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Canadian Journal of Cardiology

The Utility of Handheld Cardiac and Lung Ultrasound in Predicting Outcomes of Hospitalised Patients With COVID-19

  • Author Footnotes
    ‡ Drs Dadon and Levi contributed equally to this work.
    Ziv Dadon
    Footnotes
    ‡ Drs Dadon and Levi contributed equally to this work.
    Affiliations
    Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel
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  • Author Footnotes
    ‡ Drs Dadon and Levi contributed equally to this work.
    Nir Levi
    Footnotes
    ‡ Drs Dadon and Levi contributed equally to this work.
    Affiliations
    Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel
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  • Amir Orlev
    Affiliations
    Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel
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  • Daniel Belman
    Affiliations
    Intensive Care Unit, Shaare Zedek Medical Center, Jerusalem, Israel
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  • Evan Avraham Alpert
    Affiliations
    Emergency Department, Shaare Zedek Medical Center, Jerusalem, Israel

    Faculty of Medicine Hebrew University, Jerusalem, Israel
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  • Michael Glikson
    Affiliations
    Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel

    Faculty of Medicine Hebrew University, Jerusalem, Israel
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  • Author Footnotes
    § Drs Gottlieb and Butnaru contributed equally to this work.
    Shmuel Gottlieb
    Correspondence
    Corresponding author: Dr Shmuel Gottlieb, Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Shmu’el-Bait St 12, Jerusalem, 9103102, Israel. Tel.: +972-26555975.
    Footnotes
    § Drs Gottlieb and Butnaru contributed equally to this work.
    Affiliations
    Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Author Footnotes
    § Drs Gottlieb and Butnaru contributed equally to this work.
    Adi Butnaru
    Footnotes
    § Drs Gottlieb and Butnaru contributed equally to this work.
    Affiliations
    Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel
    Search for articles by this author
  • Author Footnotes
    ‡ Drs Dadon and Levi contributed equally to this work.
    § Drs Gottlieb and Butnaru contributed equally to this work.
Published:December 02, 2021DOI:https://doi.org/10.1016/j.cjca.2021.11.016

      Abstract

      Background

      Strict isolation precautions limit formal echocardiography use in the setting of COVID-19 infection. Information on the importance of handheld focused ultrasound for cardiac evaluation in these patients is scarce. This study investigated the utility of a handheld echocardiography device in hospitalised patients with COVID-19 in diagnosing cardiac pathologies and predicting the composite end point of in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure.

      Methods

      From April 28 through July 27, 2020, consecutive patients diagnosed with COVID-19 underwent evaluation with the use of handheld ultrasound (Vscan Extend with Dual Probe; GE Healthcare) within 48 hours of admission. The patients were divided into 2 groups: “normal” and “abnormal” echocardiogram, as defined by biventricular systolic dysfunction/enlargement or moderate/severe valvular regurgitation/stenosis.

      Results

      Among 102 patients, 26 (25.5%) had abnormal echocardiograms. They were older with more comorbidities and more severe presenting symptoms compared with the group with normal echocardiograms. The prevalences of the composite outcome among low- and high-risk patients (oxygen saturation < 94%) were 3.1% and 27.1%, respectively. Multivariate logistic regression analysis revealed that an abnormal echocardiogram at presentation was independently associated with the composite end point (odds ratio 6.19, 95% confidence interval 1.50-25.57; P = 0.012).

      Conclusions

      An abnormal echocardiogram in COVID-19 infection settings is associated with a higher burden of medical comorbidities and independently predicts major adverse end points. Handheld focused echocardiography can be used as an important “rule-out” tool among high-risk patients with COVID-19 and should be integrated into their routine admission evaluation. However, its routine use among low-risk patients is not recommended.

      Résumé

      Contexte

      Les précautions d’isolement strictes limitent l’utilisation de l’échocardiographie formelle en présence de COVID-19. Les renseignements sur l’importance des appareils portatifs d’échographie focalisée pour l’évaluation cardiaque en pareil cas sont rares. La présente étude vise à examiner l’utilité d’un appareil d’échocardiographie portatif chez les patients hospitalisés atteints de COVID-19 pour le diagnostic de maladies cardiaques et pour la mesure du critère d’évaluation composé regroupant le décès en milieu hospitalier, la ventilation mécanique, le choc et l’insuffisance cardiaque en décompensation aiguë.

      Méthodologie

      Du 28 avril au 27 juillet 2020, des patients consécutifs ayant reçu un diagnostic de COVID-19 ont été évalués au moyen d’un échographe portatif (échographe Vscan Extend à double sonde de GE Healthcare) dans les 48 heures suivant leur admission. Les patients ont été répartis en deux groupes selon que l’échocardiogramme était « normal » ou « anormal », l’évaluation étant fondée sur la présence d’une dysfonction systolique ou d’une hypertrophie biventriculaire, ou d’une régurgitation ou d’une sténose valvulaires modérées ou graves.

      Résultats

      Parmi les 102 patients, 26 (25,5 %) présentaient un échocardiogramme anormal. Ils étaient plus âgés, avaient plus des comorbidités et présentaient des symptômes plus graves comparativement aux patients dont l’échocardiogramme était normal. La prévalence des manifestations formant le critère d’évaluation composé, chez les patients à risque faible et les patients à risque élevé (saturation en oxygène < 94 %), a été de 3,1 % et de 27,1 %, respectivement. Une analyse de régression logistique multivariée a révélé qu’un échocardiogramme anormal lors de l’admission était associé de façon indépendante au critère d’évaluation composé (rapport de cotes : 6,19, intervalle de confiance à 95 % : 1,50-25,57; p = 0,012).

      Conclusions

      Un échocardiogramme anormal dans un cas de COVID-19 est associé à un fardeau plus lourd sur le plan des maladies concomitantes, et permet de prédire de façon indépendante la survenue de manifestations graves. L’échocardiographie focalisée réalisée à l’aide d’un appareil portatif peut être un outil important pour exclure certains troubles chez les patients à risque élevé atteints de COVID-19 et devrait être intégrée dans l’évaluation systématique de ces patients au moment de l’admission. Toutefois, son utilisation systématique chez les patients à risque faible n’est pas recommandée.
      COVID-19 interacts with the cardiovascular system on multiple levels. It is well established that known cardiovascular disease or risk factors are associated with a significant increase in morbidity and mortality among patients with COVID-19. In addition, it has been demonstrated that elevation in cardiac biomarkers such as high-sensitivity cardiac troponin I (hs-cTnI) is correlated with a poor prognosis in COVID-19 patients.
      • Zhou F.
      • Ting Yu
      • Ronghui Du
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
      The association between COVID-19 and the cardiovascular system has led researchers to try to better identify predictors for severe disease and adverse outcomes. Possible predictors for disease severity might be cardiac systolic function, including left (LV) and right (RV) ventricular systolic function or valvular functional abnormalities as determined with the use of echocardiography. Routine echocardiographic evaluation of all patients admitted with COVID-19, however, is currently discouraged according to various guidelines and consensus papers owing to concerns of excessive workload in the setting of a pandemic,
      • European Society of Cardiology
      ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic.
      ,
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      ASE statement on protection of patients and echocardiography service providers during the 2019 novel coronavirus outbreak: endorsed by the American College of Cardiology.
      risk of infection of echocardiography professionals, and increased equipment contamination with long imaging times.
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      • et al.
      COVID-19 pandemic and cardiac imaging: EACVI recommendations on precautions, indications, prioritization, and protection for patients and healthcare personnel.
      Handheld ultrasound has been shown to be accurate when used by cardiologists for many aspects of cardiac evaluation. This includes evaluation of LV ejection fraction (LVEF), regional wall motion abnormalities, LV hypertrophy, inferior vena cava size, valvular pathology, and pericardial effusion.
      • Stoica R.
      • Heller E.N.
      • Bella J.N.
      Point-of-care screening for left ventricular hypertrophy and concentric geometry using hand-held cardiac ultrasound in hypertensive patients.
      ,
      • Khan H.A.
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      • et al.
      Can hospital rounds with pocket ultrasound by cardiologists reduce standard echocardiography?.
      As point-of-care ultrasound (POCUS) is increasingly being used, its application in cardiac systolic function assessment is likely to markedly increase.
      • Moore C.L.
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      Point-of-care ultrasonography.
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      • Goudie A.
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      • et al.
      Point of care ultrasound: a WFUMB position paper.
      LVEF, RV systolic function, and basic valvular function can be determined on admission by means of bedside echocardiography using the POCUS approach.
      • McKaigney C.J.
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      In addition, echocardiography with the use of handheld devices can be performed by noncardiologists, does not need a sonography technician, can be easily cleaned, and can be stored in COVID-19 units for ease of use without disruption to the clinical setting. Furthermore, some devices can be used for lung assessment as well, with a quick and > 90% accurate interpretation for common causes of acute respiratory failure.
      • Kiamanesh O.
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      • et al.
      Lung ultrasound for cardiologists in the time of COVID-19.
      The objective of the present study was to characterise the utility of handheld echocardiography in hospitalised patients with COVID-19 to predict end points based on identified cardiac abnormalities, including ventricular size and systolic function, and valvular pathologies.

      Methods

      Study setting

      This was a prospective study of real-time focused echocardiography and lung ultrasound performed using a handheld device. The study was conducted on consecutive patients with polymerase chain reaction–confirmed COVID-19 hospitalised in designated medical wards at a tertiary care medical center from April 28 through July 27, 2020. The study was approved by the hospital’s institutional review board.
      All echocardiographic clips were acquired by cardiologists or intensivists and were later interpreted by a fellowship-trained echocardiographer. Variables including demographics, past medical history, electrocardiography (ECG), imaging modalities, and laboratory results obtained from the medical record.

      Study end points

      The primary end point was defined as a composite end point of in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure (ADHF). Secondary end points included the composite end point, individual parameters of the composite end point, advanced ventilatory support (high-flow nasal cannula, noninvasive positive airway pressure support, and invasive ventilation), chronic ventilation, myocardial injury (defined as hs-cTnI > 3 times upper normal limit), venous thromboembolism, anti–COVID-19 drug use, sepsis, and length of hospital stay.

      Study protocol

      Patients with confirmed COVID-19 who were hospitalised in designated internal medicine departments were recruited into the study. Conscious patients consented verbally. Patients who were not able to give informed consent underwent echocardiography if it was clinically indicated. Patients that refused to participate in the study were excluded. Basic characteristics included age, sex, and known previous medical illness. Routine chest X-ray, ECG, and blood workup were performed for every patient on admission to the designated COVID-19 wards. The routine laboratory tests included complete blood count, renal function, electrolytes, hs-cTnI, d-dimer, coagulation function tests, and C-reactive protein (CRP). B-Type natriuretic peptide was measured according to the clinical judgment of the treating physician. The study physicians performing the ultrasound examination wore personal protective equipment including a full gown, N95 face mask, face shield, and at least 2 sets of gloves. Participants were evaluated by focused echocardiographic examination and lung ultrasound within 48 hours of their hospitalisation with the use of a handheld ultrasound machine (Vscan Extend with Dual Probe; General Electric, Northville, MI). The cardiac POCUS was conducted using the sector transducer from the apical, parasternal, and substernal views. Valves were evaluated visually using both 2-dimensional (2D) and color Doppler echocardiography. The acquired video clips were stored in the Digital Imaging and Communications in Medicine format and sent wirelessly to a picture archiving and use platform (McKesson Cardiology, version 14.0, Alpharetta, GA, USA) routinely used by the cardiology department. The echocardiogram clips were then interpreted by visual evaluation by an experienced echocardiographer (A.B.), blinded to the patient’s clinical course and presentation, for evaluation of LVEF and LV diameter, RV visual systolic function and RV diameter, severity of valvular dysfunction (the valves were visually assessed for functional abnormalities, ie, regurgitation or stenosis, with the use of both 2D and Doppler echocardiograms), pericardial effusion, and any additional significant echocardiographic findings. Offline measurements of LV end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE), and fractional area change were made. POCUS lung ultrasound was performed using the linear transducer and included a 10-location assessment (standard approach: 4 quadrants on each anterior hemithorax and 2 on each posterior hemithorax) for B-lines, subpleural consolidations/lung hepatisation, and pleural effusions. Each assessed variable was graded separately for each location according to the severity as 0 (normal), 1 (several lines or small consolidation/effusion), or 2 (coalescent B-lines or diffuse/widespread consolidation/effusion). The lung ultrasound assessment scoring was calculated as the sum of the entire graded variables (range of 0-20).

      Data management

      All data obtained in this study were entered into 2 Microsoft Excel spreadsheets. One file contained the case-identifying number, patient identifiers, and other pertinent variables. POCUS results were inserted into a second file by the patient’s identifying number. The 2 files were then matched.
      Study participants were divided into normal or abnormal echocardiograms according to POCUS results. Abnormal echocardiograms included those with LVEF < 50%, LV dilation, RV systolic dysfunction/dilation, and moderate/severe valvular dysfunction (functional regurgitation or stenosis).

      Statistical analyses

      The patients were divided into normal and abnormal echocardiograms, and analyses were performed accordingly. Descriptive statistics were used to analyse differences in baseline and clinical characteristics, echocardiography and lung ultrasound results, and end points, with the use of chi-square or Fisher exact test for categoric variables and t test or Mann-Whitney U test for continuous variables, as appropriate. Test selection was based on data distribution and normalcy.
      High-risk patients were defined as those with room-air oxygen saturation < 94%. The ability of the echocardiography results to identify patients with and without the composite outcome was then tested for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) among low- and high-risk patients.
      Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to test the univariate associations between abnormal echocardiogram and the composite end point and individual end points.
      Multivariate logistic regression analysis (OR and 95% CI) was calculated for the association between abnormal echocardiogram and the composite end point among the entire cohort and individually among high-risk patients, including pertinent baseline characteristics covariates (those with P values < 0.05). Statistical analyses were performed with the use of SPSS Statistics for Windows version 21 (SPSS, Chicago, IL, USA).

      Results

      A total of 102 hospitalised patients with COVID-19 were recruited into the study, including 76 (74.5%) with normal and 26 (25.5%) with abnormal echocardiograms (Table 1). Four patients refused to participate in the trial and were therefore excluded.
      Table 1Baseline and clinical characteristics
      VariableAll (n = 102)Normal echocardiogram (n = 76)Abnormal echocardiogram (n = 26)P value
      Baseline characteristics
      Age, years59.7 ± 18.457.0 ± 18.667.6 ± 15.50.010
      Male65 (63.7)48 (63.2)17 (65.4)0.838
      Body mass index, kg/m227.9 ± 6.227.6 ± 6.228.9 ± 6.20.378
      Smoking16 (15.7)8 (10.5)8 (30.8)0.014
      Diabetes mellitus33 (32.4)21 (27.6)12 (46.2)0.081
      Hypertension39 (38.2)23 (30.3)16 (61.5)0.005
      Hyperlipidemia32 (31.4)18 (23.7)14 (53.8)0.004
      IHD20 (19.6)9 (11.8)11 (42.3)0.001
      CVA5 (4.9)2 (2.6)3 (11.5)0.103
      Revascularisation17 (16.7)7 (9.2)10 (38.5)0.001
      Heart failure12 (11.8)3 (3.9)9 (34.6)< 0.001
      Valve replacement3 (2.9)0 (0.0)3 (11.5)0.015
      CIED3 (2.9)0 (0.0)3 (11.5)0.015
      Cognitive decline23 (22.5)14 (18.4)9 (34.6)0.088
      Debilitation26 (25.5)16 (21.1)10 (38.5)0.079
      Chronic lung disease9 (8.8)6 (7.9)3 (11.5)0.690
      Liver disease2 (2.0)2 (2.6)0 (0.0)1.000
      Previous VTE4 (3.9)2 (2.6)2 (7.7)0.268
      Malignancy2 (2.0)1 (1.3)1 (3.8)0.447
      Immunosuppression4 (3.9)3 (3.9)1 (3.8)1.000
      Hypothyroidism13 (12.7)8 (10.5)5 (19.2)0.251
      Chronic medications
      ACE-I/ARB24 (23.5)14 (18.4)10 (38.5)0.038
      β-Blockers29 (28.4)15 (19.7)14 (53.8)0.001
      CCB12 (11.8)9 (11.8)3 (11.5)1.000
      Antiplatelets26 (25.5)12 (15.8)14 (53.8)< 0.001
      Oral anticoagulation13 (12.7)8 (10.5)5 (19.2)0.251
      Diuretics11 (10.8)4 (5.3)7 (26.9)0.005
      Inhalations7 (6.9)5 (6.6)2 (7.7)1.000
      SGLT2 inhibitors7 (6.9)5 (6.6)2 (7.7)1.000
      Statins33 (32.4)17 (22.4)16 (61.5)< 0.001
      COVID-19 presentation
      Chest pain28 (27.5)22 (28.9)6 (23.1)0.563
      Shortness of breath54 (52.9)37 (48.7)17 (65.4)0.141
      HR, beats/min88.8 ± 22.388.1 ± 19.390.7 ± 30.00.626
      SBP, mm Hg124.3 ± 20.9123.4 ± 19.9126.8 ± 23.70.461
      DBP, mm Hg74.1 ± 12.073.6 ± 11.275.6 ± 14.30.375
      SpO2, %87.4 ± 11.487.3 ± 11.987.8 ± 10.30.752
      In-hospital course
      Sinus bradycardia2 (2.0)2 (2.7)0 (0.0)1.000
      ECG changes0.040
       Normal74 (72.5)59 (77.6)15 (57.7)
       Nonspecific changes19 (18.6)12 (15.8)7 (26.9)
       TWI/ST-segment depression6 (5.9)4 (5.3)2 (7.7)
       ST-segment elevation2 (2.0)0 (0.0)2 (7.7)
      Chest X-ray infiltrates75 (73.5)51 (67.1)24 (92.3)0.012
      AF/AFL11 (10.8)7 (9.2)4 (15.4)0.130
      Laboratory results
      WBC (p), 103/μL10.4 ± 5.79.6 ± 5.012.8 ± 6.70.013
      ANC/ALC (a)5.9 (3.0-10.6)5.4 (2.6-8.9)9.0 (4.4-13.4)0.032
      Hemoglobin (a), g/dL13.0 ± 2.313.1 ± 2.112.6 ± 2.70.240
      Platelets (a), 103/μL200.6 ± 73.6203.0 ± 73.3193.2 ± 75.30.802
      Creatinine (a), mg/dL1.0 ± 0.70.9 ± 0.41.4 ± 1.10.002
      K (a), mmol/L4.0 ± 0.63.9 ± 0.54.1 ± 0.70.168
      Albumin (t), g/dL3.0 ± 0.83.1 ± 0.82.6 ± 0.70.044
      hs-cTnI (p), ng/L7.0 (5.0-40.8)5.5 (5.0-22.0)37 (6.5-541.5)0.001
      BNP (a), pg/mL76.5 (22.5-229.5)59.8 (15.0-200.8)224.5 (94.5-753.5)0.065
      CRP (p), mg/L13.0 ± 11.811.2 ± 11.618.2 ± 10.90.003
      d-dimer (p), ng/mL925 (522-1188)803 (392-1362)1178 (878-2707)0.014
      Fibrinogen (a), mg/dL594.9 ± 186.5572.9 ± 187.8660.1 ± 169.30.015
      aPTT (p), seconds35.0 ± 9.733.9 ± 9.738.1 ± 9.20.009
      Values are presented as mean ± SD, n (%), or median (interquartile range).
      a, admission; ACE-I, angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; AFL, atrial flutter; ALC, absolute lymphocytes count; ANC, absolute neutrophils count; aPTT, activated partial thromboplastin time; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; CCB, calcium channel blocker; CIED, cardiovascular implantable electronic device; CRP, C-reactive protein; CVA, cerebrovascular accident; DBP, diastolic blood pressure; ECG, electrocardiography; HR, heart rate; hs-cTnI, high sensitive cardiac troponin I; IHD, ischemic heart disease; IQR, interquartile range; K, potassium; p, peak; SBP, systolic blood pressure; SGLT2, sodium-glucose transport protein 2; SpO2, oxygen saturation; t, trough; TWI, T-wave inversion; VTE, venous thromboembolism; WBC, white blood cells.

      Baseline and medical characteristics

      As presented in Table 1, the mean age of the total cohort was 59.7 ± 18.4 years, and 63.7% were male. Patients with an abnormal echocardiogram were older and more likely to suffer from comorbidities including smoking, hypertension, hyperlipidemia, ischemic heart disease, past revascularisation, and heart failure compared with patients with a normal echocardiogram. They had a higher proportion of past valve replacement and cardiac implantable electronic devices. Moreover, they were treated more often with chronic heart failure evidence-based medications, antiplatelets, diuretics, and statins.

      Presentation characteristics and laboratory results

      As presented in Table 1, the 2 groups did not differ in their presenting complaints or vital signs. Patients with abnormal echocardiograms had a higher rate of pathologic ECG (including nonspecific and ST-segment changes or T-wave inversion) and chest X-ray infiltrates, compared with those with normal echocardiograms. Laboratory results of creatinine, hs-cTnI, fibrinogen, activated partial thromboplastin time, white blood cell count, neutrophil/lymphocyte count ratio, CRP, and d-dimer were higher in the abnormal than in the normal echocardiogram group, whereas albumin was lower.

      Echocardiography and lung ultrasound results

      Echocardiography and lung ultrasound results are presented in Table 2. Compared with patients with a normal echocardiogram, those with an abnormal echocardiogram had a lower LVEF (49.2 ± 8.2% vs 57.2 ± 4.1%; P < 0.001), higher LVEDD (4.8 ± 0.6 cm vs 4.5 ± 0.5 cm; P = 0.016), and higher proportions of LVEF < 50%, RV systolic dysfunction and dilation, pericardial effusion, and significant valvulopathy (including significant mitral and tricuspid regurgitation and aortic stenosis). Comparing lung scores between patients with a normal echocardiogram and those with an abnormal echocardiogram yielded no association (2.9 ± 2.4 vs 3.7 ± 2.5; P = 0.119).
      Table 2Echocardiography results, measurements, and lung ultrasound score for patients with and without in-hospital advanced ventilatory support
      ParameterAll (n = 102)Normal echocardiogram (n = 76)Abnormal echocardiogram
      Abnormal echocardiogram was defined as left or right ventricular dysfunction or enlargement, or moderate/severe valvular regurgitation/stenosis echocardiographic study.
      (n = 26)
      P value
      P value for the difference between normal and abnormal echocardiograms.
      No advanced ventilatory support (n = 76)Advanced ventilatory support (n = 26)P value
      P value for the difference between advanced ventilatory support and no support.
      LVEF, %53.4 ± 6.857.2 ± 4.149.2 ± 8.2< 0.00155.8 ± 6.353.4 ± 6.60.096
      LVEF < 50%16 (15.7)0 (0.0)16 (61.5)< 0.0019 (11.8)7 (26.9)0.068
      LVEDD, cm4.6 ± 0.54.5 ± 0.54.8 ± 0.60.0164.6 ± 0.64.6 ± 0.50.692
      RV dysfunction8 (7.8)0 (0.0)8 (30.8)< 0.0015 (6.6)3 (11.5)0.425
      RV dilation7 (6.7)0 (0.0)7 (26.9)< 0.0015 (6.6)2 (7.7)1.000
      Ventricular abnormality24 (23.5)0 (0.0)24 (92.3)< 0.00114 (18.4)10 (38.5)0.034
      TAPSE, cm1.9 ± 0.32.0 ± 0.31.8 ± 0.20.1592.0 ± 0.31.8 ± 0.20.045
      FAC, %35.2 ± 6.535.6 ± 6.034.1 ± 7.70.51834.9 ± 6.536.4 ± 6.70.563
      Significant MR7 (6.9)0 (0.0)7 (26.9)< 0.0014 (5.3)3 (11.5)0.365
      Significant TR6 (5.9)0 (0.0)6 (23.1)< 0.0013 (3.9)3 (11.5)0.167
      Significant AS6 (5.9)0 (0.0)6 (23.1)< 0.0014 (5.3)2 (7.7)0.636
      Significant valvulopathy9 (8.8)0 (0.0)9 (34.6)< 0.0015 (6.6)4 (15.4)0.225
      Pericardial effusion6 (5.9)0 (0.0)6 (23.1)< 0.0013 (3.9)3 (11.5)0.171
      Lung score3.1 ± 2.42.9 ± 2.43.7 ± 2.50.1192.7 ± 2.34.5 ± 2.40.001
      Values are presented as mean ± SD or n (%).
      AS, aortic stenosis; FAC, fractional area change; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; RV, right ventricular; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation.
      Abnormal echocardiogram was defined as left or right ventricular dysfunction or enlargement, or moderate/severe valvular regurgitation/stenosis echocardiographic study.
      P value for the difference between normal and abnormal echocardiograms.
      P value for the difference between advanced ventilatory support and no support.
      Four patients underwent an official echocardiography after the study examination during the index hospitalisation, which confirmed the findings of the focused echocardiogram.

      Results among patients with and without advanced ventilatory support

      Echocardiogram results and measurements among patients with and without advanced ventilatory support are presented in Table 2. Compared with patients with no advanced ventilatory support, patients with such support had a higher proportion of ventricular abnormalities (38.5% vs 18.4%; P = 0.034), a lower TAPSE (1.8 ± 0.2 cm vs 2.0 ± 0.3 cm; P = 0.045) and a higher lung score (4.5 ± 2.4 vs 2.7 ± 2.3; P = 0.001). The groups did not differ in other assessed or measured POCUS parameters.

      Sensitivity and specificity among low- and high-risk patients

      Among the 102 patients included in the study, only 32 were defined as low risk (with room-air oxygen saturation ≥ 94%), including 6 patients with abnormal echocardiograms, of which only 1 patient had the composite outcome. The sensitivity of focused echocardiography for the composite outcome among low-risk patients was 100% and the specificity 83.9% with PPV 16.7% and NPV 100%.
      Among the 70 patients defined as high risk (with room-air oxygen saturation < 94%), the sensitivity of focused echocardiography for the composite outcome was 57.9% and the specificity 82.4% with PPV 55.0% and NPV 84.0%.

      Association between abnormal echocardiogram and study end points

      The associations between an abnormal echocardiogram and the end points are presented in Table 3 and Figure 1. An abnormal echocardiogram was associated with the end points of the need for advanced ventilatory support, ADHF, myocardial injury, acute kidney injury, death, and the composite end point (in-hospital death, mechanical ventilation, shock, and ADHF; unadjusted OR 7.29, 95% CI 2.44-20.00).
      Table 3The association between abnormal echocardiogram and serious adverse events (end points)
      VariableAll (n = 102)Normal echocardiography (n = 76)Abnormal echocardiography (n = 26)P valueUnadjusted OR (95% CI)
      Composite outcome
      Composite outcome included in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure.
      20 (19.6)8 (10.5)12 (46.2)< 0.0017.29 (2.44-20.00)
       In-hospital death6 (5.9)2 (2.6)4 (15.4)0.0336.82 (1.2-39.7)
       Mechanical ventilation12 (11.8)7 (9.2)5 (19.2)0.1642.38 (0.68-8.29)
       Shock7 (6.9)4 (5.3)3 (11.5)0.2492.35 (0.5-11.3)
       ADHF6 (5.9)0 (0.0)6 (23.1)0.00522.8 (2.6-200.4)
      Advanced ventilatory support26 (25.5)15 (19.7)11 (42.3)0.0214.83 (1.5-15.3)
      Myocardial injury14 (13.7)6 (7.9)8 (30.8)0.0035.19 (1.6-19.9)
      Chronic ventilation9 (8.8)6 (7.9)3 (11.5)0.4141.52 (0.4-6.6)
      Venous thromboembolism3 (2.9)2 (2.6)1 (3.8)1.0001.48 (0.1-17.0)
      Anti–COVID-19 drugs40 (39.2)27 (35.5)13 (50.0)0.1921.82 (0.7-4.7)
      Sepsis11 (10.8)6 (7.9)5 (19.2)0.1082.78 (0.8-10.0)
      Acute kidney injury20 (19.6)9 (11.8)11 (42.3)0.0015.46 (1.9-15.5)
      New renal replacement therapy3 (2.9)0 (0.0)3 (11.5)0.0529.9 (0.98-99.9)
      LOS, days8.1 (3.0-16.3)7 (2.8-14.1)10.4 (6.8-29.3)0.2025.07 (−2.75-12.89)
      Values are presented as n (%) or median (interquartile range).
      ADHF, acute decompensated heart failure; CI, confidence interval; LOS, length of stay; OR, odds ratio.
      Composite outcome included in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure.
      Figure thumbnail gr1
      Figure 1Significant associations (odds ratio [OR] and 95% confidence interval [CI]) between abnormal echocardiogram and serious adverse events (end points). ∗The primary end point was defined as a composite end point of in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure. Numeric results of OR and 95% CI and are detailed in . ADHF, acute decompensated heart failure; Adv., advanced; AKI, acute kidney injury.
      Multivariate analysis adjusting for age, heart failure, ischemic heart disease, smoking, hypertension, hyperlipidemia, previous revascularisation, cardiovascular implantable electronic device (CIED) implantation, or valve replacement revealed that among the entire cohort, an abnormal echocardiogram was independently associated with a higher probability for the composite end point (OR 6.19, 95% CI 1.50-25.57; P = 0.012).
      Multivariate analysis adjusting for age, heart failure, hypertension, hyperlipidemia, smoking, and CIED implantation revealed that among high-risk patients, an abnormal echocardiogram was independently associated with a higher probability for the composite end point (OR 5.47, 95% CI 1.29-23.30; P = 0.022).

      Association between lung score and study end points

      The lung score was associated with the end points of the need for advanced ventilatory support, anti–COVID-19 medication use, myocardial injury, hospital length of stay, mechanical ventilation, ADHF, in-hospital death, and the composite end point (unadjusted OR 1.44, 95% CI 1.18-1.77).
      Multivariate analysis adjusting for the above pertinent variables revealed that the continuous lung score was independently associated with a higher probability for the composite end point (OR 1.56, 95% CI 1.12-2.03; P = 0.001).

      Discussion

      This study is, to the best of our knowledge, the first to investigate the utility of handheld echocardiography in hospitalised patients with COVID-19 to predict end points based on identified cardiac abnormalities. Hospitalised patients with COVID-19 and an abnormal echocardiogram presented with a higher proportion of comorbidities and worse baseline functioning. Abnormal ventricular function/size or significant valvular pathology identified with the use of handheld ultrasound were associated with worse end points and were independently predictive of the composite end point of death, mechanical ventilation, shock, and ADHF. Also, the lung score with the use of a handheld ultrasound was associated with worse end points and was independently predictive of the composite end point. Among low-risk patients (with room-air oxygen saturation ≥ 94%) the prevalence of the composite end point was very low (3.1%) and focused echocardiography had a positive predictive value of only 14.3% in this group of patients.
      COVID-19 is known to manifest a wide spectrum of cardiac pathologies and the use of echocardiography in these patients has an important role in the settings of myocarditis, acute coronary syndrome, cardiomyopathy, pericardial effusion, arrhythmia, and shock. Therefore, a timely echocardiogram is integral to the clinical evaluation and management of patients with COVID-19. The burden of the pandemic on health care systems necessitates achieving an appropriate balance between the relative necessity of the examination and the duty of sonographers, nurses, advanced practice providers, and physicians to provide high-quality imaging while limiting viral spread, reducing staff exposure, and protecting patients. In these settings, traditional criteria for echocardiography use seem too extensive and clinicians are required to prioritise the need for this valuable resource. The handheld devices have smaller nonsterile exposed areas compared with standard machines and can be easily decontaminated with disinfectant wipes, and their size allows for them to be entirely enclosed by a sterile covering to limit iatrogenic virus transmission.
      • Jenkins S.
      • Garg P.
      Prime time for handheld echocardiography in COVID-19 pandemic.
      ,
      • Gibson L.E.
      • Bittner E.A.
      • Chang M.G.
      Handheld ultrasound devices: an emerging technology to reduce viral spread during the Covid-19 pandemic.
      The findings of the present study support the acquisition of a cardiac assessment sonographic tool that can be dedicated to the COVID-19 departments and can be operated more conveniently in accordance with recommended precautions.
      An abnormal echocardiogram was observed in 25.5% of the study population. Other studies using standard cart-based machines or laptops and conducted on hospitalised patients with COVID-19 have found a relatively high rate of sonography-based cardiac abnormalities, ranging up to 68%, with RV systolic dysfunction being the most predominant finding (10%-52.8%).
      • Szekely Y.
      • Lichter Y.
      • Taieb P.
      • et al.
      Spectrum of cardiac manifestations in COVID-19: a systematic echocardiographic study.
      • Li Y.
      • Li H.
      • Li M.
      • Zhang L.
      • Xie M.
      The prevalence, risk factors and outcome of cardiac dysfunction in hospitalized patients with COVID-19.
      • Jain S.S.
      • Liu Q.
      • Raikhelkar J.
      • et al.
      Indications for and findings on transthoracic echocardiography in COVID-19.
      • Moody W.E.
      • Mahmoud-Elsayed H.M.
      • Senior J.
      • et al.
      Impact of right ventricular dysfunction on mortality in patients hospitalized with COVID-19, according to race.
      • van den Heuvel F.M.
      • Vos J.L.
      • Koop Y.
      • et al.
      Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19.
      • Mahmoud-Elsayed H.M.
      • Moody W.E.
      • Bradlow W.M.
      • et al.
      Echocardiographic findings in patients with COVID-19 pneumonia.
      • Dweck M.R.
      • Bularga A.
      • Hahn R.T.
      • et al.
      Global evaluation of echocardiography in patients with COVID-19.
      This discrepancy may be explained by selection bias (patients with advanced illness), differing timelines between echocardiography and disease onset, lack of Doppler usage, partial RV visualisation, and discrepancies in the definition of an abnormal echocardiogram. Another important difference is the use of high-end devices or detailed full echocardiographic examinations in most of the studies. Because none of the studies used handheld ultrasound, their examination may be more meticulous but less practical in the COVID-19 clinical setting.
      An example of studies focusing on patients with advanced illness is one in which an echocardiogram was performed only after approval by 3 physicians and on patients with elevated high-sensitivity troponin or a clinical need for the examination.
      • Mahmoud-Elsayed H.M.
      • Moody W.E.
      • Bradlow W.M.
      • et al.
      Echocardiographic findings in patients with COVID-19 pneumonia.
      In that study, 82% of the patients required mechanical ventilation and 58% required vasopressor support. A correlation between disease severity and the prevalence of an abnormal echocardiogram can be found in a cross-sectional study comparing patients with nonsevere COVID-19 and those with severe disease, demonstrating larger biventricular diameters alongside lower LVEF and RV fractional area change in those with severe disease.
      • Barman H.A.
      • Atici A.
      • Tekin E.A.
      • et al.
      Echocardiographic features of patients with COVID-19 infection: a cross-sectional study.
      An association between mortality and cardiac abnormality on the echocardiogram was also found by Karagodin et al., who demonstrated an association between both LV and RV strain and mortality.
      • Karagodin I.
      • Singulane C.C.
      • Woodward G.M.
      • et al.
      WASE-COVID Investigators
      Echocardiographic correlates of in-hospital death in patients with acute COVID-19 infection: the World Alliance Societies of Echocardiography (WASE-COVID) study.
      However, the routine use of strain for ventricular assessment is limited for patients hospitalised in COVID-19–designated departments. Also, unlike in our study, their cohort included a very high in-hospital mortality rate of 21.6%, which may reflect selection bias of patients with more severe COVID-19.

      Study limitations

      This was a prospective, single-centre, observational study and not a randomised trial, and as such is subjected to associated confounding factors. However, after constructing a multivariate analysis, the independent predictive value remained substantial. Also, data regarding previous echocardiographic examinations are lacking and not included in the analysis. Lack of pulsed- and continuous-wave Doppler usage and simultaneous electrocardiography limited the evaluation of valvular pathologies, hemodynamics, and echocardiographic images, which may have led to an underestimation of cardiac pathologies. Nonetheless, the study provides data in real-world settings that are relevant to the day-to-day limited clinical use of POCUS echocardiography in COVID-19 wards. A prospective POCUS study with noncardiologists vs cardiologists and low-risk vs high-risk patients would assist in clarifying the limitations of this study.

      Conclusion

      Abnormal echocardiographic results in hospitalised patients with COVID-19, when performed by a cardiologist or intensivist and interpreted by a fellowship-trained echocardiographer in a tertiary care setting, are associated with a higher burden of comorbidities and independently predict major adverse end points. Hand-held POCUS of hospitalised patients with COVID-19 can be utilized as an important “rule-out” tool among high-risk patients (with room-air oxygen saturation < 94%) and should be integrated as part of their routine admission evaluation. The routine use of focused echocardiography among low-risk patients is not recommended for prognostication or as a screening tool.

      Acknowledgements

      The authors thank GE Healthcare for the temporary supply of a Vscan Extend ultrasound device for research purposes.

      Funding Sources

      This study was funded by Shaare Zedek Scientific (fund no. 18004712), Shaare Zedek Medical Center’s technology transfer company.

      Disclosures

      The authors have no conflicts of interest to disclose.

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