The Role of Hand-Held Cardiac Ultrasound in Patients with COVID-19

The role of point-of-care ultrasound (POCUS) in patient management has been established in recent years as an important tool. It is increasingly used by multiple medical disciplines in numerous clinical settings, for different applications and diagnostic purposes and in the guidance of procedures. The introduction of small-sized and inexpensive hand-held ultrasound devices (HUDs) has addressed some of the POCUS-related challenges and has thus extended POCUS’ applicability. HUD utilization is even more relevant in the COVID-19 setting given the operators’ infection risk, excessive workload concerns and general equipment contamination. This review focuses on the available technology, usefulness, feasibility and clinical applications of HUD for echocardiogram assessment in patients with COVID-19.


Introduction
Cardiovascular disease is a well-established risk factor for morbidity and mortality among hospitalized coronavirus disease 2019 (COVID-19) patients, with worse outcomes among COVID-19 patients with abnormal echocardiography results [1,2]. Furthermore, it has been demonstrated that elevation in cardiac biomarkers, e.g., high-sensitivity cardiac troponin-I, is associated with a poor prognosis in COVID-19 patients [3]. Accordingly, echocardiography is an important tool in the clinical management of patients hospitalized with COVID-19 [4]. However, the routine echocardiographic assessment of COVID-19 patients is currently discouraged due to the risk of infection of echocardiography professional operators, concerns of excessive workload and general equipment contamination in the setting of the pandemic [5][6][7]. In this setting, hand-held ultrasound device (HUD) can be utilized as an instantaneous clinical diagnostic tool that minimizes clinician-patient interaction. This review focuses on the available technology, usefulness, feasibility and clinical applications of HUD for echocardiography in patients hospitalized with COVID-19.

The Rational of HUD-Based Cardiac POCUS Utilization in COVID-19 Setting
Point-of-care ultrasound (POCUS) in the practice of different medical disciplines continues to evolve with a recognition of its role as a valuable adjunct to the delivery of excellent clinical care [8,9]. POCUS is utilized for many clinical applications, including resuscitative, diagnostic, procedural, therapeutic and monitoring [10]. POCUS has numerous benefits when compared to traditional ultrasound devices, including shortened time-to-diagnosis and treatment, reduction in use of radiation-requiring imaging studies and procedures, reduced cost, portability, dynamic and focused exam, bedside evaluations and high availability, including for follow-up examinations [11,12]. These advantages may even be more marked when it comes to HUD use [13]. These benefits have the potential to play a significant role in COVID-19 milieu, as its special setting requires evaluation,

HUDs: Probe Technology and Equipment
To allow cost reduction with fewer complexities, technologic innovations have been incorporated, replacing the traditional use of piezoelectric crystals with a novel ultrasoundon-chip technology method that incorporates a two-dimensional array of 9000 micro sensors capable of emulating different transducers over a small frequency range [18]. This technology bypasses the traditional connection necessities between the probe and a specific designated display, enabling the image to be displayed on a nonspecific mobile device, thus reducing costs and further increasing portability.
The range of HUDs have recently been introduced into practice with differing physical characteristics, probe availability, technologies, connectivity and applications. The ultrasound device transducer is the most important component of the imaging system, and the quality of the images mainly relies on its performance. Accordingly, many of the HUDs are in fact hand-held ultrasound probes that can be connected to a wide array of commercially available mobile devices. Table 2 summarizes examples of different HUDs and probes, including type and manufacturer, relevant cardiac probe, physical aspects, display platforms (designated partnered console vs. commercially available mobile devices) and wireless function capabilities. When it comes to choosing a device, among the considerations to be included are the following: dedicated display platform vs. mobile tablet support, cabled probe vs. cableless, dual probe (two-headed transducer), durability, prominent buttons, weight, battery life, clips quality, depth, operating band width to support multiple imaging modes, artificial intelligence-based tools, touch screen, company support availability and advanced features (3D, Doppler types, captured temporal features, etc.). considerations to be included are the following: dedicated display platform vs. mobile tablet support, cabled probe vs. cableless, dual probe (two-headed transducer), durability, prominent buttons, weight, battery life, clips quality, depth, operating band width to support multiple imaging modes, artificial intelligence-based tools, touch screen, company support availability and advanced features (3D, Doppler types, captured temporal features, etc.). considerations to be included are the following: dedicated display platform vs. mobile tablet support, cabled probe vs. cableless, dual probe (two-headed transducer), durability, prominent buttons, weight, battery life, clips quality, depth, operating band width to support multiple imaging modes, artificial intelligence-based tools, touch screen, company support availability and advanced features (3D, Doppler types, captured temporal features, etc.). tablet support, cabled probe vs. cableless, dual probe (two-headed transducer), durability, prominent buttons, weight, battery life, clips quality, depth, operating band width to support multiple imaging modes, artificial intelligence-based tools, touch screen, company support availability and advanced features (3D, Doppler types, captured temporal features, etc.). prominent buttons, weight, battery life, clips quality, depth, operating band width to support multiple imaging modes, artificial intelligence-based tools, touch screen, company support availability and advanced features (3D, Doppler types, captured temporal features, etc.). Designated console (5.7") -* Devices are arranged in an alphabetical order. A representative wired and wireless devices were chosen from each company. Technical details were taken from formal websites. The probes weight is with battery (whenever available). † Photos published with permission from the manufacturers. All rights reserved. ** Screen and probe size include the following measures: width × height × depth and length × width × depth, respectively. Abbreviations: HUD, hand-held ultrasound device; mm, millimeter; P, probe; S, screen.

POCUS Usefulness for Echocardiography Assessment in COVID-19 Patients
There are growing data supporting the utilization of POCUS for the diagnosis, evaluation and management of COVID-19 patients. Lung POCUS has a good diagnostic performance in a COVID-19 setting and can be used for COVID-19 diagnosis at patient's home for identifying respiratory complications as well as a screening tool among symptomatic patients [19]. POCUS can also be incorporated as an important tool for the cardiovascular system assessment with different available scanning protocols [20]. The American Society of Echocardiography states that POCUS examinations performed by clini- Designated console (5.7") -* Devices are arranged in an alphabetical order. A representative wired and wireless devices were chosen from each company. Technical details were taken from formal websites. The probes weight is with battery (whenever available). † Photos published with permission from the manufacturers. All rights reserved. ** Screen and probe size include the following measures: width × height × depth and length × width × depth, respectively. Abbreviations: HUD, hand-held ultrasound device; mm, millimeter; P, probe; S, screen.

POCUS Usefulness for Echocardiography Assessment in COVID-19 Patients
There are growing data supporting the utilization of POCUS for the diagnosis, evaluation and management of COVID-19 patients. Lung POCUS has a good diagnostic performance in a COVID-19 setting and can be used for COVID-19 diagnosis at patient's home for identifying respiratory complications as well as a screening tool among symptomatic patients [19]. POCUS can also be incorporated as an important tool for the cardiovascular system assessment with different available scanning protocols [20]. The American Society of Echocardiography states that POCUS examinations performed by clini- Designated console (5.7") -* Devices are arranged in an alphabetical order. A representative wired and wireless devices were chosen from each company. Technical details were taken from formal websites. The probes weight is with battery (whenever available). † Photos published with permission from the manufacturers. All rights reserved. ** Screen and probe size include the following measures: width × height × depth and length × width × depth, respectively. Abbreviations: HUD, hand-held ultrasound device; mm, millimeter; P, probe; S, screen.

POCUS Usefulness for Echocardiography Assessment in COVID-19 Patients
There are growing data supporting the utilization of POCUS for the diagnosis, evaluation and management of COVID-19 patients. Lung POCUS has a good diagnostic performance in a COVID-19 setting and can be used for COVID-19 diagnosis at patient's home for identifying respiratory complications as well as a screening tool among symptomatic patients [19]. POCUS can also be incorporated as an important tool for the cardiovascular system assessment with different available scanning protocols [20]. The American Society of Echocardiography states that POCUS examinations performed by clinicians who are already caring for the patients present an attractive option for echocardio- Designated console (5.7") -* Devices are arranged in an alphabetical order. A representative wired and wireless devices were chosen from each company. Technical details were taken from formal websites. The probes weight is with battery (whenever available). † Photos published with permission from the manufacturers. All rights reserved. ** Screen and probe size include the following measures: width × height × depth and length × width × depth, respectively. Abbreviations: HUD, hand-held ultrasound device; mm, millimeter; P, probe; S, screen.

POCUS Usefulness for Echocardiography Assessment in COVID-19 Patients
There are growing data supporting the utilization of POCUS for the diagnosis, evaluation and management of COVID-19 patients. Lung POCUS has a good diagnostic performance in a COVID-19 setting and can be used for COVID-19 diagnosis at patient's home for identifying respiratory complications as well as a screening tool among symptomatic patients [19]. POCUS can also be incorporated as an important tool for the cardiovascular system assessment with different available scanning protocols [20]. The American Society of Echocardiography states that POCUS examinations performed by clinicians who are already caring for the patients present an attractive option for echocardiographic assessment by reducing unnecessary clinician-patient exposure [6].
The long-lasting debate as to whether diagnostic ultrasonography is superior to cardiac physical examination is even more relevant in COVID-19 clinical assessment [21]. Patient management in a COVID-19 setting involves personal protective equipment and strict infection control, measures that significantly limit the ability to perform the traditional physical examination, especially when it comes to stethoscope use [22]. It has been shown that POCUS has a higher diagnostic performance in patients with dyspnea than physical examination and stethoscopes in heart failure and pneumonia diagnosis [23]. In addition, POCUS use enables the diagnosis of cardiac entities that do not manifest as clearly as other diseases when addressed by physical examination (e.g., cardiac tamponade, pneumothorax, pulmonary embolism) [24].
Studies conducted on the POCUS-based management of patients hospitalized with COVID-19 have found a relatively high rate of cardiac abnormalities ranging up to 68%, with right ventricular (RV) systolic dysfunction being the most predominant finding (10-52.8%) [1,[25][26][27][28][29][30]. A cross-sectional study demonstrated an association between disease severity and the prevalence of abnormal echocardiography results when comparing patients with non-severe COVID-19 to those with severe disease [31]. The study demonstrated larger biventricular diameters alongside with lower left ventricular ejection fraction (LVEF) and RV fractional area change (FAC) in those with severe disease. Furthermore, an association between cardiac abnormalities on echocardiography and mortality was found for both left ventricular (LV) longitudinal strain and RV free-wall strain. These results are less applicable for routine use as strain measurement is not generally performed in POCUS-based exams [32]. Lastly, the abnormal echocardiographic findings in patients admitted with COVID-19 can lead to management change in nearly one-third of tested patients [30]. These data suggest that the use of cardiac POCUS among other imaging modalities has the potential for clinical management adjustment and prognostic value among COVID-19 patients while minimizing the risk of contamination.

HUD Feasibility and Quality for Echocardiographic Assessment in COVID-19 Patients
Cardiac POCUS using a HUD has been widely adopted as a routine diagnostic tool in critical care as well as in other settings. However, the clinical data regarding HUD use for echocardiography assessment in COVID-19 setting is limited. The majority of COVID-19 POCUS-based studies were performed with standard ultrasound machines that are full-size and mobile.
A retrospective controlled study from Connecticut investigated the feasibility of HUD use (Lumify™) for cardiac evaluation among COVID-19 patients [33]. They showed that all HUD-based examinations (n = 90) were deemed to be diagnostic and provided sufficient information for the clinical care team. Despite the high rate of intubated patients (n = 57; 63.3%), no repeated echocardiography studies were required due to the inadequate imaging of the preliminary study performed using HUD. Similarly, in a recent prospective study conducted among 103 consecutive COVID-19 patients hospitalized in designated medical wards, we demonstrated through a blinded, fellowship-trained echocardiographer that only 13% of HUD-based studies (Vscan Extend™ with the dual probe) were categorized as having poor quality (Figure 1) [34]. The quality of RV demonstration was also high, with good/fair quality in 91% of the exams. The real-time interpretative accuracy of HUD-based LVEF assessment by the operators during the exam acquisition was reliable with fair to good correlation (r = 0.679, p < 0.001) and substantial agreement (Kappa = 0.612, p < 0.001) between the operator and the gold standard ( Figure 2) [34]. The quality of RV demonstration was also high, with good/fair quality in 91% of the exams. The real-time interpretative accuracy of HUD-based LVEF assessment by the operators during the exam acquisition was reliable with fair to good correlation (r = 0.679, p < 0.001) and substantial agreement (Kappa = 0.612, p < 0.001) between the operator and the gold standard ( Figure 2) [34].
LVEF agreement was also assessed using the Bland-Altman analysis revealing a mean bias of −0.96 (95% limits of agreement 9.43 to −11.35; p = 0.075). However, with regard to RV systolic function, only a fair agreement was demonstrated as compared with expert echocardiographer (Kappa = 0.308, p = 0.002).
In accordance with current COVID-19 guidelines recommending a shortened sonography time, the scan time using a HUD ranged from a mean of 5 ± 2 to 9 ± 3 min, a reduction of up to 79% in scanning time as compared with the conventional device controlled scan (a mean of 24 ± 7 min) [33,34]. Similarly, Maheshwarappa et al. found, in a prospective controlled observational study, a significant reduction of 55% in the scanning time using HUD device as compared with a standard device from a median of 20 (IQR of 17-22) minutes down to 9 (IQR of 8-11) minutes; p < 0.001 [35]. Furthermore, the total time duration spent in the patient's room decreased by 71% [33]. LVEF agreement was also assessed using the Bland-Altman analysis revealing a mean bias of −0.96 (95% limits of agreement 9.43 to −11.35; p = 0.075). However, with regard to RV systolic function, only a fair agreement was demonstrated as compared with expert echocardiographer (Kappa = 0.308, p = 0.002).
In accordance with current COVID-19 guidelines recommending a shortened sonography time, the scan time using a HUD ranged from a mean of 5 ± 2 to 9 ± 3 min, a reduction of up to 79% in scanning time as compared with the conventional device controlled In addition, HUD battery usage was good (14 ± 5% of battery capacity) with reasonable operator-to-patient proximity (59 ± 11 cm) leading to good perceptual measurements of operator safety [34].
Additionally, following the manufacturer-recommended protocol, the time required for disinfection decreased by 86% using a HUD as compared with conventional device [33].

The Usefulness and Diagnostic Yield of HUD for Echocardiography Assessment in COVID-19 Patients
The usefulness of HUD for echocardiographic assessment in non-COVID-19 settings was shown to be accurate for LV systolic function evaluation as compared with formal echocardiography [36,37], though concerns were raised regarding its use for valvular abnormalities assessment in case of moderate/severe pathologies or in case of valvular stenosis [38,39]. However, data regarding the usefulness of HUD for cardiac assessment in COVID-19 setting is more limited. Maheshwarappa et al. found that HUD-based cardiac assessment in COVID-19 patients was accurate and reliable when compared with conventional device assessment [35]. In a recent prospective study, we have demonstrated that COVID-19 hospitalized patients with an abnormal HUD-based echocardiogram were older and more likely to suffer from comorbidities and the use of chronic heart failure medications [40]. Additionally, HUD-based abnormal echocardiogram (defined as abnormal ventricular function/size or significant valvular pathology) was associated with worse endpoints (Figure 3).
In addition, HUD battery usage was good (14 ± 5% of battery capacity) with reasonable operator-to-patient proximity (59 ± 11 cm) leading to good perceptual measurements of operator safety [34].
Additionally, following the manufacturer-recommended protocol, the time required for disinfection decreased by 86% using a HUD as compared with conventional device [33].

The Usefulness and Diagnostic Yield of HUD for Echocardiography Assessment in COVID-19 Patients
The usefulness of HUD for echocardiographic assessment in non-COVID-19 settings was shown to be accurate for LV systolic function evaluation as compared with formal echocardiography [36,37], though concerns were raised regarding its use for valvular abnormalities assessment in case of moderate/severe pathologies or in case of valvular stenosis [38,39]. However, data regarding the usefulness of HUD for cardiac assessment in COVID-19 setting is more limited. Maheshwarappa et al. found that HUD-based cardiac assessment in COVID-19 patients was accurate and reliable when compared with conventional device assessment [35]. In a recent prospective study, we have demonstrated that COVID-19 hospitalized patients with an abnormal HUD-based echocardiogram were older and more likely to suffer from comorbidities and the use of chronic heart failure medications [40]. Additionally, HUD-based abnormal echocardiogram (defined as abnormal ventricular function/size or significant valvular pathology) was associated with worse endpoints (Figure 3).  Abnormal echocardiogram independently predicted the composite endpoint (OR 6.19; 95% CI 1.50-25.57, p = 0.012). Another important finding was that among low-risk patients (room-air oxygen saturation ≥ 94%), the prevalence of the composite endpoint was very low (3.1%) with a low positive predictive value for HUD use in this group of patients. These results indicate that the utilization of a HUD is an important "rule-out" tool among COVID-19 high-risk patients and should be integrated early into their routine evaluation. HUD can be utilized for different echocardiographic clinical applications in the setting of COVID-19 infection. Figure 4 shows examples of routine HUD-acquired echocardiographic images in COVID-19 patients. Abnormal echocardiogram independently predicted the composite endpoint (OR 6.19; 95% CI 1.50-25.57, p= 0.012). Another important finding was that among low-risk patients (room-air oxygen saturation ≥ 94%), the prevalence of the composite endpoint was very low (3.1%) with a low positive predictive value for HUD use in this group of patients. These results indicate that the utilization of a HUD is an important "rule-out" tool among COVID-19 high-risk patients and should be integrated early into their routine evaluation. HUD can be utilized for different echocardiographic clinical applications in the setting of COVID-19 infection. Figure 4 shows examples of routine HUD-acquired echocardiographic images in COVID-19 patients. There are several case reports/series describing HUD utilization in acute-care settings among COVID-19 patients for wide range of diagnoses [41][42][43][44]. A comprehensive list of HUD-based echocardiographic assessment in a COVID-19 setting, including evaluated entities, parameters and potential diagnoses, is detailed in Table 3. There are several case reports/series describing HUD utilization in acute-care settings among COVID-19 patients for wide range of diagnoses [41][42][43][44]. A comprehensive list of HUD-based echocardiographic assessment in a COVID-19 setting, including evaluated entities, parameters and potential diagnoses, is detailed in Table 3. Some of the HUDs can measure the pulsed and wave Doppler and can potentially be used for the assessment of diastolic dysfunction, tamponade reciprocal respiration-related variations and valvular semi-quantitative and quantitative assessment; however, they required prior specific training and knowledge and are less readily available for non-expert operators in COVID-19 settings. * RV free wall akinesis with the sparing of the apex (in patients with RV strain, the sign can be useful to differentiate between pulmonary hypertension and pulmonary embolism). † Shock assessment using HUD echocardiography can be based on LV functionality and size, LV ejection fraction, IVC size and collapsibility, pericardial effusion and evidence for pulmonary congestion. Abbreviations: HUD, hand-held ultrasound device; IVC, inferior vena cava; LV, left ventricle; mm, millimeter; RV, right ventricle. Different protocols were proposed for cardiac POCUS [20]. HUD-based echocardiography has a significant role in the diagnosis of COVID-19 associated abnormal processes, including hyperdynamic cardiac function, stress-induced cardiomyopathy, RV enlargement, pericardial effusion, acute pulmonary hypertension (secondary to pulmonary embolism or to the detrimental effects on the lung parenchyma) and diffuse myocardial inhibition, among other less common diagnoses. Figure 5 shows examples of abnormal findings using HUD for echocardiography real-time assessment among COVID-19 patients.

Evolving Technology and Future Perspectives
Newer designs of miniaturized HUD and wireless transducers are being evaluated, including wearable, belt-like and vascular imaging [45]. Tissue Doppler Imaging (TDI), three-dimensional (3D) and advanced technologies are mostly lacking or limited in currently available devices. With the further development of the novel ultrasound-on-chip technology, more applications would be readily available for real-time use. Additionally, the increasing repertoire of available artificial intelligence applications is expected to advance even more in coming years, including automatic indices measurements, quality grading and acquisition real-time improvement feedback [46,47]. These tools can be used as decision support tools for diagnostic accuracy improvement, acquisition optimization, multiple image interpretation integration and reduction in variability. Many of these applications are mainly relevant for non-expert operators. Moreover, the combination of image digitalization and tele-robotics may expand the use of ultrasound even further, enabling experts to perform an examination from a distance, thus virtualizing both interpretation and ultrasound image acquisition via semi-autonomous robotic system [38].

Evolving Technology and Future Perspectives
Newer designs of miniaturized HUD and wireless transducers are being evaluated, including wearable, belt-like and vascular imaging [45]. Tissue Doppler Imaging (TDI), three-dimensional (3D) and advanced technologies are mostly lacking or limited in currently available devices. With the further development of the novel ultrasound-on-chip technology, more applications would be readily available for real-time use. Additionally, the increasing repertoire of available artificial intelligence applications is expected to advance even more in coming years, including automatic indices measurements, quality grading and acquisition real-time improvement feedback [46,47]. These tools can be used as decision support tools for diagnostic accuracy improvement, acquisition optimization, multiple image interpretation integration and reduction in variability. Many of these applications are mainly relevant for non-expert operators. Moreover, the combination of image digitalization and tele-robotics may expand the use of ultrasound even further, enabling experts to perform an examination from a distance, thus virtualizing both interpretation and ultrasound image acquisition via semi-autonomous robotic system [38].

Conclusions
HUD-based echocardiographic assessment is a useful and accurate adjunctive tool in the management of COVID-19 patients. The portability, low-cost and instantaneous nature of this easily infection-controlled imaging modality is invaluable for the pulmonary and cardiovascular real-time assessment in COVID-19 settings. HUD utilization also involves the shortening of operator-patient exposure time and can be incorporated early into routine patient management as a diagnosis support tool for risk stratification and clinical management tailoring. Offering department-specific designated devices and carrying no risk of radiation exposure, HUD can be utilized to augment the limited physical examination in heterogenous COVID-19 patient population, including pediatrics and pregnant patients. However, HUD is less suitable for advanced hemodynamic valvular assessment. As such, patients with valvular lesions are suspected to be beyond mild in severity and cases with equivocal findings should be referred for a formal echocardiogram using a high-end device. Additionally, the routine utilization of focused echocardiogram among COVID-19 low-risk patients is not recommended for prognostication or as a screening tool. Further research and new modalities are required to further establish the role of HUD in a COVID-19 setting.