Stress tests are essential in the evaluation of patients with suspected or confirmed coronary heart disease. They include exercise or pharmacological stress tests with any of the nuclear cardiology imaging modalities (single-photon emission computed tomography/positron emission tomography [SPECT/PET]), echocardiography, or cardiovascular magnetic resonance imaging (CMR). However, stress tests can increase the risk of contamination by droplets and should be deferred (for patients at low risk for COVID-19) or cancelled (for patients with suspected or confirmed COVID-19). Pharmacological stress should have preference over exercise. Once the pandemic fades, when clinically appropriate, exercise stress tests should include additional precautions, such as:¹

Among all the echocardiography modalities, TEE is probably the one with the highest risk of health care team contamination due to the handling of the patient's airways, contact with fluids, close contact between the patient's mouth and the professional, and to the cough reflex that can happen during the probe passage towards the esophagus. Indications for this test should thus be carefully evaluated, and the highest precaution level is recommended (even for tests performed in the operating room or in patients that do not have suspected or confirmed COVID-19)^2,3,8,12,13 (see Table 2). Ideally, TEE should be performed in an exclusive room containing protective covers for the echocardiography equipment (isolation or waterproof covering) and for all the necessary equipment, in addition to a strict and lengthy disinfection protocol for environmental surfaces between each test (approximately 1 hour).

Considering that children have a higher possibility of being infected with COVID-19 and be asymptomatic or show minimum symptoms, the triage measures that apply to adult patients can be insufficient, requiring adjustments in outpatient or inpatient echocardiography. In case of an active and cooperative patient, the echocardiography physician should preferably be the only person in contact with the child. Children under 2 years old have difficulties wearing masks, which leads to a higher risk of exposure to the virus. In addition to the main form of transmission of SARS-CoV-2 (through respiratory droplets), transmission through fomites has been assumed plausible.¹⁴ Therefore, diaper changes should be avoided, if possible, during the examination and if necessary, performed with adequate hygiene. Due to the higher risk of an asymptomatic form of COVID-19 in children, some facilities located in endemic regions choose to test new pediatric hospital admissions for SARS-CoV-2.

In facilities where fetal echocardiography (FE) is performed within the cardiology sector, pregnant women should be separated from pediatric patients, both in waiting and procedure rooms. Differently from previous viral outbreaks (H1N1, SARS-CoV, MERS-CoV), which were associated to severe complications in pregnant women, current information (although limited) suggests that these patients are not more susceptible to SARS-CoV-2 infections or, if infected, are not more prone to developing severe complications.¹⁵ However, given the uncertainty and possibility of an increase in risk as new data become available, the CDC alerts that pregnant women should protect themselves. Up to one accompanying person is allowed; for reducing exposure, the echocardiography room should ideally be occupied only by the pregnant patient and the examining physician.

Even in patients at low risk for COVID-19, the reintroduction of outpatient examinations should be progressive, considering priority criteria and the phase of the pandemic (see Table 1).^10,11,13 Next, we describe indications for each priority level.

From a cardiovascular point of view, patients affected by SARS-CoV-2 can display evidence of myocardial dysfunction (both left and right), vascular alterations, arrhythmias, thromboembolic phenomena, and pericardial effusion.⁴

Therefore, echocardiography can also contribute to the clinical assessment of patients with COVID-19, in the following situations:^2,3,17–20

In difficult acoustic windows, the use of an echocardiographic contrast agent can be employed to ensure test results, reduce test duration, and avoid inadequate diagnosis or other unnecessary tests.^21,22

In patients with COVID-19, the examination should be focused on the clinical question. Serial echocardiography should be avoided unless there is clear change in the clinical state (hemodynamic instability). However, in the ICU, the echocardiogram is frequently used for monitoring the progression of critically ill patients, especially regarding fluid management. In this case, a focused ultrasound or focused echocardiography can be used. Protocols for these cases are described below.

In patients at low risk for COVID-19, with proper indication and when deferring is not possible or recommended (such as in preoperative cancer patients or those with a high pre-test probability of obstructive coronary artery disease [CAD]), pharmacological stress tests are preferred because they are not considered aerosol-generating. Another alternative for investigating selected cases of chronic coronary arterial disease during the pandemic is to prioritize computed tomography (CT) coronary angiography.¹⁰ Once a very low local prevalence of COVID-19 is reached, exercise echocardiography can return to being the first choice, but with additional safety procedures as previously described.

TEE causes additional concern, since the risk of equipment and professional contamination through droplets and aerosols is very high. Therefore, the incremental value of TEE in relation to transthoracic echocardiography (TTE) should be carefully evaluated on a case-by-case basis together with the assistant physician. For the duration of the pandemic, alternative methods should preferably be chosen, especially in patients with COVID-19.^2,12 One of the main indications for TEE — screening for intracavitary thrombi — can be performed through CT angiography, which presents a lower risk of staff contamination. This alternative is obviously only available for patients who can be transported and with preserved renal function. Whenever possible, complete diagnosis should be achieved through TTE, leaving TEE for critical situations with possible changes in management, especially in the ICU or operation room where no other methods are available and the clinical question should be promptly answered. In areas where the pandemic is decreasing, the reintroduction of TEE for outpatients should follow strict criteria, and each case should require an individual evaluation. It is recommended that outpatient scheduling be restored based on patient priority, considering one's previous position on the waiting list, clinical indications and conditions (symptomatic or asymptomatic), and potential impact of the examination in the patient's clinical history (for example, tests required for further procedure scheduling).^2,12,13 Additional measures for TEE scheduling and test safety are described in Table 2. Among the various indications for TEE, high priority is given to the following:³²

TEE is not recommended in the following cases:

Within the pediatric age group and considering patients with congenital heart defects, absolute indications include suspected congenital heart defect, postoperative and preoperative evaluation of congenital heart defects, children with acquired heart disease, heart transplant, increased risk of impaired cardiac function (chemotherapy treatment), and cardiac complications associated with respiratory infections.^33,34 These indications should be categorized as high, medium, or low priority, as demonstrated in Table 2, when reintroducing examinations at the outpatient level according to the hemodynamic repercussions and clinical reasoning.

TTE should be performed in the usual manner due to the wide anatomical variability and challenges regarding the evaluation of systolic and diastolic function, thus leaving focused assessment for other applications such as the emergency sector, pediatric intensive care, and in suspected of confirmed COVID-19 patients. In case of a potentially complicated examination, the patient should be referred to a more experienced physician; this increases the probability of an adequately detailed, precise, and quick examination without the need for additional practical support. Recently, an alert regarding multisystem inflammatory syndrome in children and teenagers has been released; this disorder has been described as a generally late clinical presentation associated with COVID-19, characterized by similar manifestations to those of the typical or incomplete Kawasaki syndrome and/or septic shock syndrome.³⁵ The most affected age range includes school-age children (mean age 9 years), which differentiates this disorder from the Kawasaki syndrome; symptoms are predominantly gastrointestinal. Virtually 100% of cases have heart affections with LVEF impairment, which has been described by various groups. In addition, patients present cardiogenic shock and coronary artery involvement with variable degrees of dilation, and some groups have reported aneurysms. Respiratory symptoms are mild, and skin rash and mucosal involvement may also occur.^35,36 In case of clinical suspicion of multisystem inflammatory syndrome in children and teenagers, the main objectives of echocardiography are to identify possible left ventricular dilation, measure systolic function through LVEF, quantify the valvular regurgitation, evaluate the morphological aspect of coronary arteries (dilation and/or aneurysm), and pericardium.

FE assessment faces challenges in the final stage of pregnancy where perinatal and neonatal planning and decision-making are required. At first, patients with low-risk pregnancies were instructed to not perform FE; those with moderate-risk pregnancies should defer FE for when the COVID-19 risk was reduced or until 28 weeks of pregnancy; finally, women with high-risk pregnancies should promptly schedule and perform the examination.¹⁵ However, as the pandemic progressed, considering that pregnancies would continue and fetal cardiac diseases can be critical, we recommend that FE be performed according to the previously published guidelines.^37,38 The examination should be performed following PPE protocols for the pregnant patient and health care professional. Echocardiographic assessment should be as complete as possible, avoiding re-evaluations.

The possibility of prenatal or perinatal infection should be considered when newborns are transferred to the pediatric or cardiac neonatal intensive care unit after birth. Data on the vertical transmission of SARS-CoV-2 are still scarce;^39,40 however, if the new mother tests positive for the virus in the 14 days after birth, the newborn should also be tested and managed as a positive case until a negative result is confirmed.

Echocardiographic tests in the pediatric population and in patients with congenital heart defects remain crucial during the SARS-CoV-2 pandemic and their health care should be guaranteed, minimizing risks for the professional team, patients, and the general public.

In patients with congenital heart defects, TEE is considered a part of intraoperative care and hemodynamic interventions. In outpatient cases, considering the high risk of exposure to SARS-CoV-2, this examination should be deferred or substituted for an alternative modality such as TTE associated with agitated saline contrast, cardiovascular computed tomography (CCT) or CMR with contrast agents. As for children, the risks and benefits of aerosol-emitting procedures should be weighed along with those of patient transportation, disinfection of the CCT/CMR room, contrast administration or radiation in CCT, in addition to prolonged exposure in case of CMR.

Due to the unreliability of using symptoms in the prediction of COVID-19 status in children, a specific recommendation has been proposed for TEE in these patients:¹⁵

Considering outpatients without COVID-19, the types of examinations should be categorized according to indication priority (see Table 1). High-priority (essential) examinations include venous VUS for DVT screening, as well as the carotid and vertebral artery VUS in patients with suspected stroke. Considering patients with peripheral obstructive disease, a priority for arterial VUS should depend on surgical treatment indications.

Other examinations should be categorized as medium or low priority by the assistant physician, as long as there are no indications for urgent invasive treatments. These include VUS of the aorta and its branches, VUS for varicose vein assessment, and carotid artery VUS in screening for carotid artery disease in the preoperative period of cardiac surgery.

Venous VUS should not be used as a marker for altering a patient's anticoagulant therapy management.

Laboratory tests cannot indicate the need for this examination; hence, high D-dimer values do not justify VUS for DVT screening. In case of negative D-dimer results, there is no need for VUS in DVT screening.

Upper limb DVT has low morbidity in critically ill patients, thus there is no routine recommendation for venous VUS in this region.

In conclusion, VUS is not recommended in situations where its results will not determine changes in management or are not a prerequisite for urgent surgery.

The complete venous VUS protocol is the recommended method for investigating DVT; however, point-of-care 3- or 2-point compression ultrasound in critically ill inpatients with COVID-19 seems to be a reasonable option, except if the pain reported by the patient is located in the infrapatellar segment (then, the complete protocol should be performed). The 3-point protocol assesses compressibility in all proximal veins of the evaluated lower limb. The 2-point protocol evaluates the compressibility of the common femoral vein 1 to 2 cm above and below the saphenofemoral junction (in the inguinal fold) and in the popliteal vein up to the confluence of the leg veins.⁴² Total or partial absence of compressibility in the affected vein, as well as vascular swelling due to an intraluminal thrombus detected by 2-dimensional techniques, are ultrasonographic signs of DVT. The sensitivity of the 3-point compression method is considered greater than that of the 2-point method (90.57% vs 82.76%), with similar specificity (98.52%).⁴³

In addition to a shorter exposure period for the professional, the point-of-care VUS protocol can be performed by the emergency physician, provided proper training is involved. After the pandemic, when possible, the complete protocol should be given preference.

Other VUS examinations, such as the carotid and vertebral artery VUS and limb arterial VUS, when necessary, should follow previously established protocols.⁴⁴ All protective and PPE measures should be followed as previously discussed.

The COVID-19 pandemic caused an important reduction in the number of outpatient requests for CMR, leaving only high-priority examinations: Clinical suspicion of myocarditis, differential diagnosis of cardiac masses, as well as other exceptional situations such as the assessment of complex ventricular arrhythmias.

CMR is well-defined as the preferred method for the reliable assessment of ventricular function, cardiac volumes, ischemia, myocardial viability, as well as in the detection of areas of myocardial fibrosis, study of infiltrative and deposition diseases, structural evaluation of patients with cardiac arrhythmias, and in specific cases, for complementing the echocardiographic evaluation of valvular and congenital heart diseases. In patients with low risk for COVID-19, prioritization should follow the rationale presented in Table 1. CMR has the advantage of providing, with one test, a global assessment of the heart with multiple functional and structural data, thus avoiding multiple trips to the hospital or clinic; this reduces patient circulation and optimizes resources.⁴⁵ In patients with COVID-19, CMR allows the diagnostic of myocarditis, perimyocarditis, acute myocardial infarction with no evidence of obstructive coronary artery disease (MINOCA), Takotsubo syndrome, and the differentiation between ischemic and inflammatory presentations. Conversely, the patient's risk of transmission and instability in the acute phase should be carefully evaluated and the examination could be deferred, whenever possible, until the criteria for cure are attained. On the other hand, a recent study evaluated myocardial injury in patients who had recovered from COVID-19 and showed a high prevalence of nonischemic delayed myocardial enhancement and preserved systolic function, already with no evidence of edema, suggesting permanent myocardial damage.⁴⁶ CMR can thus be an important tool for better comprehending the mechanisms of myocardial injury and for assessing myocardial damage after recovery from COVID-19.

CMR protocols should be reduced (maximum 30 minutes) for all clinical indications; the focus should be on evaluating myocardial function through cine magnetic resonance imaging (MRI), while myocardial tissue characterization should be performed through late gadolinium enhancement. A T2 weighted anatomical sequence can be performed for detecting myocardial edema in case of suspected acute myocardial inflammation. When available, T1, T2, and/or T2* mapping associated with cine MRI sequences and late enhancement constitute an optimized and efficient protocol.¹¹ When evaluating myocardial ischemia, the physician should focus on perfusion sequences under pharmacological stress, subsequently adding cine and late enhancement sequences after stress. CMR can also be employed in the diagnosis of intracavitary thrombi, with a fast and directed study using late gadolinium enhancement and avoiding the need for TEE, thus reducing the examining physician's exposure to potential contamination. The evaluation of cardiac masses is adequately performed with high sensibility using CMR and can identify benign or malignant characteristics; it is though quite limited in the diagnostic of vegetations due to their small dimensions and mobile characteristics. Mass characterization should follow the routine protocol, which uses cine MRI sequences, T1 weighted anatomical sequences with or without fat suppression, T2, rest perfusion, and late enhancement, always focused on mass localization. Congenital diseases can have optimized assessment with the use of 3D resonance angiography associated with cine MRI sequences, and in case valve assessment is needed for complementing the echocardiography, ventricular function assessment through cine MRI should be prioritized and protocols should be directed to the valvular apparatus with flow mapping sequences.⁴⁷

CCT can be used in the evaluation of multiple forms of heart diseases in all stages of the COVID-19 pandemic in a fast, efficient, and safe manner.⁴⁸ For this, depending on the local stage of the pandemic, the risk of exposure to the virus in the examination should be weighed with the benefit of its results for patient management and treatment.¹¹ Table 3 proposes the prioritization of indications during the COVID-19 pandemic.

As for indications, the main diagnostic and prognostic characteristics of CCT should be taken into consideration when making a decision:⁴⁹

Nuclear cardiology has a superior role in the pandemic scenario considering patients without COVID-19. The rationale for prioritizing examinations should be as described in Table 2. The main indications include:¹¹

On the other hand, a nuclear cardiology assessment is generally not necessary in the treatment of acute heart disease in patients with COVID-19. Ventilation scans or exercise stress tests should be omitted in areas going through the peak phase of the pandemic and/or in any patient with a known or suspected COVID-19 infection due to the high risk of aerosol emission.⁵² Specific considerations on the ventilation/perfusion scintigraphy protocol are described below.

Currently, the gold standard for ruling out PE in patients with COVID-19 is the CT pulmonary angiography. However, this method cannot be used in patients with contraindications for iodinated contrast agents. A potential alternative relies in lung perfusion single-photon emission computed tomography (SPECT) using macroaggregated albumin tagged with ^99mTc. Due to the high risk of aerosol production associated to ventilation scintigraphy (aerosols tagged with ⁹⁹mTc), the American Society of Nuclear Medicine and Molecular Imaging discouraged the classical combination of ventilation/perfusion images in patients with COVID-19.⁵³ Ventilation scans should be omitted in patients with known or suspected COVID-19; therefore, the use of perfusion lung scintigraphy associated with chest CT or X-ray has been proposed.⁵⁴

For optimizing protocols amidst the pandemic, one should follow good imaging practices that allow for a safe and efficient examination, as already described; these include mainly:

Figure 5 is a proposition that summarizes the general protocol for reintroducing cardiovascular imaging examinations. Firstly, it is necessary to define whether the test is essential at any given moment. If it is essential (urgent or high-priority), define whether the patient has a high risk for COVID-19 and which method would lead to the lowest risk of exposure, even with the use of PPE. In case the examination is not essential/urgent, evaluate the local stage of the pandemic: when the area is at the peak stage, defer lower priority examinations. If the pandemic is decelerating in the area in question, reintroduce test scheduling according to the patient's risk for COVID-19 and indication priority, within appropriate criteria; finally, define PPE and patient flow according to COVID-19 risk and type of test. Tables 1, 2, and 3 summarize the indication prioritization, safety protocols, and PPE to be used according to the type of test and COVID-19 status. Among cardiovascular imaging examinations, echocardiography is considered first-line. However, in view of the need for minimizing the examining physician's exposure to SARS-COV-2 and rationally using available resources, alternative methods can be used to answer the clinical question, especially in stable patients or those with uncertain symptoms or who were referred to other imaging examinations.⁸