key: cord-0740993-mvnpz6a0
authors: Barosi, Alberto; Bergamaschi, Luca; Cusmano, Ignazio; Gasperetti, Alessio; Schiavone, Marco; Gherbesi, Elisa
title: Echocardiography in COVID-19 pandemic: clinical findings and the importance of emerging technology
date: 2021-10-30
journal: Card Electrophysiol Clin
DOI: 10.1016/j.ccep.2021.10.007
sha: 26076aefa065da6566eb977d7201468e5b829c15
doc_id: 740993
cord_uid: mvnpz6a0

Coronavirus disease 2019 (COVID-19) could have a direct or indirect effect on the cardiovascular system. To detect cardiac involvement, trans-thoracic echocardiography (TTE), as a widely available and cost-effective tool, is highly recommended and can provide important information that can affect the clinical management of COVID-19 patients. Despite that, considering the risk of equipment contamination and personnel exposure, mainly focused echocardiographic evaluations instead of complete examination are recommended and the use of portable devices easy to disinfect with offline reporting is highly suggested. Accordingly, cardiac imaging examination should be considered only when it could change the clinical management or be lifesaving for the patients. COVID-19, through different mechanisms, could affect different sections of the heart and it is useful to analyze them separately during an echocardiographic examination. Regarding the left ventricle, the SARS-CoV-2 infection could lead to acute myocardial infarction, tako-tsubo syndrome and in particular acute myocarditis. The impairment of the pulmonary circulation and the higher prevalence of pulmonary embolism in these patients explain and correlate with some pathological findings as right ventricular systolic dysfunction and direct or indirect signs of pulmonary hypertension, which could easily be assessed by echocardiography and with notable prognostic meaning. Some reports also described acute pericarditis and cardiac effusion during SARS-COV-2 infection and echocardiography is the first recommended diagnostic tool to evaluate the pericardial involvement, especially to exclude signs of cardiac tamponade that rapidly deteriorate the clinical state of the patients. However, available echocardiographic data on COVID-19 patients are scarce and actually does not provide definite evidence and more studies are certainly needed to better evaluate this topic.

In COVID-19 have also been described cases of typical and atypical Takotsubo syndrome 22 , possibly triggered by emotional stress and physical stress by infection itself, with a significant increase in the incidence of stress cardiomyopathy when compared with prepandemic periods 23 : echocardiography have a diagnostic role in detecting the typical apical ballooning and possible unfavorable findings (left ventricular outflow tract obstruction, mitral regurgitation, apical thrombus) 24 .

Of particular interest, is COVID-19 related myocarditis: a direct cardiotropic localization of SARS-CoV-2 into myocytes has never been described, but some autoptic findings (lymphocyte infiltrates and macrophagic response) resulted compatible with viral myocarditis 25 . In a systematic review of Sawalha et al. comprising 14 cases with myocarditis/myopericarditis believed to have occurred secondary to COVID-19 infection, echocardiography was performed in most cases (83%) and 60% had reduced LVEF, with diffuse hypokinesis in 30% of patients 26 .

However, excluding specific clinical scenario, while big alterations at conventional echocardiography could be difficult to detect 27 , deformation imaging can be the appropriate tool to identify subclinical modifications 28 : in a study of Stobe et al., despite normal left ventricular ejection fraction (LVEF), most of infected patients (that ranged from mild to severe symptoms) showed abnormal LV deformation, in particular a reduced longitudinal strain observed predominantly in more than one basal LV segment (in 10/14 patients, 71%), that was attributed to a possible sub-epimyocardial involvement of SARS-CoV-2-induced myocarditis, confirmed by cardiac magnetic resonance (CMR) but only in 2 patients 29 . Left ventricular-global longitudinal strain (LV-GLS) was altered in up to 80% of patients hospitalized for COVID-19 infection 30 (32/40 patients, mean LV-GLS of 12.1%±4.0, normal <16%) and was superior to LVEF for predicting adverse outcome 31 . Indeed, an important role of echocardiography could be the prognostic stratification of patients: LV-GLS was found to be independent predictor of mortality through multivariate analysis 32,33,34 . J o u r n a l P r e -p r o o f A major role in COVID-19 is played by the right ventricle (RV): it could be affected secondarily to elevation in RV afterload; increases in PVR causes right ventricular dilation and eventual RV failure, which has been related to a worse prognosis 35 .

COVID-19 could cause ARDS through vasoactive mediators, vascular thrombosis, and vascular compression secondary to atelectasis and oedema 36 .

Moreover patients with COVID-19 are in a prothrombotic state that predisposes them to thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE) 37, 38, 39 .

The study by Dweck et al., a survey of the European Association of Cardiovascular Imaging, found that 33% of patients had an abnormal RV on echocardiography 40 . Of these subjects, 19% had mildto-moderate RV dysfunction and 6% had severe dysfunction (of note, the index used for the definition of dysfunction was not specified). The RV was dilated in 15%, a D-shaped LV was seen in 4% and pulmonary artery pressure was elevated in 8%.

In the study by Mahmoud-Elsayed et al. 41% of patients had a dilated RV (RV basal diameter >41 mm) and 27% has a decreased RV function (fractional area change <35% or a tricuspid annular plane systolic excursion < 17 mm); most patients had severe respiratory failure and 82% were on invasive mechanical ventilation. A PE was detected in 20% of subjects with RV dysfunction as compared with 2% in those without RV dysfunction 41 .

Jain et al. found that 15.3% of the patients had an increased RV size (12.5% were mildly increased and 2.8% were moderately increased) 42 . Right ventricular systolic function (assessed semiquantitatively) was mildly decreased in 26.4%, moderately decreased in 9.7% and severely decreased in 4.2%.

Several studies reported an association between right-side TTE parameters and prognosis in patients with COVID-19.

Kim et al. in an analysis from a US multicentre retrospective study reported that adverse RV remodelling (dysfunction/dilation) conferred a >2 fold increase in mortality risk 43 . J o u r n a l P r e -p r o o f Szekely et al. 44 found that the most frequent abnormality among patients with clinical deterioration during follow-up was RV dilatation (with or without dysfunction). In univariable analysis, they reported that shorter pulmonary acceleration time (<100 msec) was associated with clinical deterioration and that RV end-diastolic area was associated with mortality 44 .

Li et al. reported that RV global longitudinal strain was a powerful predictor of death in patients with COVID-19 45 .

In a recent systematic review, Messina et al. analyzed studies available in literaturet and concluded that they have highly variable sample sizes and reported highly heterogeneous findings: LVEF does not seem significantly affected (reported as higher than 50% in most subjects), LV diastolic function has not been properly assessed and RV dysfunction seems frequent but defined with variable criteria, making it difficult to establish a clear association with higher mortality 46 .

The presence of valvular heart disease (VHD) has been described in COVID-19 patients undergoing echocardiography during the hospital stay 40 . These valvular diseases more likely were present before the onset of SARS-CoV2 infection. A recent study regarding echocardiographic findings among COVID patients reported that half of them presented a significant tricuspid regurgitation followed by aortic regurgitation and mitral regurgitation 47 . Tricuspid regurgitation is the most common VHD reported in COVID-19 patients and its severity could directly reflect the impairment of the pulmonary circulation during the infection resulting in pulmonary hypertension, especially in patients with severe pneumonia and respiratory insufficiency 48 .

A higher concern, especially in COVID-19 patients in the intensive care unit, is the presence of infectious endocarditis (IE). Some clinical reports have reported endocarditis in a minority prevalence and the presence of valve vegetations were also described in autopsy findings for SARS-CoV2 patients 40, 49 . In this setting, endocarditis is related to bacterial endocarditis or the presence of Table 2 ) 50,60 . Adopting protocols aimed at reducing the amount of inappropriate studies, the workflow in echocardiography laboratories has declined in 50% and the study appropriateness has significantly increased 61 . Moreover, the use of limited tablet-based echocardiograms can reduce the study time by 79% 62 . Considering the importance of prone position in patients developing ARDS, some reports have suggested that prone position echocardiography might be feasible, allowing RV and LV evaluation in a four-chamber view 63 .

The need for absolute isolation of symptomatic patients and the high possibility of spreading the infection outside the isolation rooms in the High Intensity Care Departments, makes any attempt at an instrumental diagnostic approach difficult, given also the absolute need to decontaminate the equipment used after each individual examination. The advantages deriving from the execution of echocardiography examination at the patient's bedside are well known but the high risk of serious coronavirus infection diffusion has made its use difficult. Disinfection is the only way to counter the risk of spreading the disease from one patient to another or among the operators themselves, which event is even more dangerous because it would jeopardize the tightness of the system. Hand-carried (HC) echocardiography devices offer rapid and readily available information at the bedside, as they help overcome the problems caused by the use of cumbersome standard equipment 62, 64 . The use of "ultramobile devices" has recently been introduced in the area of cardiovascular ultrasound Moreover, in China, a pilot study of robot-assisted teleultrasound based on 5G Network was conducted 65 : ultrasound specialists carried out the robot-assisted teleultrasound, manipulating a handheld controller, which can control the robotic arm, and did remote consultation in order to settle the problem of early cardiopulmonary evaluation in COVID-19 patients.

A point of particular importance is the role of artificial intelligence (AI), technology that creates a computerized model to solve different problems without the requirement of human assistance, J o u r n a l P r e -p r o o f continuously learns from the dataset and predicts outcomes accurately 66, 67 . It was used in intensive care unit by critical care physicians without formal training in ultrasound to obtain POCUS images, with the use of real-time prescriptive guidance to direct the physician's transducer position and hand movements to acquire the images, automatically capturing them when appropriate, detecting LVEF with high accuracy, and uploading to the archive and communication system for offline review 68 . AI includes machine learning (ML), which offers the potential to improve the accuracy and reliability of echocardiography by combining clinician interpretation with information derived from ML algorithms. In conclusion, high volume data generated from cardiac imaging can be integrated in a multiparametric approach for pattern recognition and imaging data-based disease phenotype characterization, particularly useful and time-saving in the setting on COVID-19 pandemic 69 .

Echocardiography has a diagnostic and prognostic role in COVID-19, helping in recognizing cardiac involvement. Considering the high risk of personnel infection and equipment contamination, focussed echocardiographic protocols with portable device are recommended.

Available echocardiographic data on COVID-19 patients actually do not provide definite evidence, due to multiple factors: high heterogeneity between studies in numbers of patients, miscellaneous results and low quality of echocardiographic studies for technical difficulties in performing bedside procedures (patients with respiratory distress/invasive ventilation; while wearing personal protective equipment).

In conclusion, echocardiography represents an important tool in the management of COVID-19

patients, but more studies with standardized acquisitions and methods are needed to describe definite echocardiographic findings in this setting. 

-Perform urgent/emergent exams (that can change patient management or be lifesaving, in particular for TOE) -Defer elective/routine follow-up exams 

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