Echocardiography and Multimodality Cardiac Imaging in COVID-19 Patients.

The pandemic caused by the new SARS-CoV-2, named coronavirus disease 2019 (COVID-19) disease, has challenged the health-care systems and raised new diagnostic pathways and safety issues for cardiac imagers. Myocardial injury may complicate COVID-19 infection in more than a quarter of patients and due to the wide a range of possible insults, cardiac imaging plays a crucial diagnostic and prognostic role. There is still little evidence regarding the best-imaging pathway and the echocardiographic findings. Most of the data derive from the single centers experiences and case-reports; therefore, our review reflects the recommendations mainly based on expert opinion. Moreover, knowledge is constantly evolving. The health-care system and physicians are called to reorganize the diagnostic pathways to minimize the possibility of spreading the infection. Thus a rapid, bedside, ultrasound assessment of the heart, chest, and leg veins by point-of-care ultrasound seems to be the first-line tool of the fight against the SARS-CoV-2. A second Level of cardiac imaging is appropriate when the result may guide decision-making or may be life-saving. Dedicated scanners should be used and special pathways should be reserved for these patients. The current knowledge on cardiac imaging COVID-19 patients is reviewed. Copyright:

INTRODUCTION

The pandemic caused by the new SARS-CoV-2, named coronavirus disease 2019 (COVID-19) disease, has challenged the health-care systems and raised new diagnostic pathways and safety issues for cardiac imagers.[1] After the first stage of viral replication, with flu-like symptoms, 20% of the patients present the second phase of the disease with an exaggerated immunological response, a cytokine storm, with severe lung inflammation, with frequent cardiovascular involvement, that may lead to multiorgan failure, shock, and death.[2] Patients affected by preexisting heart disease are at high risk of complications and mortality.[3] An echocardiographic examination is commonly required to rule out the presence of cardiac injury, mainly secondary to a “cytokine storm,” acute respiratory distress syndrome (ARDS), pulmonary embolism (PE), or shock; myocardial infarction (MI) or myocarditis may be suspected in some cases. Consequently, echo imagers are frequently exposed to the risk of infection.

The Italian Society of Echocardiography and Cardiovascular Imaging was the first Scientific Society to publish, on March 15, a document underlying the importance to ensure practitioners safety, followed by other societies.[45]

There are still very few data on the echocardiographic features of the acute myocardial injury secondary to the SARS-CoV-2 infection and data must be derived from the single-center experiences and case reports.

In such patients, echocardiography is an easier tool to identify acute myocardial injury, whereas logistic and sanitizing problems limit the use of cardiac magnetic resonance (CMR) and in some cases, of cardiac computed tomography (CCT).

CARDIAC INVOLVEMENT IN COVID-19 AND IMAGING

Increased levels of troponin

Myocardial damage is a common complication of COVID-19 infection that has been reported in 7%–28% of hospitalized patients. Studies reporting the prevalence of troponin increase are summarized in Table 1.[678] Most of them lack a multivariate analysis, but a correlation between troponin increases, the respiratory insufficiency degree, and mortality is evident. Shi et al. performed a retrospective study on 416 COVID-19 patients from Wuhan with a multivariate analysis: Those with acute myocardial injury (defined as troponin I elevation level regardless to electrocardiogram and echocardiographic findings) had a higher need for noninvasive and invasive mechanical ventilation and other complications such as anemia, ARDS, acute kidney injury, hypoproteinemia, and coagulation disorders.[7] The variables independently correlated with mortality were the presence of ARDS and increased level of troponin. The mortality rate is correlated with the magnitude of the reference value of high-sensitivity troponin I levels.[79] Mild troponin elevation, i.e., 2–4-fold the upper normal value, is common in Type 2 MI, in acute heart failure, arrhythmias or PE, whereas a higher increase of troponin level, i.e., more than five times above the upper normal limit, suggests the probability of Type 1 MI, shock, Takotsubo syndrome, or myocarditis.[71011]

Table 1

Studies reporting an increased level of troponin in coronavirus disease 2019 patients

Author	n	ICU (%)	↑Troponin (%)	Shock (%)	NIV (%)	IOT (%)	Mortality (%)	Reference
Huang	41	32	12	7	24	5	15	[5]
Chen	99	23	-	4	13	4	11	[42]
Wang	138	26	7	9	11	12	-	[7]
Guan	1.099	-	-	1	5.1	2.3	1	[43]
Yang	52	100	23	35	55.8	42.3	62	[44]
Zhou	191	26	17	20	14	17	28	[9]
Shi	416	-	19.7	-	12.3	7.7	13.7	[6]
Guo	187	-	28	-	-	-	23	[9]

ICU=Intensive care units, NIV=Noninvasive ventilation, IMV=Invasive Mechanical Ventilation

Elderly patients, and those affected by copathologies, such as arterial hypertension, diabetes, previous stroke, and coronary artery disease, are more likely to be infected by SARS-CoV-2 and manifest a more severe respiratory impairment. Patients with ischemic heart disease or heart failure are more susceptible to cardiac injury and correlated to pneumonia severity, to myocardial ischemia, ventricular dysfunction, and arrhythmias, and a fatal deterioration can suddenly occur.[3] Moreover, systemic inflammation may cause coronary vasculitis, facilitate atherosclerotic plaque rupture, and enhance platelet activation leading to a Type 1 MI.[7] In these cases, the echocardiographic findings are the typical regional contractility dysfunction in a coronary territory. The cardiac imager should possibly be aware of the previous echocardiographic characteristics of those patients with a history of cardiac heart disease to correctly evaluate the actual parameters and contractility comparing them with previously available data. It has been observed a substantial increase in case fatality and complication rates during the pandemic, and this was mainly related to late arrival and admission of patients with acute coronary syndromes.[12] Severe systolic dysfunction, aneurysms, mechanical complications, and left ventricular (LV) thrombi may be easily detected with point of care echo thus rapidly suggesting the ideal medical or surgical treatment.

A Type 2 MI, in advanced stages of the disease, is more common[678] and may be secondary to hypoxia, sepsis, cytokine storm, heart failure, severe hypotension or shock, PE, stress cardiomyopathy, anemia, acute kidney failure. Indeed, MI with Non-Obstructive Coronary Arteries (MINOCA) seems to be the most frequent cause of acute coronary syndrome in COVID-19 patients.[13] Interestingly, an increased prevalence of Kawasaki-like coronaritis has been reported as an emerging complication during the COVID-19 pandemic in children.[14] Kawasaki himself in 1967 suspected that a coronavirus could be the cause of the syndrome that took his name.[15] About 2% of cases occur in the pediatric population,[16] and therefore, the cardiac imager should explore the coronaries in children affected or suspected to have contracted the disease.

MYOCARDITIS

The presence of the angiotensin-converting enzyme 2 receptor in the myocardial cells represent the potential door-of-entry of SARS-CoV-2 within cardiomyocytes with an internalization process similar to SARS-CoV-1.[17] Whether SARS-CoV-2 may cause acute direct myocarditis, however, is still a matter of debate. Single case reports have been published, but the presence of the viral genome inside the myocardial cells has not yet been demonstrated. Cases of “fulminant myocarditis” have been described.[1819] In an Italian case report of a 53-year-old woman without known cardiovascular disease and increased troponin levels, transthoracic echocardiography showed normal LV dimensions with thickened and echo-brightened walls, diffuse hypokinesia with severe systolic and diastolic dysfunction and a circumferential pericardial effusion.[20] These signs are commonly found in acute myopericarditis, and there is no reason to suppose that the typical echocardiographic findings should differ from any other viral myocarditis and/or pericarditis. However, an endomyocardial biopsy has been performed only in two case-reports:[2122] Sala et al. reported a diffuse T-lymphocytic inflammatory infiltrates and interstitial edema, but the absence of the SARS-CoV-2 genome within the myocardium, whereas Tavazzi et al. found the viral particles within the interstitial but not inside the myocardial cells.

Table 2 summarizes the reported cases: In none of them, the viral RNA has been detected inside the myocardial cells, therefore a definite diagnosis, according to the current European Society of Cardiology guidelines,[23] cannot be made.[24] A clinical scenario of myocarditis, sometimes “fulminant,” may be present but the cytokine storm itself may cause a myocardial injury whose clinical signs are not distinguishable from other myocarditis etiologies [Figure 1].

Table 2

Studies reporting suspected myocarditis in coronavirus disease 2019 patients

Author	N. cases	Age (year)	Male/female	Myocardial histology	Outcome	Reference
Zeng	1	63	Male	No	Death on the 33rd day of hospitalization	[17]
Hu	1	37	Male	No	Good with corticosteroids and immunoglobulins	[18]
Inciardi	1	53	Female	No	Stabilization after dobutamine, lopinavir/ritonavir	[19]
Sala	1	43	Female	Yes	Good with lopinavir/ritonavir and hydroxychloroquine	[21]
Tavazzi	1	69	Male	Yes	VA-ECMO as a bridge to recovery	[20]
Barton	2 autoptic	77,42	Male, male	Histology not shown	Acute ischemic injury in 1	[39]
Tian	4 autoptic	78,74,81,59	Female, male, male, male	Histology not shown	Focal mild edema, interstitial fibrosis and myocardial hypertrophy; no inflammatory cellular infiltration	[40]
Varga	2 autoptic	71,58	Male and female	Histology not shown	Not described	[41]
Xu	1 autoptic	50	Male	Histology shown	Few interstitial mononuclear inflammatory infiltrates but no other substantial damage	[42]

VA-ECMO=Venoarterial extracorporeal membrane oxygenation

Figure 1

Case of cardiogenic shock in a 45 yo COVID-19 man and high hs-troponin levels suggesting possible “fulminant myocarditis”. (a): Three-fascicular block in ECG. (b) hemodynamic parameters show low arterial pressure and cardiac index, high systemic vascular resistance index, low global end diastolic index and increased extravascular lung water index. (c and d) Echocardiographic five and three-chamber views showing concentric hypertrophy or “pseudo”-hypertrophy due to myocardial edema with reduced left ventricular volume and systolic function (frame from Video 3)

Similar to the previous 2003 SARS-CoV-1 epidemic, an impairment of LV systolic and/or diastolic function, often reversible, and sometimes subclinical, seems to be common, even among those patients without preexisting heart disease. A sepsis-induced-cardiomyopathy with severe diffuse contractility impairment may be present.[25]

ECHOCARDIOGRAPHY AND ARDS

In hospitalized patients, COVID-19 may be complicated by ARDS in 19.6%–41.8% of the cases.[310] In these cases, a right ventricular dysfunction (RVD) is frequently present, and it has been demonstrated to predict the mortality.[2627] Echocardiography is the best diagnostic tool to evaluate the presence and degree of RVD. A multiparametric evaluation is mandatory and requires an advanced level of competence. Due to the imaging difficulties in ARDS-ventilated patients, with a frequent absence of transthoracic windows, a trans-esophageal echocardiography (TEE) would be the best-imaging modality. A TEE may be performed even in the prone position, and it adds information on the presence of a right-to-left shunt across a patent foramen ovale, a condition that imagers are frequently asked to rule-out in this setting.[28] The appropriateness of the TEE should be always discussed, and the TEE examination performed only when required for decision-making, such as in cases of mechanical ventilation weaning difficulties due to a suspected cardiac dysfunction.

PULMONARY EMBOLISM

There is evidence of a link between thrombotic events such as PE and COVID-19.[2930] The cytokine storm induces a defective procoagulant/anticoagulant balance thus predisposing to deep veins thrombosis, microthrombi, and disseminated intravascular coagulation in severe cases. The raised d-dimer concentrations is a poor prognostic feature and a mortality risk factor.[10] Passive inactivity contributes to the thrombo-embolic risk. The logistic difficulties to perform a CT scan to confirm the suspect of PE, with consequent need of sanitation, may increase the role of ultrasound diagnosis, especially in the emergency conditions. The echocardiographer should be aware of the low sensitivity of echocardiography alone in the diagnosis of PE, of the possibility of pre-existing heart and respiratory disease, and that RV dysfunction is frequently secondary to ARDS in ventilated COVID-19 patients, rather than to a PE. A sign that could be is useful is the preserved RV apex contractility in PE (McConnell sign),[31] whereas in acute cor pulmonare secondary to ARDS the hypokinesia is diffuse. This sign has a 77% sensitivity and a 94% specificity for the diagnosis of acute PE, with a negative predictive value of 96%.

Multiorgan ultrasonography, the concomitant use of heart, lung, and ultrasound increase, (named “Triple Pocus”), increases the ultrasound diagnostic sensitivity up to 90% and a specificity of 86.2%[32] and should always performed [Figure 2].

Figure 2

Ultrasound diagnosis of pulmonary embolism treated with thrombolysis in a COVID-19 patient who underwent a cardiac arrest due to pulseless electrical activity. (a) Venous Ultrasound showing a deep femoral vein thrombosis. (b) Echocardiographic long-axis view showing a right ventricle enlargement and dysfunction. (C) Echocardiographic sub-xifoideal view showing a right ventricle enlargement and dysfunction (frame of Video 2). (d) After thrombolysis the echocardiographic long-axis view shows a right ventricle enlargement and dysfunction recovery which is confirmed by the sub-xifoideal approach (e)

Pulmonary hypertension is another issue. Some patients, after the acute phase, may develop an interstitial fibrosis whose the long-term follow-up is still unknown. Signs of right RV dilatation, RV dysfunction, and an estimate of pulmonary hypertension are the fundamental parameters for cardiac imagers, and should be monitored in the follow-up.

An appropriate use of echocardiography in every setting should be advocated, from the emergency department to the intensive care unit (ICU) and after discharge from the hospital, in patients with persistent effort dyspnea to evaluate and monitor the follow-up. An early identification of pulmonary hypertension, or any other cardiac abnormalities, can improve the clinical course, and help the scientific community in better understanding the long-term outcomes of recovered patients.

APPROPRIATENESS OF ECHOCARDIOGRAPHY IN COVID-19 PATIENTS

The decision pathway for echocardiographic imaging has to be refocused according to the need of avoiding any risk of contamination. Both the European Association of Echocardiography and Cardiovascular Imaging (EACVI)[5] and the American Society of Echocardiography (ASE)[4] produced recommendation documents.

A systematic use of echocardiography is inappropriate in the diagnostic phase, and the prognostic stratification. Asymptomatic patients, or with mild, influenza-like symptoms (i.e., not hospitalized,) do not need to undergone an echocardiographic examination. On the contrary, a transthoracic echo is important in the follow-up of hospitalized patients affected by the multiple area of pneumonitis consolidations, in ARDS and complicated patients. Table 3 summarizes the main indications. Patients with a suspected myocardial damage, due to ischemic electrocardiographic changes, or increased troponin levels, arrhythmias, unexplained hypotension or shock, suspected PE, difficulties to ventilation weaning are common indication in ICUs. Suspected pericardial effusion or infective endocarditis, in case of superimposed bacterial infections, a not uncommon condition in prolonged mechanical ventilated patients, are other possible indications.

Table 3

Appropriateness of echocardiography in coronavirus disease-2019 patients

IMAGING MODALITY

A dedicated echocardiographic scanner should be present in COVID-19 settings, both medical and ICU, to avoid logistic and sanitizing problems.

A dedicated cardiac imager should be present day and night, with at least the expertise to perform a point of care ultrasound (POCUS) or focused examination, including transthoracic, echocardiography, and venous ultrasound.[33] Such a “multimodality echo one-step approach” is of crucial importance in COVID-19 patients to achieve in a single step all the diagnostic and prognostic information.

When a dedicated scanner and/or an imager cannot be present 24 h a day, and the imager has to get in the COVID-area to perform the echo, the appropriateness should be discussed, and the imager should suggest the best diagnostic pathway for the patient, according to clinical status, performing only the examinations which are regarded essential for decision-making. Experienced operators are advocated due to the complexity of the pathologies, and the technical difficulties in obtaining good quality images. A new organizational model of remote consulting could be implemented, allowing, beyond protection from the risk of infection, the opportunity to exchange skills and experiences with mutual cultural enrichment.

Personal protective equipment should be used according to the risk level according to Institutional and current recommendations. The exam should be as fast as possible, and focused on the clinical indication, performed at bedside; still images and videos should be achieved rapidly, then interpreted and measured offline in a noninfected area. Less experienced echocardiographers may send images or discuss them using appropriate video-consult equipment. Archiving images is essential to review and compare them with future examinations in the same patient.

In ventilated patients the quality of imaging is often sub-optimal for several reasons: They are dyspneic, in supine and sometimes prone position, high positive end expiratory pressures are often used; low-quality portable ultrasound systems are employed.

In COVID-19 patients with ARDS, prone ventilation is used for the recruitment of alveoli to improve oxygenation.[34] In such position, the posterior views may be used. In a normal condition, the aerated lung is a barrier to ultrasound and the heart is not visible, on the contrary, in the presence of a pleural effusion and/or of a lung consolidation, positioning the probe on the posterior left chest wall may allow to explore heart views;[35] moreover, from a right posterior view, the inferior vena cava diameter and collapsibility are easily explored,[36] [Figure 3].

Figure 3

Ecocardiographic posterior views in COVID-19 patient. (a) Chest X-ray with multiple, bilateral and diffuse peripheral opacities. (b) CT scan with bilateral, subpleural opacities, septal thickening, air space consolidations and pleural effusion. (c-e) Ecocardiographic left posterior views showing, through pleural and pericardial effusion and parenchimal consolidation, left ventricle in short axis (diastolic frame of Video 1). (e) Systolic frame of same video. (d) Left posterior view in another case of large pleural effusion. (f) Right posterior view showing inferior vena cava collapsibility

In such patients, TEE would undoubtedly allow higher sensitivity with the mandatory use of the appropriate PPE, and a dedicated ultrasound machine and probe.

MULTIMODALITY IMAGING

First of all, a multimodality echo approach is mandatory. Echocardiography, chest echography, and venous ultrasound (the triple POCUS Approach) should be performed.

CARDIAC MAGNETIC RESONANCE

A suspected myocarditis or myopericarditis, and a MINOCA, are common appropriate indications for CMR which add fundamental diagnostic and prognostic information. Unfortunately, the feasibility of a CMR in COVID-19 patients is low, unless there is a disposable dedicated scanner, which is uncommon at present time.

The EACVI[37] and the Society of CMR (https://scmr.org/page/COVID19) developed recommendations which can be summarized as follows:

The exam should be performed only if absolutely clinically necessary and the appropriateness must discussed with the ordering physician. If no other imaging modality is presumed to rule out the decision pathway, the exam should be targeted, using shortened protocols and focusing the clinical question. Studies can often be safely deferred after the healing, such in cases of a suspected myocardial injury to evaluate the presence, site and extension of fibrosis. A special care should be paid before administration of contrast agent as the renal function is often altered in COVID-19 patients and the contrast could be contraindicated.

CARDIAC-COMPUTED TOMOGRAPHY

Similar rules should be applied for CCT. A dedicated scanner should be present and a dedicated pathway planned. In this section we will summarize some diagnostic issues that may be important in this setting. In patients with increased troponin levels, in whom an acute coronary syndrome is suspected, a coronary CCT scan may be preferred to an invasive strategy, as in most cases a Type 2 MI is present without significant coronary lesions and the negative predictive value of the exam is very high. A Takotsubo syndrome may be evaluated acquiring CCT cine imaging of the ventricle contractility.[22]

In myocarditis the presence and distribution of Late Contrast Enhancement can be detected, and have a similar clinical significance, as commonly detected by CMR.[3738]

In case of PE the hemodynamic information necessary for risk stratification and guiding therapy can be achieved measuring from the CT scan the RV degree of dilatation and the right to left ventricular ratio,[3940414243444546] avoiding the need of ultrasound.

In patients affected by atrial fibrillation or flutter, not uncommon arrhythmias in these patients, when a TEE cannot be performed, the presence of an appendage thrombosis may be ruled out by CCT [Figure 4]. Finally, in COVID-19 patients suspected to have an infective endocarditis, a positron emission tomography-fluorodeoxyglucose or a CCT scan may be a valid diagnostic alternative to overcome the logistic feasibility of a TEE study.

Figure 4

Computed tomography scan showing a right (a) and Left (b) appendage thrombosis

CONCLUSION

Myocardial injury may complicate COVID-19 infection in more than a quarter of patients and due to the wide a range of possible insults, cardiac imaging plays a crucial diagnostic and prognostic role. There is still little evidence regarding the best-imaging pathway and the echocardiographic findings. Most of the data derive from single centers experiences and case-reports; therefore, our review reflects the recommendations mainly based on the expert opinion. Moreover, knowledge is constantly evolving. The health-care system and physicians are called to reorganize the diagnostic pathways to minimize the possibility of spreading the infection. Thus, a rapid, bedside, ultrasound assessment of the heart, chest, and leg veins by point-of-care ultrasound seems to be the first-line tool of the fight. Large scale registries and studies are needed to understand the independent prognostic role of cardiac injury and of the echocardiographic quantitative parameters involving both the old and the new technologies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.