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JACC: CARDIOVASCULAR IMAGING

VOL. 13, NO. 8, 2020

ª 2020 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

STATE-OF-THE-ART REVIEW

Heart and Lung Multimodality Imaging in COVID-19 Eustachio Agricola, MD,a,b Alessandro Beneduce, MD,b,c Antonio Esposito, MD,b,d Giacomo Ingallina, MD,a,b Diego Palumbo, MD,b,d Anna Palmisano, MD,b,d Francesco Ancona, MD,a,b Luca Baldetti, MD,b,e Matteo Pagnesi, MD,b,e Giulio Melisurgo, MD,b,f Alberto Zangrillo, MD,b,g Francesco De Cobelli, MDb,d

ABSTRACT The severe acute respiratory syndrome-coronavirus-2 outbreak has rapidly reached pandemic proportions and has become a major threat to global health. Although the predominant clinical feature of coronavirus disease-2019 (COVID-19) is an acute respiratory syndrome of varying severity, ranging from mild symptomatic interstitial pneumonia to acute respiratory distress syndrome, the cardiovascular system can be involved in several ways. As many as 40% of patients hospitalized with COVID-19 have histories of cardiovascular disease, and current estimates report a proportion of myocardial injury in patients with COVID-19 of up to 12%. Multiple pathways have been suggested to explain this finding and the related clinical scenarios, encompassing local and systemic inflammatory responses and oxygen supply-demand imbalance. From a clinical point of view, cardiac involvement during COVID-19 may present a wide spectrum of severity, ranging from subclinical myocardial injury to well-defined clinical entities (myocarditis, myocardial infarction, pulmonary embolism, and heart failure), whose incidence and prognostic implications are currently largely unknown because of a significant lack of imaging data. Integrated heart and lung multimodality imaging plays a central role in different clinical settings and is essential in the diagnosis, risk stratification, and management of patients with COVID-19. The aims of this review are to summarize imaging-oriented pathophysiological mechanisms of lung and cardiac involvement in COVID-19 and to provide a guide for integrated imaging assessment in these patients. (J Am Coll Cardiol Img 2020;13:1792–808) © 2020 by the American College of Cardiology Foundation.

T

he

syndrome-

challenged with different and complex clinical sce-

coronavirus-2 (SARS-CoV-2) outbreak arisen

severe

narios. The most prominent feature of COVID-19 is

in central China at the end of December

an acute respiratory syndrome of varying severity,

2019 has rapidly reached pandemic proportions and

ranging from mild symptomatic interstitial pneu-

the associated coronavirus disease-2019 (COVID-19)

monia

has become a major threat to global health (1). As

(ARDS). However, several reports have directed

the

attention

pandemic

acute

grows,

respiratory

treating

physicians

are

to

acute

respiratory

toward

distress

possible

syndrome

cardiovascular

From the aCardiovascular Imaging Unit, Cardio-Thoracic-Vascular Department, IRCCS San Raffaele Scientific Institute, Milan, Italy; bSchool of Medicine, Vita-Salute San Raffaele University, Milan, Italy; cInterventional Cardiology Unit, Cardio-ThoracicVascular Department, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department, IRCCS San Raffaele Scientific Institute, Milan, Italy;

e

d

Experimental Imaging Center, Radiology

Cardiac Intensive Care Unit, Cardio-Thoracic-Vascular

Department, IRCCS San Raffaele Scientific Institute, Milan, Italy; fCardiothoracic Intensive Care Unit, Cardio-Thoracic-Vascular Department, IRCCS San Raffaele Scientific Institute, Milan, Italy; and the gAnesthesia and Intensive Care Unit, Anesthesia and Intensive Care Department, IRCCS San Raffaele Scientific Institute, Milan, Italy. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Cardiovascular Imaging author instructions page. Manuscript received April 9, 2020; revised manuscript received May 27, 2020, accepted May 28, 2020.

ISSN 1936-878X/$36.00

https://doi.org/10.1016/j.jcmg.2020.05.017

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

1793

Multimodality Imaging in COVID-19

involvement during SARS-CoV-2 infection: as many

the disease and leading to unfavorable out-

ABBREVIATIONS

as 40% patients hospitalized with COVID-19 have his-

comes (Central Illustration).

AND ACRONYMS

CARDIOVASCULAR INVOLVEMENT

syndrome(s)

tory of cardiovascular disease, and current estimates report a proportion of myocardial injury in patients with COVID-19 of up to 12% (2–4). Identification of myocardial injury is associated with a dismal prognosis independently and in addition to coexisting cardiovascular diseases, so recognition of underlying mechanisms may offer a therapeutic opportunity (4). In this context, the use of multiple diagnostic imaging techniques may apply to both the heart and lungs to provide an integrated assessment of cardiac and pulmonary function and to refine diagnosis, risk stratification, and management among patients with COVID-19.

ACS = acute coronary

IN COVID-19

ARDS = acute respiratory distress syndrome

Definition of cardiac involvement in COVID19 is challenging, as SARS-CoV-2 infection has multifaceted effects. From a clinical point of view, cardiac involvement during COVID19 may present a wide spectrum of severity, ranging from subclinical myocardial injury to well-defined clinical entities. In a comprehensive understanding, the following clinical scenarios may be encountered: 1) primary cardiac involvement; 2) secondary cardiac

PATHOGENESIS AND

CMR = cardiac magnetic resonance

COVID-19 = coronavirus disease-2019

CT = computed tomography CXR = chest radiography ED = emergency department FoCUS = focused cardiac ultrasound

GGO = ground-glass opacity ICA = invasive coronary

CLINICAL MANIFESTATIONS OF COVID-19

involvement; and 3) worsening of previous

The pathogenesis of COVID-19 is characterized by 2

PRIMARY

distinctive but synergistic mechanisms, the first

may be a consequence of viral tropism for the

related to viral replication and the second to the host

endothelium

immune response (5). The disease primarily involves

myocardium. A link between the respiratory

infarction with nonobstructive

the lungs and progresses through 3 stages of

syndrome and the pleomorphic cardiovascu-

coronary arteries

increasing severity, corresponding to distinct histo-

lar manifestations associated with COVID-19

PE = pulmonary embolism

pathologic, imaging, and clinical findings (6–8).

cardiovascular diseases (Table 1). CARDIAC

and

ICU = intensive care unit

INVOLVEMENT. This

(presumably)

angiography

for

the

LUS = lung ultrasound MI = myocardial infarction MINOCA = myocardial

could be identified in angiotensin convert-

PPE = personal protection

The first stage involves the incubation period,

ing enzyme 2, a membrane-bound enzyme

equipment

SARS-CoV-2 replication in the respiratory system, and

that serves as cell-entry receptor for SARS-

RT-PCR = reversetranscriptase polymerase chain

potential spread to target organs. During this phase,

CoV-2 (9). This receptor is expressed in a va-

alveolar and interstitial inflammation is mild and

riety of tissues, including lung alveolar

patchy and usually shows a bilateral, peripheral, and

epithelial cells and enterocytes of the small

respiratory syndrome-

lower distribution, with patients presenting with mild

intestine, as well as arterial smooth muscle

coronavirus-2

respiratory and systemic symptoms.

reaction

SARS-CoV-2 = severe acute

cells and endothelial cells (9). On the basis of

TEE = transesophageal

The second stage is characterized by localized lung

previous data from the SARS-CoV epidemic,

echocardiography

inflammation, which shows different grades of

myocardial infection by coronavirus is a

TTE = transthoracic echocardiography

severity, ranging from severe interstitial inflamma-

possibility: in an autopsy series, SARS-CoV

tion and thickening to air-space consolidation. Pa-

ribonucleic acid was found in 35% of sampled

tients develop symptoms of viral pneumonia and

hearts,

eventually hypoxia, leading to clinical deterioration

myocardial damage (10). The extent to which these

along

with

macrophage

infiltration

and

and need for hospitalization.

finding may also apply to SARS-CoV-2 is unknown. To

In a subgroup of patients, transition to the third

date, no cases of SARS-CoV-2 nucleic acid isolation

stage occurs. This phase is dominated by widespread

from myocardial specimens have been described.

lung inflammation and systemic inflammatory syn-

However, several cases have reported on the occur-

drome triggered by a dysregulated host immune

rence of severe myocarditis during laboratory-proven

response

hyper-

COVID-19 (11–15). In all these cases, myocarditis

inflammation, ARDS, shock, and multiorgan damage.

caused severe left ventricular dysfunction but showed

Clinical

and

cytokine

features

of

storm, COVID-19

causing

variable.

some degree of systolic function recovery following

Although the majority of patients present with only

are

medical therapy, ranging from progressive improve-

mild respiratory and systemic symptoms, some

ment to complete myocardial function restoration. A

progress to severe forms of viral pneumonia and

single case of myopericarditis complicated by life-

eventually develop severe systemic inflammatory

threatening cardiac tamponade has been reported,

manifestations, with an increasingly higher case fa-

again without direct isolation of SARS-CoV-2 from the

tality rate (7). Cardiovascular adverse events may

drained pericardial fluid (12). In the absence of proven

occur at different stages, complicating the course of

SARS-CoV-2 infection of the myocardium, the clinical

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

Multimodality Imaging in COVID-19

C E N T R A L IL LU ST R A T I O N Pathogenesis, Imaging, and Clinical Progression of Coronavirus Disease 2019

Viral replication

Immune response Pathology

Lung involvement LUS / CXR / CT

RV involvement TTE

Stage I Early infection

Stage II Pulmonary phase

Stage III Systemic inflammation

Cardiac complications Risk of Adverse Outcome

1794

Time Agricola, E. et al. J Am Coll Cardiol Img. 2020;13(8):1792–808.

Viral replication and host immune response synergistically determine coronavirus disease 2019 pathogenesis. As the disease progresses through its 3 stages, different chest imaging modalities (lung ultrasound, chest radiography, and computed tomography) demonstrate worsening lung involvement. In case of severe pneumonia, transthoracic echocardiography can identify increasing pulmonary hypertension and right ventricular impairment. Cardiovascular complications related to viral infection or to systemic inflammation can occur at different stages of the disease, increasing the risk for adverse outcome, and require specific multimodality imaging assessment. CT ¼ computed tomography; CXR ¼ chest radiography; LUS ¼ lung ultrasound; RV ¼ right ventricular; TTE ¼ transthoracic echocardiography.

overlap of these case reports with other possible dif-

by interleukin-1 and interleukin-6 pathways, closely

ferential diagnoses calls for prudence in diagnosing

resembling hemophagocytic lymphohistiocytosis, a

SARS-CoV-2-related myocarditis.

life-threatening hematologic disorder characterized by uncontrolled proliferation of activated lympho-

SECONDARY CARDIAC INVOLVEMENT. This is the

cytes and macrophages, with massive release of in-

result of indirect myocardial damage during SARS-

flammatory cytokines (9). These cytokines have been

CoV-2 infection. Of note, it may represent the

implicated in myocardial injury and adverse remod-

convergence

mechanisms.

eling in clinical and experimental models of acute

In a post-mortem examination from a patient with

coronary syndrome(s) (ACS) and may exhibit direct

COVID-19 who developed ARDS, interstitial mono-

negative inotropic and metabolic effects on car-

nuclear inflammatory cells were noted in heart spec-

diomyocytes in sepsis-like settings (17). In addition,

imens

A

interleukin-1 plays a proven role in atherothrombosis,

hyperinflammatory response in the advanced stage of

and the resulting hyperinflammatory milieu may

the disease elicits a cytokine storm, mediated chiefly

provoke atherosclerotic plaque instability and a

of

without

multiple

different

structural

damage

(16).

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

procoagulant state with increased risk for arterial and venous acute thrombotic events, including type 1 myocardial infarction (MI) and pulmonary embolism (PE).

Indeed,

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Multimodality Imaging in COVID-19

there

is

increasing

concern

that

patients with COVID-19 are more prone to develop

T A B L E 1 Cardiovascular Involvement in Coronavirus Disease 2019

Pathogenetic Mechanism

Clinical Manifestations

Imaging Modalities

Primary cardiac involvement Viral myocarditis

TTE CMR

Cytokine storm

Inflammatory myocarditis

TTE CMR

Oxygen supply-demand imbalance

Type 2 MI

TTE CT/ICA CMR

(CAD) or present as MI with nonobstructive coronary

Inflammatory prothrombotic state Atherosclerotic plaque instability

Type 1 MI

TTE CT/ICA

arteries (MINOCA) in the presence of intense oxygen

Inflammatory prothrombotic state

VTE and acute PE

TTE CT

Lung inflammation Hypoxic vasoconstriction High-PEEP mechanical ventilation Pulmonary thromboembolism

RV increased afterload

TTE

Infection-related metabolic demand Cytokine storm

Heart failure exacerbation

TTE

Hypoxia Cytokine storm Drug side effects (QT interval prolongation: hydroxychloroquine and azithromycin alone or in combination with AADs)

Arrhythmias

thromboembolic venous events and disseminated intravascular coagulation (18,19). Secondary cardiac involvement

may

also

be

the

consequence

of

hypoxia-induced myocardial damage, which could

Direct viral damage (hypothesized) Secondary cardiac involvement

lead to type 2 MI. This condition could either unmask underlaying

obstructive

coronary

artery

disease

supply-demand imbalance (20). Moreover, altered pulmonary hemodynamic status may play a role in secondary cardiac involvement. In severe COVID19 pneumonia, the use of higher positive endexpiratory

pressure

may

be

associated

with

increased right ventricular afterload and strain due to higher pulmonary arterial pressure and pulmonary vascular resistance. Pulmonary circulation hypoxic vasoconstriction

and

superimposed

pulmonary

thromboembolic events may further precipitate these effects. WORSENING OF PRE-EXISTING CARDIOVASCULAR DISEASES. This

is

frequently

observed

of patients with pre-existing cardiovascular comorbidities in nonsurvivor cohorts (3,4,21). Indeed, patients with heart failure are particularly vulnerable to decompensation

during

viral

in-

fections (22). Furthermore, in predisposed patients, arrhythmias may ensue as a result of multiple mechanisms, including hypoxia, systemic inflammation, and side effects of drugs used in the treatment of COVID-19 (i.e., hydroxychloroquine often combined with azithromycin) (2).

MULTIMODALITY IMAGING IN COVID-19

—

AAD ¼ antiarrhythmic drug; CMR ¼ cardiac magnetic resonance; CT ¼ computed tomography; ICA ¼ invasive coronary angiography; MI ¼ myocardial infarction; PE ¼ pulmonary embolism; PEEP ¼ positive end-expiratory pressure; RV ¼ right ventricular; TTE ¼ transthoracic echocardiography; VTE ¼ venous thromboembolism.

during

COVID-19 and may explain the higher prevalence

hemodynamic

Worsening pre-existing conditions

that portable CXR might be considered the optimal tool to minimize the risk for cross-infection (23). As recently reported, CXR demonstrates typical radiographic features in the vast majority of patients with COVID-19, including ground-glass opacities (GGOs) and consolidation, while pleural effusion is not common (Table 2, Figure 1). In a retrospective cohort of 64 patients, Wong et al. (24) found that the common computed tomographic findings of bilateral involvement, peripheral distribution, and lower zone dominance can also be assessed on CXR and that the severity of findings on CXR peaked at 10 to 12 days after symptom onset, consistent with previous re-

CHEST RADIOGRAPHY. Recent radiology research on

ports with CT (24). Although 6 of 64 patients

COVID-19 has been molded by the Chinese experi-

demonstrated abnormalities on CXR before eventu-

ence, with the vast majority of reports focusing on the

ally testing positive on RT-PCR, baseline CXR sensi-

role of chest computed tomography (CT), almost

tivity was 69%, significantly lower than that reported

neglecting the contribution of chest radiography

for initial RT-PCR and baseline CT (25). Moreover, in

(CXR). However, European hospitals have drawn

contrast to what has been previously reported for

diagnostic algorithms in which CXR is described as a

chest CT, radiographic and virological recovery times

first-line triage tool, mainly because of its availability

were not significantly different, thus reducing the

and feasibility and long turnaround times for reverse-

role of CXR in clinical monitoring (25). A retrospective

transcriptase polymerase chain reaction (RT-PCR)

analysis of 9 South Korean patients who underwent

analysis. Furthermore, the American College of

both chest CT and CXR further decreased the sensi-

Radiology has pointed out that CT room decontami-

tivity of CXR in detecting COVID-19 pneumonia to

nation after scanning patients with COVID-19 may

33.3% (26). However, the significance of this result is

disrupt radiological service availability and suggested

limited by the small sample size. Recently, Bandirali

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Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

Multimodality Imaging in COVID-19

T A B L E 2 Integrated Multimodality Imaging Findings in COVID-2019 Pneumonia

CXR

—

CT

LUS

Thickened pleura

Thickened pleural line

Blurred opacities*

Ground-glass opacities

Multiple B-lines (cometlike)

Patchy or diffuse opacities

Crazy paving pattern

Confluent B-lines (white lung)

Localized consolidation

Subpleural consolidation

Subpleural consolidation

Translobar consolidation

Translobar consolidation

Extensive consolidation with hypoechoic lung tissue (hepatization) and air bronchograms

Bilateral distribution of lung changes with predominance in lower and peripheral zones Pleural effusion is rare *The term “ground-glass opacities” is also used in CXR to refer to areas of blurred opacities. CT ¼ computed tomography; CXR ¼ chest radiography; LUS ¼ lung ultrasound.

et al. (27) proposed a role for CXR in asymptomatic or

had initial positive results on chest CT consistent

minimally symptomatic patients in epidemic regions,

with COVID-19, before the initial positive RT-PCR

who may have positive radiographic findings even

results

after 14 days of quarantine. To date, there are no

improvement on follow-up chest CT before RT-PCR

consistent findings accurately depicting the course of

results became negative (25). Nevertheless, it is

disease on serial CXR.

worth emphasizing that patients with RT-PCR-

(25).

Finally,

42%

of

patients

showed

CHEST CT. Chest CT is a highly accurate imaging

confirmed COVID-19 might have normal findings on

modality for pneumonia identification and charac-

chest CT at admission, when disease is still subtle

terization. As recently reported, chest CT demon-

(30). Additionally, chest CT can be used for charac-

strates typical imaging features in patients with

terization of COVID-19 pneumonia severity. Yang

COVID-19, including bilateral GGOs, crazy paving

et al. (31) proposed a CT-based severity score defined

pattern (GGOs with superimposed interlobular or

by summing individual scores from 20 lung regions;

intralobular septal thickening), and/or consolida-

the individual scores in each lung, as well as the

tions, predominantly in subpleural locations in the

global severity score, were found to be higher in pa-

lower lobes; typically, discrete pulmonary nodules,

tients with severe COVID-19 compared with those

lung cavitation, pleural effusion, and lymphadenop-

with mild disease (sensitivity 83.3%, specificity 94%).

athies are not present (28,29) (Table 2, Figure 2). Pan et al. (28) demonstrated that multiple computed

LUNG ULTRASOUND. Lung ultrasound (LUS) is a

tomographic scans could accurately depict the course

widespread and validated technique for lung evalu-

of disease, summarized in 4 CT-based stages. Typical

ation with features that make it very attractive for the

COVID-19 pneumonia often starts as small subpleural

assessment of patients affected by COVID-19 (32–34).

GGOs, mainly affecting the lower lobes (early stage,

LUS can be performed with any 2-dimensional scan-

0 to 4 days after symptom onset), which then rapidly

ner, including portable ones, using linear, convex, or

develop into crazy paving pattern and consolidation

phased-array probes. Specifically, a high-frequency

areas, typically affecting both lungs (progressive

linear probe is recommended to assess the pleural

stage, 5 to 8 days after symptom onset). Thereafter,

line, a phased-array low-frequency probe is suggested

dense consolidation becomes the most frequent

to evaluate deep consolidation, and a micro convex

finding (peak stage, 9 to 13 days after symptom

probe with a small footprint is useful for evaluating

onset). When infection resolves, the consolidation

posterior fields in supine patients. The entire chest

areas are gradually absorbed with residual GGOs and

can be scanned with the probe oriented longitudi-

subpleural fibrotic parenchymal bands (absorption

nally or obliquely along the intercostal spaces. The

stage, >2 weeks after symptom onset) (Figure 2). Ai

scanning protocol consists of a 12-zone examination

et al. (25) found that with RT-PCR as a reference, the

with 6 regions per hemithorax: the upper and lower

sensitivity of chest CT for COVID-19 was 97%. Inter-

parts of the anterior, lateral, and posterior chest wall,

estingly, these radiological findings are also observed

demarcated by the anterior and posterior axillary line

in patients with clinical symptoms but negative RT-

(32,33).

PCR results, and almost 50% and 33% of these pa-

COVID-19 pneumonia is characterized by initial

tients were reconsidered as highly likely cases and as

interstitial damage with a bilateral, peripheral, and

probable cases, respectively, in a comprehensive

posterior

evaluation (25). Furthermore, 60% to 93% of patients

involvement (34). LUS effectively detects the areas

distribution

followed

by

parenchymal

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

Multimodality Imaging in COVID-19

F I G U R E 1 Chest Radiographic Features of COVID-19 Pneumonia

(A) A 67-year-old-man presenting with sore throat: blurred peripheral ground-glass opacities (GGOs), mainly in the left medium to lower lung, with diffuse, blurred interstitial thickening. (B) A 59-year-old-man presenting with fever (39.5 C), cough, and diarrhea: diffuse, bilateral peripheral GGOs, consolidation areas mainly in the left lower lung and in the medium right lung. (C) A 43-year-old woman presenting with fever (40.5 C), cough, dyspnea, and severe hypoxia: bilateral consolidation areas occupying almost all lung parenchyma, with gross GGOs. No pleural effusion was noted in any case.

affected by subpleural interstitial syndrome with the

TRANSTHORACIC AND TRANSESOPHAGEAL ECHO-

appearance of B-lines, which increase in number as

CARDIOGRAPHY. Although echocardiography should

the pathology spreads, covering most of the pleural

not routinely be performed in patients with COVID-19

line. These findings correspond to GGOs and a retic-

and restricted to those in whom it is likely to result in

ular pattern on CT (Table 2). The characteristics of the

a change in management, bedside echocardiography

B-lines help distinguish within interstitial syndrome

is a clinically useful tool in different clinical settings

between pneumonia or ARDS and cardiogenic pul-

in emergency departments (EDs), intensive care units

monary edema. Specifically, inflammatory patterns

(ICUs), and non-ICU wards (35). Compact and highly

are characterized by the presence of bilateral, irreg-

mobile machines should be the ideal ultrasound sys-

ularly distributed B-lines with spared areas and coa-

tems to adopt, privileging dedicated probes and ma-

fields;

chines in infected areas. A miniaturized handheld

furthermore, the pleural line appears typically thick-

ultrasound system that can be easily protected and

ened and irregular, with reduced or absent lung

cleaned may be an alternative option (35,36).

lescent

B-lines

mostly

in

posterior

sliding (32). As the disease progresses, lung consoli-

A pragmatic strategy based on the use of focused

dations become frequent. The subpleural consolida-

cardiac ultrasound (FoCUS) seems the most reason-

tion areas are identified as anechoic hemispheric

able approach (37). FoCUS should be combined with

areas close to the pleural line with a hyperechogenic

LUS for the evaluation of patients with respiratory

base.

non-

failure. The COVID-19 crisis highlights the need for

translobar and translobar consolidation with hepati-

imagers to be cross-trained (LUS and FoCUS) and

zation of lung tissue and air bronchogram, which

nimbler: sonographers, cardiologists, and emergency

distinguish them from consolidations in resorptive

physicians who are not familiar with LUS can learn

atelectasis (Figure 3). However, LUS also presents

quickly with initial support from expert colleagues

limitations, as it is operator dependent, and abnor-

and web resources (38). However, because FoCUS is

malities affecting the central regions surrounded by

not performed as the definitive diagnostic test, if no

aerated lung are not detectable. With the aim of

usable

increasing reproducibility, it would be convenient to

echocardiography and/or other diagnostic testing

establish a scanning model and a severity score. The

must be considered (37). The aim of echocardiography

LUS score, validated with chest CT comparison, pro-

is to reliably identify cardiac abnormalities and

vides a numeric assessment of regional loss of aera-

coexisting heart disease to facilitate triage and guide

tion that can be used to assess the response to

patient management. Echocardiography is also rec-

treatments (33) (Figure 3).

ommended for the evaluation of patients who

Extensive

consolidation

appears

as

information

is

obtained,

comprehensive

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1798

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

Multimodality Imaging in COVID-19

F I G U R E 2 Computed Tomographic Features and Staging of COVID-19 Pneumonia

The early stage (A) of typical COVID-2019 pneumonia is characterized by small subpleural ground-glass opacities (box), which then rapidly increase in number and develop into crazy paving pattern during the progressive stage (B). In the peak stage (C), dense consolidation becomes the most frequent finding. During the absorption stage (D), when the disease has a favorable course, consolidation areas are gradually absorbed, with residual subpleural fibrotic parenchymal bands (arrows).

develop symptoms consistent with a cardiac etiology.

combination of dyspnea and chest pain, electrocar-

Information

diographic alterations, and cardiac enzyme disper-

must

quickly

include

biventricular

function, gross valvular abnormalities, wall motion

sion,

abnormalities, pericardial effusions, and surrogates

pulmonary and cardiovascular etiology of these

challenging

of a patient’s volume status, including inferior vena

findings and requiring advanced imaging to clarify

cava collapsibility and ventricular size (37). Trans-

the diagnosis. Several reports hint at an increased

thoracic echocardiography (TTE) is the standard

risk for venous and arterial thromboembolism,

technique, while transesophageal echocardiography

while our clinical experience and other reports

(TEE) should be avoided because of the high risk for

suggest that some patients with COVID-19 present-

equipment and personnel contamination, unless

ing

there is a clearly defined indication that requires TE

obstructive CAD on invasive coronary angiography

or inadequate imaging quality on TTE because of

(ICA), falling into the wide spectrum of MINOCA

with

ACS-like

the

differentiation

syndromes

may

between

not

have

patient-specific factors (intubated patients, poor im-

(19,20). In this clinical scenario, CT may represent a

age quality, inability to position critically ill patients

valuable “one-stop shop” approach for the com-

for optimal image acquisition) (35). The most com-

bined assessment of pneumonia, PE (Figure 4), and

mon echocardiographic abnormalities encountered in

obstructive CAD (Figure 5) to guide further man-

our experience on patients with COVID-19 in the non-

agement, limiting the use of ICA to selected cases

ICU setting are reported in Table 3. Acute worsening of respiratory symptoms is a leading indication for

(Figure 6). Computed tomographic coronary angiography is a

performing

patients,

well-established tool to effectively and safely rule out

frequently depicting a picture of acute cor pulmonale:

CAD in the setting of acute chest pain, thanks to its

right ventricular dilatation, paradoxical septal mo-

excellent negative predictive value (95% to 100%)

tion, and pulmonary hypertension. In this clinical

(39). Of note, computed tomographic angiography

setting PE seems relatively frequent (Figure 4).

can combine coronary artery, pulmonary artery,

Echocardiography may expedite diagnosis of this

and thoracic aorta assessment using dedicated “tri-

condition.

ple-rule-out” protocols. In selected patients with

CARDIAC

echocardiography

CT

AND

MAGNETIC

in

these

RESONANCE. The

variable degrees of respiratory symptoms, showing

clinical presentation of patients with suspected or

cardiac enzyme and D -dimer elevations, a dedicated

confirmed COVID-19 may encompass a variable

triple-rule-out

approach, with lung parenchyma

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

Multimodality Imaging in COVID-19

F I G U R E 3 Lung Ultrasound Features and Severity Grading of COVID-19 Pneumonia

Different patterns of lung involvement and corresponding lung ultrasound (LUS) severity score. (A) Normal lung: horizontal A-lines (arrows) arising from the pleural line (arrowhead) at regular intervals. (B) Moderate loss of aeration: multiple cometlike B-lines (arrows) arising from focally thickened pleural line (arrowheads). (C) Severe loss of aeration: multiple coalescent B-lines responsible for a white lung appearance (square sign) along with pleural line thickening (arrowheads); subpleural consolidation (asterisk) visible as a focal hypoechoic area. (D) Complete loss of aeration: pleural line thickening (arrowhead) and extensive lung consolidation visible as a large hypoechoic area (asterisks) with associated air bronchogram (arrow).

instead of the thoracic aorta as the third focus of the

advised, as dedicated scanners can improve image

examination, may solve different clinical questions in

quality. Additionally, computed tomographic angi-

one sitting (40). Although most of the currently

ography can rule out left atrial appendage thrombus,

available computed tomographic scanners allow im-

allowing direct-current cardioversion in patients with

aging of the coronary arteries with high resolution

atrial fibrillation, thereby limiting operator exposure

and limited motion artifacts, clinical judgment is

deriving from TEE. Moreover, cardiac CT can provide advanced diagnostic assessment through myocardial characterization (41). Indeed, CT can be completed

T A B L E 3 Transthoracic Echocardiographic Findings in a

Single-Center, Nonintensive Care Unit COVID-19 Cohort From San Raffaele Hospital, Milan, Italy (N ¼ 209)

with a delayed iodine-enhanced scan to identify areas of myocardial necrosis or fibrosis. This further evaluation may be especially useful in patients with

Poor acoustic window

11/209 (5.3)

LVEF (%)

59 (55–63)

LVEF <50%

12/198 (6.0)

RWMAs

9/198 (4.5)

RV dilation*

23/198 (11.6)

and

myocardial scar with typical nonischemic pattern. In

MINOCA, making it possible to differentiate MI from stress cardiomyopathy, which is typically characterized by an absence of myocardial late enhancement, to

diagnose

acute

myocarditis,

detecting

RV dysfunction†

28/198 (14.1)

PH‡

24/198 (12.1)

this case, one can speak of “quadruple rule-out,” with

sPAP (mm Hg)

28 (23–33)

a single examination looking for lung involvement,

CVP 10–20 mm Hg

5/198 (5.0)

coronary

Values are n/N (%) or median (interquartile range). *RV dilatation has been defined as RV mid diameter >35 mm. †RV dysfunction has been defined as either tricuspid annular plane systolic excursion <17 mm or Doppler tissue imaging S wave (S0 wave) <9.5 cm/s. ‡PH has been defined as sPAP >35 mm Hg. CVP ¼ central venous pressure; LVEF ¼ left ventricular ejection fraction; PH ¼ pulmonary hypertension; RV ¼ right ventricular; RWMA ¼ regional wall motion abnormality; sPAP ¼ systolic pulmonary arterial pressure.

and

pulmonary

artery

patency,

and

myocardial scar (42). However, cardiac CT remains limited in the detection of myocardial edema, which represents the hallmark of acute myocardial inflammation (41). Cardiac magnetic resonance (CMR) is the imaging modality of choice for the diagnosis of acute

1799

1800

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F I G U R E 4 Multimodality Imaging of Pulmonary Embolism Complicating COVID-19 Pneumonia

A 61-year-old woman with reverse-transcriptase polymerase chain reaction swab results positive for severe acute respiratory syndrome coronavirus-2 presenting with sudden severe dyspnea associated with significant D-dimer increase. (A) Lung parenchyma windowing demonstrates bilateral, subpleural ground-glass opacities and consolidation areas (box), typical for coronavirus disease 2019 pneumonia. (B) Computed tomographic pulmonary angiography shows gross filling defect (arrows) in right pulmonary artery lobar branch for right upper lobe. (C, D) Transthoracic echocardiography shows right ventricular dilatation and septal shifting, indirect signs of severe pulmonary hypertension.

myocarditis, revealing with high sensitivity focal or

techniques in CMR protocols adopted in patients with

diffuse myocardial edema through short-tau inversion

COVID-19 with suspected myocarditis (43). Therefore,

recovery sequences and mapping techniques (T2 and

in selected patients with COVID-19 not requiring ICU

native T1), potentially associated with necrotic foci

support, when clinical presentation and biomarker

visible with late gadolinium enhancement, diffuse

alterations suggest acute-onset myocardial inflam-

expansion of extracellular volume fraction, and hy-

mation, if the diagnosis is likely to influence manage-

peremia (43,44) (Figure 5). The recent introduction of

ment, CMR may be considered to confirm acute

parametric mapping enables CMR to reveal diffuse

myocarditis, after the exclusion of alternative relevant

myocardial edema that can be missed by conventional

clinical conditions, including ACS and heart failure, by

sequences, increasing its accuracy in the diagnosis of

means of other rapidly available imaging modalities

inflammatory cardiomyopathies. Currently, a few case

(i.e., cardiac CT or TTE).

reports have shown CMR findings consistent with acute myocarditis in patients with laboratory-proven

NUCLEAR CARDIOLOGY IMAGING. Nuclear cardiol-

SARS-CoV-2 infection (13–15). Myocardial edema was

ogy encompasses several noninvasive imaging mo-

the key for CMR diagnosis in all of these cases,

dalities and techniques that can be used for myocardial

underscoring the importance of including mapping

perfusion and viability assessment, as well as for the

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F I G U R E 5 Multimodality Imaging of Myocardial Infarction With Nonobstructive Coronary Arteries Complicating COVID-19 Pneumonia

A 58-year-old woman with reverse-transcriptase polymerase chain reaction swab results positive for severe acute respiratory syndrome-coronavirus-2 presenting after 1 week of fever (38.5 C), cough, diarrhea with recent onset of typical chest pain, elevated cardiac markers (high-sensitivity troponin T 222 ng/l), ST-segment depression in the inferior and lateral leads on electrocardiography, and inferior septal hypokinesia on transthoracic echocardiography. Triple rule-out computed tomography shows peripheral lung opacities (A, B) characterized by crazy paving pattern involving both the inferior lobes, with posterior distribution, suggestive for coronavirus disease 2019 interstitial pneumonia (boxes), and demonstrates absence of pulmonary embolism (C) or coronary disease (D). Cardiac magnetic resonance shows slight diffuse myocardial hyperintensity on T2 short-tau inversion recovery image (E), consistent with a slight increase of T2 relaxation time on T2 mapping: mean value of 55 ms (normal range #50 ms) with a peak of 61 ms in the inferior septum (G); inversion recovery images do not show significant late gadolinium enhancement foci. LAD ¼ left anterior descending coronary artery; LCX ¼ left circumflex coronary artery; RCA ¼ right coronary artery.

diagnosis of infective endocarditis, cardiac sarcoid-

diagnosis and interventional treatment (46). In addi-

osis, and amyloidosis. However, most of these condi-

tion, ICA eventually combined with coronary intra-

tions can be proficiently and safely evaluated using

vascular imaging or left ventriculography plays an

other imaging modalities after clinical resolution of

important role in identification and differential diag-

COVID-19. Therefore, in patients with COVID-19, the

nosis of MINOCA (9). On the basis of our direct expe-

use of nuclear cardiology tests should be restricted to

rience, MINOCA accounts for >25% of ACS in patients

very specific indications when they may yield diag-

with COVID-19. Nevertheless, patient status, severity

nosis or directly influence clinical management and no

of respiratory compromise, comorbidities, and the risk

alternative imaging modalities can be performed (i.e.,

for futility should be carefully evaluated when

suspected infective endocarditis of prosthetic valves

considering indications for invasive strategies in pa-

or intracardiac devices), in order to reduce health care

tients with COVID-19.

personnel exposure related to long protocols and imaging acquisition times (45). INVASIVE CARDIAC IMAGING. When evaluating the

THE IMAGING-BASED RISK ASSESSMENT AND MONITORING

role of invasive cardiac imaging modalities in patients with COVID-19, several aspects deserve consideration.

Some clinical and laboratory risk factors for in-

In the complex rearrangement of the health care ser-

hospital death have already been identified in pa-

vice, all efforts should be directed to ensure the stan-

tients with COVID-19 (7,8). The quantification of lung

dard of care and timely access to the catheterization

and cardiac involvement by multimodality imaging

laboratory for patients with acute cardiovascular con-

could effectively delineate the severity of the disease

ditions, irrespective of SARS-CoV-2 infection. There-

and eventually the prognosis, providing a base for

fore, the use of ICA in patients with COVID-19 should be

further clinical decision making.

restricted to those presenting with clinical or hemo-

Quantification of lung damage using a chest CT

dynamic instability, including acute MI, myocarditis,

severity score has been proposed to identify patients

cardiogenic shock, and cardiac arrest (Figure 6). In

who need hospital admission (31). This score sums

these cases, an invasive strategy is pivotal to ensure

individual scores from 20 lung regions: scores of 0, 1,

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Multimodality Imaging in COVID-19

F I G U R E 6 Type 1 Acute Myocardial Infarction Complicating COVID-19 Pneumonia

A 63-year-old woman with severe COVID-19 pneumonia requiring mechanical ventilation (A) presenting hypotension, with electrocardiogram (B) showing inferior ST-segment elevation acute myocardial infarction (high-sensitivity troponin T 579 ng/l, N-terminal pro–brain natriuretic peptide 8,441 pg/ml): invasive coronary angiography (C, D) demonstrates obstructive atherosclerotic disease of the right coronary artery (arrowheads) with haziness, hinting at thrombosis of ruptured plaque (asterisk) with distal embolization to both posterior descending artery (red arrow) and posterolateral branch (white arrow).

and 2 were assigned if parenchymal opacification

the sum of regional aeration scores attributed to each

involved 0%, <50%, and $50%, respectively, of each

lung region during a standard 12-zone examination:

region (severity score range 0 to 40). The individual

0 ¼ A-lines or <3 B-lines are visualized, 1 ¼ $3 B-lines

scores for each lung as well as the total score were

involving #50% of the pleura, 2 ¼ B-lines becoming

significantly higher in patients with clinically severe

coalescent or involving >50% of the pleura, and

COVID-19 compared with mild cases. A severity

3 ¼ tissue-like pattern (33) (Figure 3). The global LUS

score <19.5 was highly effective in ruling out severe

score showed a good correlation with lung density as

COVID-19 pneumonia, with a negative predictive

assessed on CT and has been applied in the ICU

value of 96.3% (31).

setting to quantify and monitor lung aeration in

In the same way LUS could be effective in evalu-

weaning from mechanical ventilation and in patients

ating COVID-19 pneumonia severity and monitoring

with ARDS on extracorporeal membrane oxygenation

its modifications over time. For this purpose the

(33). So far, the implementation of the global LUS

numeric assessment of regional loss of aeration

score to monitor disease evolution and to guide de-

measured by global LUS score could represent a use-

cision making in patients with COVID-19 has not been

ful tool (33). The global LUS score can be calculated as

systematically investigated.

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Multimodality Imaging in COVID-19

Similarly, despite growing evidence pointing at the

paramount importance for rapid diagnosis and strat-

cardiovascular

ification. Despite its potential diagnostic utility, no

involvement in COVID-19, no specific risk scores have

unequivocal advantage has been demonstrated for an

been developed and validated. Interestingly, although

LUS-guided strategy over standard CXR and (if

great emphasis has been placed on the link between

appropriate) computed tomographic evaluation in

negative

prognostic

impact

of

myocardial injury and mortality, the actual incidence

patients with suspected or confirmed COVID-19.

of specific cardiovascular clinical conditions (myocar-

Furthermore, LUS requires closer contact with the

ditis, MI, PE, and heart failure) and the respective

patient, potentially exposing clinicians to higher risk

prognostic implications in different stages of COVID-19

for aerosolized particle inhalation, mandates the use

are largely unknown because of a significant lack of

of more protective personal protection equipment

imaging data (4). A systematic approach with the use of

(PPE), and should be performed by trained personnel.

multimodality

In this context, LUS application is a promising tech-

imaging

COVID-19-related

to

precisely

cardiovascular

characterize

manifestations

nique,

although

its

role

should

not

be

over-

should be warranted to provide clinicians with

emphasized in the absence of solid evidence; on the

comprehensive risk stratification tools.

contrary, CXR and clinical evaluation remain pivotal

APPLICATION OF IMAGING MODALITIES IN DIFFERENT CLINICAL SETTINGS

for initial patient assessment. Beyond ED evaluation, an important approach to take care of patients and prevent transmission is

Imaging modalities are useful in the management of patients with COVID-19 in different clinical settings, from triage in the ED to ICU and non-ICU wards (Figure 7).

the application of telemedicine (47). Telemedicine and e-visits could be combined with home triage for patients reporting worsening symptoms or selfmonitored

parameters,

performed

by

the

dedicated

latter

teams

being

ideally

providing

both

ED AND TRIAGE. A rapid and efficient diagnosis of

clinical evaluation and LUS at the patient’s home,

COVID-19 is of paramount importance to accurately

thus more accurately differentiating patients who

manage the large number of patients presenting to

could continue remote monitoring and medical ther-

the

apy at home from those who need hospitalization.

ED

with

suspected

SARS-CoV-2

infection.

Considering the high probability of COVID-19 among patients currently accessing ED with fever and res-

NON-ICU COVID-19 DEPARTMENT. Treatment of pa-

piratory symptoms, the main goal is to stratify pa-

tients admitted to non-ICU COVID-19 departments is

tients with positive SARS-CoV-2 RT-PCR results (or

currently based on supportive care (i.e., oxygen

with clinically highly suspected infection despite

therapy, noninvasive ventilation if necessary) and a

negative results) to discharge those with mild symp-

combination of empirically prescribed drugs (i.e.,

toms and admit to non-ICU or ICU departments those

hydroxychloroquine, antibiotic medications, antiviral

with severe or life-threatening infection. A simulta-

medications, glucocorticoid agents, and anticytokine

neous clinical evaluation and LUS performed by the

therapies). Along with clinical and laboratory evalu-

same visiting physician (reducing the number of op-

ation, imaging is fundamental to assess COVID-19

erators exposed), combined with laboratory testing

evolution and response to therapy, both in daily

and CXR, allows fast diagnosis, risk stratification, and

clinical activity and in the context of controlled

decision making regarding patient destination. In this

pharmacological and interventional trials. Baseline

context, LUS has the potential to rapidly discriminate

CT is frequently used to confirm diagnosis and to

initial

pre-

obtain detailed information on disease extent and

sentations (34). FoCUS is an adjunct to recognize

severity, thus becoming also a reference for subse-

specific ultrasound signs in patients with or sus-

quent imaging follow-up (28). Of note, considering its

pected cardiac symptoms (37). This quick stratifica-

known advantages (portability, bedside evaluation,

tion could be subsequently confirmed by CXR, trying

safety), LUS seems particularly useful for serial as-

to limit the number of computed tomographic scans

sessments during hospital stay and may be useful to

performed in the ED setting, reserving CT for cases

determine the timing of CT (34). Alongside with lung

with uncertain diagnosis or to rule out other causes of

imaging, FoCUS could be useful to assess volume

illness, such as PE. Of note, several patients have a

status

severe form at ED presentation, rapidly becoming

reserving cardiac CT, ICA, and CMR only for select

noninvasive ventilation dependent and, therefore,

cases, including suspected concomitant MI, PE, and

cannot easily undergo CT; in these patients, LUS is of

myocarditis (37).

forms

of

COVID-19

from

advanced

and

concomitant

cardiac

involvement,

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Multimodality Imaging in COVID-19

F I G U R E 7 Integrated Multimodality Imaging Pathways in Clinical Practice

Suspected COVID-19 positive SARS-CoV-2 PCR test or negative test but high clinical probability

Emergency Department

Clinical evaluation Laboratory testing Bedside imaging assessment CXR

Uncertain diagnosis or Overlapping cardiac symptoms

LUS

FoCUS

CT

Diagnosis and risk stratification

Mild disease Mild respiratory symptoms Patchy interstitial signs

Severe disease or critical conditions Oxygen-requiring or rapidly deteriorating Diffuse interstitial signs or consolidation

COVID-19 excluded

Out-of-hospital management

In-hospital management

Treat appropriately / Discharge

Telemedicine: home LUS

Non-ICU COVID-19 department

COVID-19 ICU

Baseline lung involvement assessment (consider)

Baseline lung involvement assessment

CT

CT

Volume status assessment

Respiratory disease evolution

Cardiac complications

Non-invasive hemodynamics

Bedside ECMO implantation

FoCUS

LUS

TTE / TEE

FoCUS

TEE

CXR

CT / ICA

CT

CMR

Specific multimodality imaging pathways can be implemented in different clinical settings for diagnosis, risk stratification, management, disease progression monitoring, and detection of eventual cardiovascular complications. COVID-19 ¼ coronavirus disease-2019; CMR ¼ cardiac magnetic resonance; CT ¼ computed tomography; CXR ¼ chest radiography; ECMO ¼ extracorporeal membrane oxygenation; FoCUS ¼ focused cardiac ultrasound; ICA ¼ invasive coronary angiography; ICU ¼ intensive care unit; LUS ¼ lung ultrasound; PCR ¼ polymerase chain reaction; SARS-CoV-2 ¼ severe acute respiratory syndrome-coronavirus-2; TEE ¼ transesophageal echocardiography; TTE ¼ transthoracic echocardiography.

COVID-19 ICU. The ICU represents the most chal-

changes are observed, substantial modifications in

lenging setting in the management of patients with

morphological

COVID-19. Ideally, baseline CT is needed in all criti-

ventilator-related complications need to be excluded

cally ill patients requiring ICU admission to precisely

(32). Echocardiography could be useful to rule out

describe morphological lung involvement. As in the

concomitant cardiogenic causes of respiratory mani-

previously described clinical settings, serial LUS and

festations (37). Furthermore, FoCUS allows noninva-

CXR are fundamental to monitor disease evolution in

sive hemodynamic monitoring in the ICU setting:

ICU patients, while CT could be used when clinical

assessment

of

lung

damage

biventricular

are

suspected,

function,

or

estimated

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Multimodality Imaging in COVID-19

T A B L E 4 Personal Protection Equipment Needed at Different Protection Levels During Diagnostic Examinations in Patients With COVID-19

TTE/CT/CMR Respiratory Symptoms

Protective cap

TEE/ICA

No Respiratory Symptoms

Respiratory Symptoms

No Respiratory Symptoms

X

X

X

X*

X

Surgical mask N-95/FFP2 and N-99/FFP3 respirator

X

X

X

Goggles/face shield

X

X

X

X*

X

Nonsterile gloves

X

Sterile latex gloves

X

X

Disposable plastic gown

X

X*

Isolation fluid-resistant gown

X

X

Shoe covers/protective boots

X

X

X X

*Surgical mask, nonsterile gloves, and disposable plastic gown may be used in addition to N-95/FFP2 and N-99/FFP3 respirator, sterile gloves, and isolation fluid-resistant gown, respectively, to reduce personal protective equipment contamination. TEE ¼ transesophageal echocardiography; TTE ¼ transthoracic echocardiography; other abbreviations as in Tables 1 and 2.

stroke volume, filling pressures, pulmonary pres-

proved otherwise. Optimization of the health care

sures, and central venous pressure (37). Similarly,

network and patient pathways is required to avoid

TTE helps in identifying patients at high risk for

contamination between infected patients and SARS-

ventilator weaning failure and guides tailored thera-

CoV-2-negative patients, while maintaining adequate

peutic strategy. Finally, when mechanical respiratory

health assistance. Both patients and health care

and circulation support with extracorporeal mem-

workers should be provided with standard PPE and

brane oxygenation is needed, both TTE and TEE are

keep social distance when possible. On the basis of our

important to guide device selection (venovenous vs.

experience, RT-PCR testing should be performed

venoarterial) on the basis of concomitant cardiogenic

according to local resources in select patients requir-

cause, assist during device placement (cannulation),

ing hospitalization or undergoing aerosol-generating

and monitor cardiac function and device-related

high-risk procedures, after body temperature mea-

complications during support (48).

surement

COVID-19-FREE PATIENTS. Patients with low clinical

evaluating history of fever, dyspnea, or cough and

suspicion for COVID-19 and those with negative RT-

SARS-CoV-2 exposure in recent weeks (50).

and

a

clinical

triaging

questionnaire

PCR results deserve special consideration. As medical systems are overwhelmed, an accurate balance

MANAGEMENT STRATEGY FOR CLEANING,

between infection prevention and adequate health

PROTECTION, AND DISINFECTION

care assistance delivery should be pursued. Besides clinical

disease

probability

assessment,

while

The

current

COVID-19

pandemic

has

sharply

serology tests are under development, current stra-

increased the examination work load of imaging de-

tegies to reduce in-hospital SARS-CoV-2 spread from

partments. The in-hospital infection rate was about

asymptomatic patients rely on RT-PCR nasopharyn-

41% in a Chinese experience: 29% among hospital

geal swab tests, which have important limitations

staff members and 12.3% among inpatients (2). In

(49). Therefore, adherence to international guideline

Italy, up to 9% of overall cases were reported among

recommendations and restriction of imaging tests to

health care workers, with an estimated in-hospital

those with an important impact on patients’ clinical

infection rate of 10.8% (51). SARS-CoV-2 trans-

management are advocated (35,36). Triaging pro-

mission occurs through the direct inhalation of

tocols

patients

droplets but also by touching the eyes, nose, or

requiring nondeferrable but schedulable imaging ex-

mouth after hand contact with contaminated sur-

aminations, who can be appropriately managed after

faces. Imagers, nurses, and technicians are at espe-

RT-PCR results are available, and those with urgent or

cially high risk because of close patient contact while

emergent

performing imaging studies. To prevent and mitigate

should

acute

differentiate

cardiovascular

between

conditions,

who

should be considered SARS-CoV-2 positive until

transmission,

preventive

measures

must

be

1805

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Multimodality Imaging in COVID-19

implemented,

encompassing

facilities,

imaging

equipment, PPE, and machine disinfection proced-

HIGHLIGHTS

ures (35).

 Cardiac involvement is present in up to 12% of patients with COVID-19.

Specific in-hospital routes between the imaging department and COVID-19 wards should be defined. The special environment for COVID-19-dedicated imaging should include a contaminated equipment area, a separated report room, and a staff cleaning room. The use of mobile equipment and dedicated scanners, ultrasound probes, and machines for infected patients should be encouraged (35). Staff members must undergo rigorous nosocomial infection training and be equipped with high-quality PPE (Table 4), balancing the risk for transmission

 Multimodality imaging is essential in different clinical settings in COVID-19.  Multimodality imaging is useful in diagnosis, risk stratification, and management.  Strategies for preventing viral transmission during examinations must be adopted.

with the potential for scarcity of PPE, considering in some cases their reuse, with adequate precautions. The use of a checklist and a step-by-step process to ensure proper wearing (donning) and removing (doffing) is recommended. Imaging personnel not directly involved should avoid any contact, and the distance between technicians and patients must be, preferably, >1 to 2 m. All patients should wear surgical masks during imaging. Left-lateral patient positioning with the scanner on the right side of the bench may ensure the greatest distance between the patient’s face and the echocardiographer during TTE. Personnel involved in TEE should wear full PPE, as this procedure is aerosol generating. Although a cuffed endotracheal tube and closed-circuit ventilation could reduce the risk for aerosol generation in intu-

the relevance of adequate PPE use and adherence to a rigorous safety protocol (52). Because PPE availability could be a significant issue, especially in hard-hit areas, the use of clinical judgment should be emphasized

to

avoid

additional

staff

exposure

deriving from performing imaging tests unlikely to yield clinically important information among COVID19-positive or suspected positive patients. Thus, the need for procedures requiring stringent PPE (i.e., TEE or nuclear imaging) and the possibility to perform alternative imaging modalities (i.e., cardiac CT) or no procedure at all should be thoroughly assessed in order to optimize PPE use.

bated patients, noninvasive ventilation carries a higher risk for droplet spreading. The level of pro-

CONCLUSIONS

tection during TEE should be full in both the ICU and the non-ICU context (35).

The

SARS-CoV-2

outbreak

has

rapidly

reached

Because SARS-CoV-2 is sensitive to most standard

pandemic proportions and has become a major threat

viricidal disinfectant solutions, imaging machines

to global health. Although the predominant clinical

should be thoroughly cleaned. It is recommended to

feature of COVID-19 is an acute respiratory syndrome

use soft cloth dipped in 2,000 mg/l chlorine-

of varying severity, the cardiovascular system can be

containing disinfectant or 75% ethanol for scanners

involved in several ways. Heart and lung multi-

disinfection (35). Generally, for echocardiographic

modality imaging plays a central role in different

probes, it is advised to immerse them for #1 h

clinical settings and is essential in diagnosis, risk

without using hot steam, cold gas, or abrasive

stratification, and management of patients with

agents, such as ethylene-oxide or glutaraldehyde-

COVID-19. To prevent and mitigate transmission, key

based methods. Automated disinfection solutions

preventive measures must be adopted, encompassing

should be available. Air, object surfaces, and floor

equipment, facilities, health care personnel, and

disinfection

disinfection procedures.

in

the

COVID-19-dedicated

imaging

department should be carried out according to daily operation specifications. In reading rooms, social distancing should be remembered and all nones-

ADDRESS FOR CORRESPONDENCE: Dr. Eustachio

sential items removed (35).

Agricola,

Cardiovascular

Imaging

Unit,

Cardio-

As of this writing, none of the health care workers

Thoracic-Vascular Department, San Raffaele Scienti-

in the cardiac imaging department of our hospital

fic Institute, Via Olgettina 60, 20132 Milan, Italy.

have been infected with SARS-CoV-2, underscoring

E-mail: [email protected].

Agricola et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 13, NO. 8, 2020 AUGUST 2020:1792–808

Multimodality Imaging in COVID-19

PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: To

of COVID-19 patients. To select the proper personal

recognize COVID-19 pathogenesis, pulmonary and car-

protection equipment for health care workers protection

diovascular clinical manifestations, and the corresponding

during imaging examinations in COVID-19 era.

imaging findings in order to improve patient care.

TRANSLATIONAL OUTLOOK: A systematic multimo-

COMPETENCY IN PATIENT CARE AND

dality imaging approach to COVID-19-related cardiovas-

PROCEDURAL SKILLS: To apply integrated heart and

cular manifestations could provide clinicians with

lung multimodality imaging in different clinical settings

comprehensive tools for risk stratification and decision

to improve diagnosis, risk stratification, and management

making.

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KEY WORDS cardiac magnetic resonance, chest x-ray, computed tomography, coronavirus, COVID-19, echocardiography, lung ultrasound, multimodality imaging, SARS-CoV-2

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