Safe performance of echocardiography during the COVID-19 pandemic: a practical guide

or through close contact with infected people or surfaces, healthcare workers are further exposed to COVID-19. Particularly, echocardiography remains an essential diagnostic service which, due to the close contact with patients during the exam, provides echocardiographers high-risk of contagion. There-fore, the common modalities of performing echocardiography should be improved in this scenario, avoiding performing unnecessary exams, using the appropriate personal protective equipment depending on patients' status and location, optimizing time-effectiveness of the echocardiographic study and accurately sanitizing the environment and devices after each exam. This paper aims to provide a simple guide for the clinicians to balance between providing the best care to each patient and protect-ing themselves and other patients from the spread of the virus. It also proposes the use of the mnemonic PREVENT to resume the crucial indications to be followed for the execution of appropriate echocardiographic examination during the COVID-19 pandemic.


Introduction
Coronavirus disease-2019  pandemic is a worldwide public health burden, being associated with high morbidity and mortality risks, especially for specific groups of popula-tion: elderly, chronically ill, immunocompromised and pregnant women (Huang et al., 2020). Moreover, it is affecting the global provision of healthcare services. Coronavirus spreads easily from symptomatic or asymptomatic patients through direct contact and respiratory droplets associating cough or sneezes (Wu and Mc-Googan, 2020). Echocardiography is a routinely requested investigation in patients with unexplained breathlessness, particularly those with underlying cardiac conditions. The procedure is usually performed through close contact with patients, hence resulting in high contagious atmosphere. Patients with suspected or confirmed COVID-19 could fall in the category of those requiring echocardiographic assessment, a clinical need that puts the cardiologist/echocardiographer at a significant risk of catching severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection. Thus, it is of paramount importance to scrutinize the use of echocardiography during the current COVID-19 pandemic in an attempt to protect healthcare professionals, their relatives (Adams and Walls, 2020) and also other patients, both for their own health benefit as well as for controlling the spread of the disease (Conticini et al., 2020). In addition to rationalizing the use of such popular investigation, echocardiography should be provided using the appropriate personal protective equipment (PPE).
This document aims to assist clinicians in recognizing the priority indications for echocardiographic examination and optimum required precautions during the COVID-19 outbreak, proposing the use of the acronym ''PREVENT'' (Fig. 1) to easily remember the pivotal steps for a conscious use of echocardiography in this emergency scenario.

Before the exam
Transthoracic echocardiography (TTE) is commonly requested as a routine investigation in large cardiac centers and general Figure 1. Indications for the appropriate use of echocardiography to PREVENT the spread of COVID-19. COVID-19, coronavirus disease-19; ICU, intensive care unit; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography hospitals, where cardiac units of significant size, with enough echocardiographic apparatuses, provides routine daily service to other medical specialties. However, considering the high risk of catching COVID-19 from any patient, it is advisable that only necessary examinations should be undertaken, particularly in patients with unknown COVID status (Kirkpatrick et al., 2020). Patient COVID-19 status must be assessed according to local protocols. Screening for infection should be undertaken in outpatients' settings (body temperature measurement and the presence/absence of respiratory symptoms, i.e. cough, cold, flu, dyspnea over the prior 14 days) at the hospital/clinic entrance. As for hospitalization, all patients with suspected COVID-19 should undergo nasal and/or pharyngeal swab for the detection of SARS/CoV2/Nucleic Acid before admission.
Accordingly, the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) recommend that each elective echocardiogram should be postponed, regardless of patients' COVID status (non-suspected, suspected or confirmed infection) (Kirkpatrick et al., 2020;Skulstad et al., 2020). Nevertheless, primary cardiac symptoms and underlying cardiovascular disease should be recognized in a timely fashion, since they could often carry higher mortality than COVID-19 itself. In general, Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) recommends cardiologists to preserve the chance to distinguish between urgent and undeferrable TTE exams and inappropriate requests at their personal judgement (Antonini-Canterin et al., 2020). However, as a reference guide, in Table 1 we suggest a list of the most common clinical conditions which could represent Right indications to echocardiography during COVID-19 pandemic.
The key points for optimum management of TTE service during COVID-19 pandemic are: i. An initial screening of the indication, following Table 1 or general appropriateness criteria for the use of TTE in adults (Chambers et al., 2017). ii. TTE services should not be offered if unlikely to provide prompt clinical benefit to patients, which entails the prioritizing and guiding towards adequate short-term management (Wu and McGoogan, 2020). iii. Identifying urgency or emergency indications for TTE and deferring all others or define them as ''elective'' studies and reschedule them (Wu and McGoogan, 2020). iv. Prefer alternative forms for distance-consulting, with network evaluation of echocardiographic images or telemedicine, Routine echocardiographic evaluation in asymptomatic patients with underlying cardiac disease -Syncope -Chest pain -Dyspnea at rest -New cardiac murmur (concomitant dental abscess or pain?)

Chest pain in previous CAD or known CCS, with negative troponin
Uncontrolled blood pressure levels (< 200/120 mmHg) in hypertensive patients

High suspect of infective endocarditis
Cardiologic follow up of asymptomatic oncologic patients and without known or suspect CTRCD Signs and symptoms of congestive acute HF*

Low-intermediate risk NSTEMI (for prioritization to PCI)
STEMI or high risk NSTEMI (if patient is nearly going invasive coronary angiography)

Malignant arrhythmias
Dyspnea with low BNP blood levels

Suspected STEMI complications
Study of symptomatic CCS if coronary CT is available (Skulstad et al., 2020) Hemodynamic instability Routine follow up of prosthetic valves in asymptomatic or with mild-symptoms patients ICU*-> suspected acute HF Lancellotti et al., 2015) TOE for diagnostic workup or elective surgical treatment of VHD High-PEEP ventilation (Franchi et al., 2013) Veno-venous ECMO * Lung ultrasound could aid diagnosis (Gargani et al., 2020). BNP, brain natriuretic peptide; CAD, coronary artery disease; CCS, chronic coronary syndromes; CT, computed tomography; CTRCD, chemotherapy-related cardiac disease; HF, heart failure; ICU, intensive care unit; NSTEMI, non-STelevation myocardial infarction; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; PEEP, positive end-expiratory pressure; STEMI, ST-elevation myocardial infarction; TOE, transoesophageal echocardiography; VHD, valvular heart disease in order to limit patient-operator contact (Driggin et al., 2020). v. Repeated TTE should not be performed, except for clear changes of patients' clinical status. vi. Cardiac specific blood biomarkers, such as brain natriuretic peptide (BNP) or N-terminal-proBNP and cardiac troponin, could be assessed to exclude acute cardiac injury or worsening chronic heart failure, in an attempt to reduce the number of unnecessary TTEs. However, the possible interference of SARS-CoV2 with cardiac biomarkers should be considered, since it has shown to provoke an increase of troponin and BNP levels parallel to the worsening severity of the respiratory disease (Chen et al., 2020;Lippi et al., 2020).

Performing the exam
Given that the patient's indication to undergo rest or stress TTE is appropriate, the environment and the modalities of execution are crucial elements for overall personnel safety during the COVID-19 outbreak.
First of all, the operator should use the appropriate Equipment, according to local standards, which is recommended for the prevention of virus spread. Echocardiographers dealing with suspected or known COVID-19 patients may have different levels of personal protective equipment (PPE), depending on the Venue where TTE should be performed (Kirkpatrick et al., 2020): i. Droplets precautions: gown, gloves, headcover, facemask (filtering face piece particulate class 2 (FFP2), class 3 (FFP3), N95 or N99 respirators masks) and eye shield for outpatients in echo-labs or inpatients in hospital wards or emergency department; patients should wear at least surgical mask as well. ii. Airborne precautions: gown, gloves, headcover, eye shield, with special facemask (i.e. FFP2, FFP3, N95 or N99 respira-tors masks, or powered air purifying respirator (PAPR) systems) and shoe covers for patients hospitalized in intensive care units, or ventilated patients treated with invasive/noninvasive oxygen therapy.
In case of NON-suspected or known COVID-19 patient, TTE could regularly be performed in echo-labs or hospital wards, according to the new world health organization (WHO) recommendations, which states that only patients undergoing aerosolgenerating procedures require airborne isolation (World Health Organization, 2020a). Nevertheless, standard precautions are essential, i.e. frequent and meticulous handwashing, use of gloves and surgical masks; patients wearing surgical mask.
Given the above, it is fundamental to ensure the education of healthcare professionals on the correct methods of dressing/undressing. WHO (World Health Organization, 2020b) specific document reports detailed information about the rational use of PPE for COVID-19 prevention.
It is important to Expedite the duration of TTE examination, limiting its use to answer the clinical question, since prolonged scanning could expose the operator to increased risk of infection (Kirkpatrick et al., 2020;Skulstad et al., 2020). Therefore, echocardiographic exams in patients with suspected or confirmed COVID-19 should be: i. focused to the indication question and prepared in advance based on findings of previous examination and cardiac condition details. ii. on the other hand, TTE should be comprehensive enough to avoid the need for repeat examination or other investigations; iii. performed by experienced operators (not students or intraining practitioners) in order to optimize the time/quality ratio of images acquisition; iv. ultrasound enhancing agent (contrast) use should be planned in advance, so as to prevent the unnecessary waiting time or/and the need for personal potential contamination of other areas while preparing the contrast. v. Advanced analyses or measures, such as speckle tracking echocardiography , should not be overlooked if they could provide relevant additional information for the clinical question, however, they should be carefully performed offline in a safe environment, using TTE images acquired and saved in a storage driver. Some authors suggest that portable echocardiographs could be used to perform TTE in suspected or known COVID-19 subjects in order to avoid SARS-CoV2 transmission throughout the hospital while moving them, and for their much easier cleaning procedures (Kirkpatrick et al., 2020;Skulstad et al., 2020;World Health Organization, 2020b). However, usually COVID-19 patients are isolated in dedicated units, and the capability of the virus to remain active on surfaces for several days should be considered (Kampf et al., 2020;van Doremalen et al., 2020). Hence, perhaps the best option is the use of a unique device in infected areas by a dedicated echocardiographer who follows optimum hygiene recommendations (Antonini-Canterin et al., 2020) and avoiding carrying unnecessary objects e.g. electrodes for ECG trace, additional probes.
Alternatively, special protocols known as ''point-of-care ultrasound (POCUS)'' (Kirkpatrick et al., 2020) or ''FocUS'' (Neskovic et al., 2018), performed by trained clinicians by handheld devices, can play a role in optimizing TTE evaluation at referral to the emergency department or for repeated evaluations in critical patients, to obtain a rapid assessment of biventricular function, valvular disease, pericardial and pleural effusion (Lisi et al., 2012). This approach could be useful to screen for cardiac contributions to symptoms or signs during COVID-19 infection or to identify patients who need complete echocardiographic examination, avoiding the exposure of other clinicians to SARS-CoV2 . In doubtful cases, images obtained by POCUS can be archived to allow remote visualization or future review from more experienced echocardiographers for interpretative consulting or comparisons of cardiac structure and function over time.

After the exam (Sanitize)
Noteworthy, Neatness of the room and devices is crucial to prevent COVID-19 contagion. Therefore, after TTE exam, accurate sanitization of all the equipment is recommended (British Society of Echocardiography , 2020). SARS-CoV-2 has shown to be sensitive to most standard viricidal disinfectant solutions (van Doremalen et al., 2020). WHO suggested that accurate cleaning of the environmental surfaces with water and detergents, followed by the application of disinfectant commonly used within hospital (i.e. ethanol 62-71%, sodium hypochlorite 0.1-0.5% or hydrogen peroxide 0.5%) would be sufficient (Kampf et al., 2020).
According to the variety of local standards, it is important to ensure a thorough cleaning of echocardiograph and probes early after using them, while providing room ventilation. Wet swabs with 70% alcoholic solution for the echocardiographs, and ammonium quaternarium for the probes, could be used (Skulstad et al., 2020). Nonetheless, cleaning procedures could also vary among vendors, thus it is advisable to adhere to individual vendors disinfecting guidelines.
Lastly, the staff participation should be limited to the ones performing TTE exam, avoiding people gatherings to review or discuss TTE findings. If necessary, remote images review and clinical consultation via telephone or web-networks are recommended.

Transoesophageal echocardiography (TOE)
TOE is characterized by very high risk of SARS-CoV-2 transmission, since it can cause aerosolization of a large amount of virus.
Therefore, the recommendations for TOE performance are quite different than those for TTE (Kirkpatrick et al., 2020): i. TOE should be postponed or cancelled unless urgent, if it is unlikely to change clinical care, and/or if alternative TTE (e.g. off-axis TTE views, use of ultrasound enhancing agents) could be sufficient to obtain the necessary information.
Obviously, further care than usual should be provided during the disinfection of the echocardiograph and the probe after TOE, according to vendors' specific guidelines.

Use of echocardiography to study MIS-C
Among the most worrisome complications of COVID-19, Multisystemic Inflammatory Syndrome in Children (MIS-C) has recently been discussed by pediatricians, rheumatologist and cardiologist communities (Sinha et al., 2020). This is probably caused by an acute severe cytokine storm and resembles toxic shock syndrome and atypical Kawasaki disease (KD). It frequently leads to acute heart failure and cardiogenic shock often representing the first manifestation of COVID-19 in children and adolescent, requiring inotropes and cardiac mechanical assistance (Belhadjer et al., 2020). To date, more than 200 patients with MIS-C with temporal association with COVID-19 have been reported.
According to the newest studies on patients with MIS-C, electrocardiograms could be non-specific, while echocardiography show the same imaging findings of patients with KD (McCrindle and Cifra, 2017;Riphagen et al., 2020;Verdoni et al., 2020). Therefore, we hypothesize that TTE would be useful not only for diagnosis of MIS-C, but also for prognostic assessment and follow up in case of coronary aneurysms, similarly to KD (Belhadjer et al., 2020).
The focusing points of a TTE study in suspected MIS-C are the following: • Study of LV regional and global function, calculation of ejection fraction (often reduced, with possible recovery after intravenous immunoglobulin and steroids therapy); • Dedicated views for the study of coronary arteries (McCrindle and Cifra, 2017) to assess dilatation (with Z-score > 2 (Sosa et al., 2019) based on body surface area) or echo-brightness; • Evaluation of pericardial effusion; • Detection of unknown valvular regurgitation (above all mitral regurgitation).
TTE is the first line imaging method to use in patients with MIS-C. In patients with coronary aneurysms, the risk assessment for myocardial ischemia becomes pivotal. Serial exercise (preferable) or pharmacological stress echocardiography could provide further risk stratification (sensitivity 94.4% and specificity 82.5% at beginning, 93.7% and 95.4% respectively at 15-years follow up) (Noto et al., 2013). Non-invasive imaging methods are recommended as alternatives to coronary angiograms. Coronary computed tomography scan may have a role for its high anatomic resolution and accuracy in identifying coronary stenosis and thrombi, however, it should be limited to high-risk cases due to radiation exposure; cardiac magnetic resonance would be useful to avoid radiations, but has the pitfalls to be time-consuming and less available (Tsuda and Singhal, 2017). Moreover, in COVID-19 times the use of these imaging methods should be optimized in favor of the protection of healthcare personnel and hospital environment.

Conclusions
COVID-19 outbreak exposes healthcare professionals to high infective risk with subsequent high morbidity and mortality rates, hence there is the need to reconsider the common indications and best appropriate modalities for optimum service. An optimization of TTE performance and the careful use of PPE is required, in order to ensure the adequate protection to healthcare professionals, other patients and overall surrounding environment, without compromising healthcare services provision. Following the recent evidence about COVID-19 and the recommendations of international societies of echocardiography, this document provides a set of basic suggestions to observe when performing TTE at the time of COVID-19 pandemic. Accordingly, we propose the clinicians to bear in mind the acronym PREVENT, which resumes the key indications to perform a safer echocardiographic exam, reducing the risk of COVID-19 contagion (Fig. 1).