key: cord-1006136-nhsn4cru authors: Cameli, Matteo; Pastore, Maria Concetta; Soliman Aboumarie, Hatem; Mandoli, Giulia Elena; D'Ascenzi, Flavio; Cameli, Paolo; Bigio, Elisa; Franchi, Federico; Mondillo, Sergio; Valente, Serafina title: Usefulness of echocardiography to detect cardiac involvement in COVID‐19 patients date: 2020-07-12 journal: Echocardiography DOI: 10.1111/echo.14779 sha: da0f9317ba27dc73abc3f86fb72668327dd0e20b doc_id: 1006136 cord_uid: nhsn4cru Coronavirus disease 2019 (COVID‐19) outbreak is a current global healthcare burden, leading to the life‐threatening severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, evidence showed that, even if the prevalence of COVID‐19 damage consists in pulmonary lesions and symptoms, it could also affect other organs, such as heart, liver, and spleen. Particularly, some infected patients refer to the emergency department for cardiovascular symptoms, and around 10% of COVID‐19 victims had finally developed heart injury. Therefore, the use of echocardiography, according to the safety local protocols and ensuring the use of personal protective equipment, could be useful firstly to discriminate between primary cardiac disease or COVID‐19–related myocardial damage, and then for assessing and monitoring COVID‐19 cardiovascular complications: acute myocarditis and arrhythmias, acute heart failure, sepsis‐induced myocardial impairment, and right ventricular failure derived from treatment with high‐pressure mechanical ventilation. The present review aims to enlighten the applications of transthoracic echocardiography for the diagnostic and therapeutic management of myocardial damage in COVID‐19 patients. postmortem examination of 3 COVID-19 victims. 7 In two studies by Shi et al 8 and Guo et al, 9 among 460 and 187 patients hospitalized for COVID-19, respectively, 20% and 28% had acute myocardial injury, which was associated with higher mortality and incidence of complications, such as acute respiratory distress syndrome (ARDS), malignant arrhythmias, acute renal injury, and coagulopathy. Echocardiography is considered the first-choice diagnostic technique for the evaluation of myocardial structure and function, due to its high availability and cost-effectiveness. 10 For this reason, a conscious inhospital application of transthoracic echocardiography (TTE), using a focused and safe approach, according to the latest European Association of Cardiovascular Imaging (EACVI) and American Society of Echocardiography (ASE) recommendations, 11, 12 could reduce the potential risks of COVID-19 heart injury, providing early detection and treatment. These documents do not provide strict indications on whether to perform or reject an echocardiographic examination in this period of social distancing, since it should be tailored on the single patient, trying to avoid unnecessary exam- Guidance for COVID-19 suggests that patients demonstrating HF, arrhythmia, electrocardiographic (ECG) changes, or cardiomegaly should undergo echocardiography. 13 As reported by the National Health Commission of China (NHC), some of the confirmed cases of SARS-CoV-2 patients first showed cardiovascular rather than respiratory symptoms. 9 After the nasal or pharyngeal swab has done to test COVID-19 patients' status before the admission 14 , the first step of triaging usually comprises ECG and blood cardiac enzymes dosage; however, evidence has shown that troponin and brain natriuretic peptide (BNP) levels could increase due to COVID-19 itself, proportionally to the severity of the disease. 9 In fact, a meta-analysis showed that troponin I values were significantly higher in patients with severe compared to those with mild illness due to SARS-CoV-2 infection. 15 He et al conducted a study in critical COVID-19 patients dividing them into two groups according to the presence (24 patients, 44.4%) or absence (30 patients, 55 .6%) of myocardial injury, revealing that the injury group presented significantly higher inhospital mortality (75.0% [18/24] vs. 26.7% [8/30] , P = .001), C-reactive protein (CRP), and N-terminal pro-BNP (NT-pro-BNP, P < .01). 6 Chen Chen et al also analyzed 150 COVID-19 subjects and found 22 of them (14.7%) having troponin elevation, which was independently correlated with COVID-19 critical severity with multivariate regression analysis (odds ratio, OR = 26.909, 95% CI 4.086-177.226, P = .001). 16 Accordingly, ACC COVID-19 clinical guidance pointed out that that classic symptoms and presentation of acute myocardial infarction may be unclear in the context of COVID-19, resulting in underdiagnosis. 13 Moreover, in a small Italian report of 28 COVID-19 patients with ST-elevation myocardial infarction (STEMI), 78.6% of them presented with acute chest pain, while 82.1% had regional wall-motion abnormalities at TTE. 17 In fact, echocardiography could support diagnosis in this setting, revealing suggestive signs of acute myocardial infarction, new-onset or worsening congestive HF, pericardial effusion or tamponade, and RV overload due to pulmonary embolism or cor pulmonale (Table 1 ). This would lead to an accurate triaging, ensuring each patient the appropriate treatment. Various degrees of myocardial injury (defined as raised troponin levels over the 99th percentile of reference range) have been recently shown in patients with COVID-19. 18, 19 In a clinical study involving 138 patients with COVID-19, 10 patients (7.2%) had acute myocardial injury 20 and 23 (16.7%) had arrhythmia, the majority of them during hospitalization in intensive care unit (ICU). There are many possible causes of acute myocardial injury in critically ill patients, including acute coronary syndrome, HF, myocarditis, hypotension or shock, sepsis, and infection. To date, the mechanism responsible of myocardial injury in COVID-19 is uncertain; however, hypothesis has focused on local or systemic immune response, possibly causing cardiomyocytes degeneration and/or microvascular thrombosis. 21 Accordingly, current reports suggest that the majority of COVID-19 patients with myocardial injury without evidence of epicardial coronary artery thrombosis, show imaging data supporting the diagnosis of acute myocarditis 21, 22 ; also, cases of fulminant myocarditis and fatal arrhythmias have been described. 23, 24 Even if a direct cardiotropic localization SARS-CoV-2 into myocytes has never been demonstrated, some authors showed autoptic findings (eg, lymphocyte infiltrates and macrophagic response) compatible with viral myocarditis. [25] [26] [27] Moreover, in a retrospective study by Ruan et al evaluating factors associated with mortality in 150 COVID-19 subjects, patients who died showed higher levels of troponin, myoglobin, C-reactive protein, serum ferritin, and interleukin-6, suggesting a high inflammatory burden in COVID-19 with a possible rise in myocarditis-related cardiac events. 28 For acute myocarditis, a combination of cardiac magnetic resonance (CMR) and myocardial biopsy is the reference diagnostic method, 29 preceded by coronary angiography to rule out acute coronary syndromes. This is also valid for COVID-19 patients. Accordingly, Inciardi et al presented a case of a 53-year COVID-19 woman who developed acute myocarditis diagnosed, after exclusion of coronary disease and TTE findings consistent with acute myocarditis (increased wall thickness, diffuse echo-bright myocardial appearance and diffuse LV hypokinesis, with LVEF 40%), by CMR as increased wall thickness with diffuse biventricular hypokinesis and signs of marked biventricular myocardial interstitial edema by T2mapping sequences and late gadolinium enhancement. 22 However, in critical patients and in this reduced healthcare services emergency status, CMR and myocardial biopsy could not be promptly available and coronary angiography would put unstable patients at higher risks. Therefore, an echocardiographic study could be used as the first investigation tool to orient diagnosis with high-sensitive but less specific findings, that are listed in Table 2 . 30 Additionally, LV longitudinal strain proved to correlate with myocardial edema detected by CMR in patients with acute myocarditis 31 and its bull's eye representation shows the localization of myocardial damage, with GLS typically reducing from endocardial to epicardial layer ( Figure 1 ). In patients with COVID-19, cardiovascular involvement leading to cardiac dysfunction and failure is not uncommon, probably due to systemic inflammatory response, innate immune-related myocardial damage, or respiratory-induced hypoxemia during COVID-19 progression. 16, 32 This also affects patients without history of chronic HF, which could rapidly develop severe HF and die for sudden cardiac death after COVID-19 infection. In fact, the most likely mechanism of HF in these patients is consequent to lung tance devices, such as intra-aortic balloon pump, could be necessary to assist hemodynamics and improve outcome. 9 Therefore, focused but thorough and, if necessary, repeat ultrasound examination is important in COVID-19 patients with possible or overt HF not only for diagnosis and prognosis, but also to assess patients' clinical status and response to therapy ( Figure 2 ). In a recent study by Zhou et al involving 191 COVID-19 subjects, a half of their patients finally developed sepsis at a median of 9 days. In particular, sepsis was the most frequently observed complication, followed by respiratory failure, ARDS, HF, and septic shock. 45 Sepsis is caused by exaggerate host response to infection leading to life-threatening multiorgan failure (MOF), recognized with altered mental status, difficult or fast breathing, low oxygen saturation, reduced urine output, fast heart rate, weak pulse, cold extremities, or low blood pressure. This could lead to septic shock, that is persisting hypotension despite volume resuscitation and hemodynamic instability requiring vasopressor treatment. 46 The first diagnostic approach could be done with sequential organ failure assessment (SOFA) score, which is a good diagnostic marker for sepsis and septic shock, reflecting the degree of MOF. 47 However, several authors investigated the role of echocardiography for the study of septic shock, which could offer important information on cardiac loss of function due to sepsis. It has been shown that in these patients a certain grade of diastolic dysfunction could be detected by power and tissue Doppler imaging (TDI): The most used parameter is transmitral E/E′ ratio, with a lack of defined cutoff value; however, a higher proportion of diastolic dysfunction with values of E′ < 8-10 cm/s was found to be independently associated with higher risk of death 48 The use of echocardiography in this clinical setting could help clinicians in early recognizing myocardial damage due to COVIDderived sepsis. According to common ARDS management, 52 patients, 17% of patients required mechanical ventilation, 97% of whom died. 45 Whether it was due to the end-stage disease or to ventilation-induced heart and/or lung complications is not known. However, further evidence on this topic is timely needed in order improve the therapeutic management of COVID-19 patients. Transesophageal echocardiography (TOE) has been widely used for monitoring ventilated patients in the last years. In fact, in these patients TTE is often challenging, due to the position of patients with lower mobility, and the poor acoustic window due to hyperinflated lungs. However, the development of new indices for the assessment of LV systolic/diastolic function and filling pressures by TDI, and of RV dimension and function, have led to reconsider the use of serial TTE for noninvasive monitoring of ventilated patients. 61 Thanks to the widespread use of echocardiography in ICU, RV dimension and function could be closely monitored in these patients. 62, 63 As Repessé et al suggested, a RV-driven adjustment of PEEP levels could help intensivists to find a balance between risks and benefits of this therapeutic approach (ie, lung recruitment and overdistension), 56 thus preventing early mortality for ventilation-induced RV failure. LU could be an important ally also in this context. 64 In addition, RV myocardial performance index (RV MPI), also known as "Tei index" determined on trans-tricuspid velocities by pulsed wave or tissue Doppler imaging, is a high-sensitive index for the diagnosis of RV dysfunction. 65 Due to the need of balancing between risks of contagion for and benefits for patients, the common indications and modalities to perform echocardiography should be reconsidered in COVID-19 patients; therefore, the choices for the use of portable devices and transesophageal echocardiography should be tailored on the single patients depending on his clinical status and cardiovascular conditions. Portable machines have the advantage to be easier to clean and to cover than common echocardiographic machines and could be preferred for a basic assessment of biventricular function, valvular disease, and pericardial effusion. 13 However, in patients with suspected or known cardiac impairment or in uncertain clinical cases, the quality of the TTE evaluation could be sacrificed using portable echocardiographers. As an alternative, we propose the use of a dedicated echocardiographic machine in COVID units which should also be sanitized after use, thus combining safety and effectiveness. In addition, for difficult cases or severe cardiac dysfunction, we suggest performing a comprehensive image acquisition with offline measurement of complex and advanced parameters in a safe environment and at clinician time discretion, in order to obtain a complete echocardiographic examination reducing the time of exposure to SARS-CoV-2. 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