symptoms; any decision to withdraw guideline-based medical therapy should only be done after a period of stability, no active cardiac risk factors, and no further active cancer therapy (LOE, II; GOR, B) | 7.2. Decision about withdrawing any cardiac medications should first be discussed with the patient’s cardio-oncologist |
| 7.3. For patients with a history of mediastinal or chest radiation, evaluation for coronary artery disease and myocardial ischemia as well as valvular heart disease is recommended, even if asymptomatic, starting at 5 y posttreatment and then at least every 3–5 y thereafter (LOE, I; GOR, A) | 7.3. Any routine CV imaging should be postponed until COVID-19 restrictions are suspended as long as the patient is asymptomatic; symptom awareness, optimal CV risk factor management, and occasional cardiac biomarker assessment should continue at the recommended intervals |
| 8. Immune checkpoint inhibitor-associated CV toxicity | |
| 8.1. For patients who develop new CV symptoms or are incidentally noted to have any arrhythmia, conduction abnormality on ECG, or LVSD on echocardiogram while undergoing (or after recent completion) of immune checkpoint inhibitor (ICI) therapy, further appropriate work-up (ECG, troponin, BNP or NT-pro-BNP, C-reactive protein, viral titer, echocardiogram with GLS, cardiac MRI) for ICI-associated CV toxicity, particularly myocarditis and other common differential diagnoses, should be carried out promptly (LOE, IV; GOR, C) | 8.1. Continuing approval without change |
| 8.2. Endomyocardial biopsy for diagnosis should be considered if the diagnosis is highly suspected with otherwise negative work-up (LOE, IV; GOR, C) | 8.2. Continuing approval without change |
| 8.3. With either suspicion or confirmation of ICI-associated myocarditis, further therapy with ICIs should be withheld, and high-dose corticosteroids (methylprednisolone 1000 mg/d followed by oral prednisone 1 mg/kg/d) should be initiated promptly; corticosteroids should be continued until resolution of symptoms and normalization of troponin, LV systolic function, and conduction abnormalities (LOE, IV; GOR, C) | 8.3. Continuing approval without change |
| 8.4. For steroid-refractory or high-grade myocarditis with hemodynamic instability, other immunosuppressive therapies, such as antithymocyte globulin, infliximab (except in patients with HF), mycophenolate mofetil, or abatacept, should be considered (LOE, IV; GOR, C) | 8.4. Continuing approval without change |
| 8.5. For patients with cardiomyopathy and/or HF, appropriate guideline-directed medical therapy and hemodynamic support should be provided as indicated (LOE, IV; GOR, C) | 8.5. Continuing approval without change |
| 8.6. For patients with atrial or ventricular tachyarrhythmia or heart block, appropriate medical and supportive care should be provided as indicated (LOE, IV; GOR, C) | 8.6. Continuing approval without change |
| 8.7. ICI therapy should be permanently discontinued with any clinical myocarditis; the decision regarding restarting ICI therapy in the absence of alternative available antineoplastic therapy needs to be individualized with multidisciplinary discussion considering the cancer status, response to prior therapy, severity of cardiotoxicity, regression of toxicity with immunosuppressive therapy, and patient preference after weighing the risks and benefits; if ICI therapy needs to be restarted, monotherapy with an antiprogrammed cell death protein 1 (anti-PD-1) agent might be considered with very close surveillance for cardiotoxicity development (LOE, V; GOR, C) | 8.7. Continuing approval without change |
| Level of evidence (LOE) |
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| Grading of recommendation (GOR) |
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Abbreviations: CV, cardiovascular; ESMO, European Society of Medical Oncology; FDA, US Food and Drug Administration; HF, heart failure; ICOS, International Cardio-Oncology Society; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; MRI, magnetic resonance imaging; T-DM1, trastuzumab emtansine. Modified from Rogado J, Obispo B, Pangua C, et al. Covid-19 transmission, outcome and associated risk factors in cancer patients at the first month of the pandemic in a Spanish hospital in Madrid. Clin Transl Oncol. Published online May 25, 2020.27