Successfully reported this slideshow.
Your SlideShare is downloading. ×

Pocus in acute ischemic stroke.docx

More Related Content

Similar to Pocus in acute ischemic stroke.docx

Pocus in acute ischemic stroke.docx

  1. 1. Original Contribution SCREENING OF EMBOLIC SOURCES BY POINT-OF-CARE ULTRASOUND IN THE ACUTE PHASE OF ISCHEMIC STROKE TAGGEDPJESUS JUEGA,*,y JORGE PAGOLA,*,y TERESA GONZALEZ-ALUJAS,z DAVID RODRIGUEZ-LUNA,*,y MARTA RUBIERA,* NOELIA RODRIGUEZ-VILLATORO,* ALVARO GARCIA-TORNEL,* MANUEL REQUENA,* MATIAS DECK,* LAIA SERO,* SANDRA BONED,*,y MARC RIBO,*,y MARIAN MUCHADA,* MARTA OLIVE,* ESTELA SANJUAN,* JAIME CARVAJAL,x JOSE ALVAREZ-SABIN,*,y ARTURO EVANGELISTA,z and CARLOS MOLINA*,y TAGGEDEND * Stroke Unit, Department of Neurology, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Barcelona, Spain; y Department de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain; z Laboratory of Echocardiography, Department of Cardiology Vall d’Hebron University Hospital, Barcelona, Spain; and x Neurology Department Hospital Regional de Coyhaique, Aysen, Chile (Received 15 October 2019; revised 7 May 2020; in final from 8 May 2020) Abstract—Our objective was to evaluate hand-held echocardiography as point of care ultrasound scanning (POCUS) to detect sources of embolism in the acute phase of stroke. Prospective, unicentric observational cohort study of non-lacunar ischemic stroke patients evaluated by V Scan device. The main sources of embolism (MSEs) were classified into embolic valvulopathies and severe ventricular dysfunction. We looked for atrial fibrillation (AF) predictors in strokes of undetermined etiology. MSEs were detected in 19.23% (25/130). Large vessel occlusion (LVO) (odds ratio [OR]: 4.24, 95% confidence interval [CI]: 1.01À17.85) and chronic heart failure (OR: 13.25, 95% CI: 3.54À49.50) were independent predictors of MSEs. LVO (OR: 6.54, 95% CI: 1.62À26.27) and left atrial area 20 cm2 (OR: 7.01, 95% CI: 1.75À28.09) independently predicted AF. Patients with LVO and chronic heart disease may benefit from hand-held echocardiography as part of POCUS in the acute phase of ischemic stroke. Left atrial area measured was an independent predictor of AF in strokes of undetermined etiology. (E-mail: © 2020 World Federation for Ultrasound in Medicine Biology. All rights reserved. Key Words: Acute stroke, Echocardiography, Intracranial embolism, Diagnosis, Ultrasound, Secondary prevention. INTRODUCTION Cardioembolic strokes represent 20% of stroke cases. The main sources of embolism (MSEs) are atrial fibrillation (AF), severe ventricular dysfunction, severe rheumatic mitral stenosis and prosthetic valvular disease (Pepi et al. 2010; Pagola et al. 2017; Ferreira et al. 2018; Yang et al. 2018). Cardioembolic strokes were associated with higher morbid- ity than other subtypes in some series; 27% early in-hospital mortality and 10% early recurrence (Arboix and Alio 2012). Echocardiography has potential therapeutic implica- tions in patients with ischemic stroke in sinus rhythm (Abreu et al. 2005; Saric et al. 2016). Additionally, an enlarged left atrium assessed with transthoracic echocardiography (TTE) is an independent predictor of AF after stroke (Jordan et al. 2019). Point-of-care ultrasound scanning (POCUS) per- formed by trained operators could be a useful tool in assess- ing heart disease in screening programs (Evangelista et al. 2016). Previous studies have indicated that prior trained neu- rologists can perform focused echocardiography to assess the main sources of stroke embolism (Pagola et al. 2015). Indeed, a consensus document on recommendations for per- forming focused cardiac ultrasound for non-cardiologists has recently been published (Perez de Isla et al. 2018). The aim of this study was to assess which patients benefit from hand- held echocardiography (HHE) as POCUS screening in the acute phase of stroke. METHODS Study setting and population We conducted a prospective, unicentric study of non-lacunar ischemic stroke patients admitted to the Address correspondence to: Jesus Juega, Passeig de la Vall d’Hebron, 119-129, 08035 Barcelona, Spain. E-mail: 1 ARTICLE IN PRESS Ultrasound in Med. Biol., Vol. 00, No. 00, pp. 1À8, 2020 Copyright © 2020 World Federation for Ultrasound in Medicine Biology. All rights reserved. Printed in the USA. All rights reserved. 0301-5629/$ - see front matter
  2. 2. Stroke Unit or Emergency Department at our center from January 2016 to January 2018. All patients were evalu- ated within the first 24 h from stroke onset. We excluded patients with a poor echocardiographic window, clinical instability or any condition that did not allow HHE examination. We collected demographic data, vascular risk factors, stroke severity and cerebral infarct charac- teristics. Certified neurologists graded stroke severity according to the National Institutes of Health Stroke Scale (NIHSS). Strokes scored 8 points were classi- fied as moderate, and those scored 9 points as severe (Muchada et al. 2014). Reperfusion treatment (intravenous fibrinolysis) and/ or endovascular treat- ment were decided based on consensus guidelines for the treatment of acute stroke (Powers et al. 2018). HHE is TTE performed by a trained neurologist as a focused echo on stroke sources according to POCUS recommendations adapted to the acute phase of the stroke to avoid treatment delay. Therefore, HHE studies were performed in the Emergency Department, Stroke Unit, computed tomography (CT) suite or angiography suite after acute neuroimaging or stroke reperfusion therapy was concluded (Ribo et al. 2017). In the acute phase, all patients with non-lacunar stroke underwent CT scan to rule out intracranial hemorrhage. Extracranial and intracranial circulation was assessed by CT angiography or arteri- ography to detect branch or mainstem occlusion of intracranial arteries probably of embolic origin and known as large vessel occlusion (LVO) (Leslie- Mazwi et al. 2018). Patients were classified as hav- ing cardioembolic (CE) strokes or large arterial ath- erosclerosis (LAA) strokes if significant symptomatic (50%) stenosis or occlusion, presumably caused by atherosclerosis or stroke of undetermined etiology based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of stroke (Adams et al. 1993) was detected. Strokes of undetermined etiology were cases without known CE cause of stroke or LAA by diagnostic workup. We evaluated predictors of MSE and AF detection with HHE in patients with undetermined etiology. Patients in whom MSEs were not detected were monitored with a cardiac telemetry monitoring device to detect hid- den, undiagnosed AF (Fig. 1). Study design The study was approved by the Committee of Ethics in Medical Research of the Hospital Project Research Area General (PR (AG) 146/2016) and carried out in line with the second Declaration of Helsinki. Writ- ten informed consent was obtained from all participants or their relatives. Echocardiographic protocol The HHE protocol was carried out using an ultra- portable device (Vscan, GE Healthcare, Chicago, IL, USA) that acquires 2-D echo miniaturized images (size: 135 £ 73 £ 28 mm, weight: 390 g); it is a battery-oper- ated (total scan time of 1 h) device with a broadband width (1.7À3.8 MHz) phased array probe (120 £ 33 £ 26 mm). This system can store digital still frames or image loops, uses a color-coded overlay for real-time blood flow imaging and allows distance measurements using integrated electronic calipers, but has neither spec- tral nor tissue Doppler capability. We examined all four transthoracic windows after regular echocardiography examination routine. Each HHE study was conducted by the same stroke neurologist, who had been trained for 1 y in focused echocardiography and had performed more than 350 echocardiographic studies under the appropri- ate supervision of an expert echocardiographer in a high- volume laboratory (Popescu et al. 2009). This physician was blind to patient medical records. HHE was used to assess cardiac structure and function as follows. To eval- uate cardiac function, first we performed a qualitative assessment of left ventricular (LV) systolic function in the apical four-and two-chamber views (Cardim et al. 2019)), based on visual estimation of LV ejection frac- tion (LVEF). Second, we classified LVEF into the fol- lowing categories: normal (LVEF 50%), moderately reduced (LVEF 30%À50%) and severely reduced (LVEF 30%) (akinesia) (Amiel et al. 2012). Similarly, valvular heart evaluation focuses on valve morphology (including rheumatic disease). Mitral stenosis was suspected on the basis of color aliasing in combination with the reduction in mobility of the mitral valve. Presence of turbulent flow was assessed qualita- tively on a 2-D basis and on color Doppler images; quan- titative assessment of valvular heart disease is impossible because of the absence of spectral Doppler (Cardim et al. 2019). Left atrial (LA) diameter was obtained in the parasternal long-axis view, and LA area, in the four-chamber apical window on echocardio- graphic consensus (Lang et al. 2015). All patients underwent TTE examination within the first 72 h of stroke as standard-of-care protocol in our center. We compared HHE with TTE (gold standard test) to evaluate the ability to detect MSEs, which were defined as embolic valvulopathies (EVs) and severe ven- tricular dysfunction (SVD). In detail, EVs included masses suggestive of endocarditis or fibroelastoma, mitral or aortic mechanical prosthesis and rheumatic mitral valve stenosis. SVD was defined as ventricular akinesia or global hypokinesia with severely depressed LVEF and intracardiac masses or floating thrombi. We considered transient embolic sources (as mobile throm- bus, takotsubo disease, or cardiomyopathies that ARTICLE IN PRESS 2 Ultrasound in Medicine Biology Volume 00, Number 00, 2020
  3. 3. disappeared or improved after days in control TTE) (Bersano et al. 2014). Emergent transesophageal echo- cardiography (TEE) was ordered only for cases with valvular prostheses or with suspected endocarditis (Habib et al. 2010; Sala-Padro et al. 2017). In addition, ambulatory TEE was performed in those suspected of Fig. 1. Flowchart of the study. The study included eligible patients with non-lacunar symptoms and brain computed tomography imaging that excluded brain hemorrhage or tumor. On the basis of medical records and acute neuroimaging, patients were classified as known source of stroke, such as cardioembolic (CE) strokes in patients with known atrial fibrilla- tion (AF) or prosthetic valves, and large arterial atherosclerosis (LAA) strokes. Strokes of unknown etiology with good con- cordance between hand-held echocardiography (HHE) and transthoracic echocardiography (TTE) studies were divided into patients with large vessel occlusion (LVO) and patients without LVO. There were two main groups of interest: strokes related to diagnosis of main sources of embolism (MSEs), and strokes in patients with no MSEs in HHE studies. Patients without MSEs were considered to have strokes of undetermined source and were classified as an enlarged left atrium (LA) if the LA area was 20 cm2 on HHE studies and as AF until 1 y of follow-up was recorded in each group. ARTICLE IN PRESS Hand-held echocardiography as POCUS in acute ischemic stroke J. JUEGA et al. 3
  4. 4. having complex aortic atheromatosis or on detection of patent foramen ovale. Atrial fibrillation detection Atrial fibrillation was defined as irregularly irregu- lar RÀR intervals without P-wave signal. Heart rhythm analyses were carried out with electrocardiograms, in- hospital cardiac telemetry monitoring with automatic software and medical record review up to 1 y from hos- pital discharge. We evaluated LA diameter and LA area measured by HHE as surrogates of AF detection until 1 y of follow-up in patients with sinus rhythm and undeter- mined stroke (Table 1). Diagnostic yield Diagnostic yield was defined as the ability of HHE to detect at least one MSE confirmed by TTE. We described the main differences between patients with and without MSE detection according to demographic characteristics, previous diseases and stroke characteris- tics (Table 2). The correlation with the final detection of AF was measured by risk of AF detection in patients with enlarged LA area measured by HHE. The aim was to detect unknown CE sources of stroke: MSE diagnosis or AF detection according to HHE predictors. Data analysis We employed the SPSS 17 statistical package to analyze the data. The results of HHE studies were coded in dichotomous variables according to the presence or absence of the event, and the comparison was made by x2 or Fisher’s exact test when required. A p value 0.05 was considered to indicate statistical significance. To test the validity of HHE, we calculated its sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). In addition, the k concordance coefficient was calculated. Multivariate logistic regres- sion analysis including significant variables in univariate analysis was employed to predict MSE and AF detection. The predictive accuracy of HHE covariates related to AF detection was evaluated using receiver operating charac- teristic (ROC) curve analysis. RESULTS Of 155 eligible patients, we included 130 patients with HHE and TTE evaluation. Those patients who did not have a good thoracic window, were lost to follow-up and did not have an ischemic stroke were excluded. Fifty-seven percent of HHE examinations were per- formed within the first 6 h from stroke onset (75/130). The average duration of the HHE examination was 9.2 min (standard deviation 5.3). Twenty-four patients were classified as having stroke secondary to a known cause (LAA or CE strokes) based on medical records and acute neuroimaging, whereas 106 patients were clas- sified as having a stroke of unknown etiology (Fig. 1). According to the validation of HHE, 98.46% of patients (128/130) were properly diagnosed by HHE, and 1.54% (2/130) were misdiagnosed: 1 patient with papillary fibroelastoma and one false diagnosis of SVD in a patient with mild dysfunction according to TTE. The percentage of MSE detection was 19.23% (25/130). With respect to MSE type, 7 patients had EV, 17 patients had SVD and 1 patient had both EV and SVD, which were analyzed separately. TEE was superior for Table 1. Baseline characteristics of strokes with no MSE on hand-held echocardiography and diagnosis of AF on follow-up (N = 130)* No MSEy (n = 87) AF (n = 18) No AF (n = 69) p Value Age, y [IQR] 76 [63À82] 79 [77À83] 72 [60À80] 0.007 Sex (female) 52.9% (46)y 44.4% (8) 55.1% (38) 0.421 Hypertension 75% (63) 83.3% (15) 72.7 (48) 0.357 Diabetes mellitus 22.4% (19) 16.7% (3) 23.9% (16) 0.514 Dyslipidemia 54.1% (46) 66.7% (12) 50.7% (34) 0.229 Former or past smoker 25.9% (22) 16.7% (3) 28.4% (19) 0.315 Coronary artery disease 12.6% (11) 5.6% (1) 14.5% (10) 0.310 Chronic heart failure 7.1% (6) 3% (17.6) 4.5% (3) 0.060 Previous stroke 18.8% (16) 4.7% (4) 14.1% (12) 0.678 Basal NIHSS, median [IQR] 7.0 [3.7À14.0] 11.0 [7.0À17.5] 6 [2.5À11.0] 0.016 Mild strokes 56.3% (49) 44.4% ( 8) 59.4% (41) 0.254 Moderate to severe stroke 43.7% (38) 55.6% (10) 40.6% (28) 0.254 Large vessel occlusion 48.3% (42) 83.3% (15) 39.1% (27) 0.001 Intravenous alteplase 43.7% (38) 61.1% (11) 39.1% (27) 0.094 Endovascular treatment 33.3% (29) 50% (9) 29% (20) 0.092 Left atrial diameter, cm [IQR] 4.0 [3.7À4.6] 4.5 [4.0À4.9] 4.0 [3.6À4.5] 0.043 Left atrial area, cm2 [IQR] 20.0 [15.6À23.0] 22.3 [20.2À26.2] 18.6 [15.0À23.0] 0.001 AF = atrial fibrillation; IQR = interquartile range; MSE = main source of embolism; NIHSS = National Institutes of Health Stroke Scale/Score (moderate to severe stroke, NIHSS 8). ARTICLE IN PRESS 4 Ultrasound in Medicine Biology Volume 00, Number 00, 2020
  5. 5. diagnosis of non-obstructive thrombosis in patients known to have a prosthetic valve. Sensitivity analysis and validation are outlined in Table 3. The overall agreement between HHE and TTE was 0.95, and with respect to each MSE type, 0.93 for SVD and 0.92 for EV. Among the cases SVD, 22.2% (4/ 18) had transient embolic sources. Figure 2 illustrates a left ventricle thrombus and a right atrial thrombus. Table 2 summarizes the baseline characteristics of 104 patients with unknown stroke etiology. MSEs were detected in 16% (17/104); in all cases anticoagulation was started as secondary prevention treatment. Anticoa- gulation was initiated within the first 48 h of stroke onset in 41% of cases (7/17). We did not observe intracranial bleeding or any other related problems. Coronary artery disease (35.3% vs. 12.6%, p = 0.021) and chronic heart failure (52.9% vs. 6.8%, p 0.001) were more prevalent in patients diagnosed with MSEs. According to stroke characteristics, LVO was more commonly observed in patients with MSEs (82.4% vs. 48% p = 0.010). Also, patients in whom MSEs were detected more frequently underwent intravenous fibrinolysis (76.5% vs. 43.7%, p = 0. 01). Multivariate analysis indicated that LVO (odds ratio [OR]: 4.24, 95% confidence interval [CI]: 1.01À17.85) and previous chronic heart failure (OR: 13.25, 95% CI: 3.54À49.50) were independent predic- tors of MSEs. Of 87 patients with undetermined stroke and no MSE detection, we observed that the global rate of AF detection was 20% (18/87) (Table 1). These patients were older, 79 y versus 72 y (p = 0.003), and had more severe strokes according to NIHSS score (11 points vs. 6 points, p = 0.016). Also, LVO (83.3% vs. 39.1%, p = 0.001) was more prevalent. Regarding HHE characteris- tics, LA diameter and LA area were greater in patients in whom AF was detected (4.5 cm vs. 4 cm, p = 0.043, and 22.3 cm2 vs. 18.6 cm2 , p = 0.001, respectively). The area under the ROC curve was 0.74 (95% CI: 0.64À0.85) for LA area to detect AF, and the best cutoff point to detect AF was LA area 20 cm2 , yielding a sensitivity of 83.3% and a specificity of 62.7%. Almost half of the cases of undetermined strokes without MSE detection (40/87) were patients with an LA area 20 cm2 by HHE. AF was detected in 37.5% of these patients (15/40) with enlarged LA area, as illustrated in Figure 1. Multivariate logistic regression analysis indicated that LVO (OR: 6.54, 95% CI: 1.62À26.27) and LA area 20 cm2 (OR: 7.01, 95% CI: Table 2. Baseline characteristics of unknown stroke etiology All (n = 104) MSE (n = 17) No MSE (n = 87) p Value Age, median [IQR] 74 [61À81] 67 [55À78] 76 [63À82] 0.123 Sex (female) 50% (52) 35.3% (6) 52.9% (46) 0.185 Hypertension 71.15% (74) 64. 7% (11) 72. 4% (63) 0.382 Diabetes mellitus 24.0% (25) 35. 3% (6) 21.83% (19) 0.257 Dyslipidemia 50% (52) 35.3% (6) 52.8% (46) 0.156 Former or past smoker 28.8%(30) 47% (8) 25.2% (22) 0.080 Coronary artery disease 16.3% (17) 35.3% (6) 12.6% (11) 0.021 Chronic heart failure 14.4% (15) 52.9% ( 9) 6.8% ( 6) 0.001 Previous stroke 17. 3% (18 ) 11.8% (2) 18.3% (16) 0.486 NIHSS, median [IQR] 8 (3.0À14.0) 9 (6.0À15.5) 7 (3.0À14.0) 0.309 Mild strokes 52.9% (55) 35.3% (6) 56.3% (49) 0.112 Moderate to severe stroke 47.1% (49) 64.7% (11) 43.7% ( 38) 0.112 Large vessel occlusion 53.8% (56) 82.4% (14) 48.3% (42) 0.010 Intravenous alteplase 49% (51) 76.5% (13) 43.7% (38) 0.013 Endovascular treatment 34.6% (36) 41.2% (7) 33.3% (29) 0.534 AF = atrial fibrillation; IQR = interquartile range; MSE = main sources of embolism; NIHSS = National Institutes of Health Stroke Scale/Score (moderate to severe stroke, NIHSS 8). *Results are expressed as the percentage (number) of cases unless otherwise indicated. y “No MSE” describes patients with strokes of undetermined etiology without diagnosis of main sources of embolism with point-of-care ultrasound. Table 3. Agreement and accuracy of acute HHE and conventional transthoracic echocardiography (N = 130) N (%) k Sensitivity Specificity PPV NPV MSEs 25 (19.23) 0.95 (0.88À1.0) 96.00 (77.68À99.79) 99.05 (94.04À99.95) 96.00 (77.68%À99.79) 99.05 (94.04À99.95) SVD 18y (13.85) 0.93 (0.84À1) 94.44 (70.62À99.71) 99.11 (94.40À99.95) 94.44 (70.62À99.71) 99.11 (94.40À99.95) EV 8y (6.15) 0.92 (0.79À1) 87.50 (47.35À99.68) 100 (97.02À100) 100 (59.04À100) 99.19 (95.55À99.98) EV = embolic valvulopathy; HHE = hand-held echocardiography; MSE = main sources of embolism; NPV = negative predictive value; PPV = pos- itive predictive value; SVD = severe ventricular dysfunction; k = kappa concordance coefficient *Results are expressed as the percentage (number) of cases. y One patient had SVD and EV simultaneously. ARTICLE IN PRESS Hand-held echocardiography as POCUS in acute ischemic stroke J. JUEGA et al. 5
  6. 6. 1.75À28.09) were both independently associated with detection of AF. DISCUSSION We evaluated HHE in the detection of sources of embolism in the acute phase of stroke as early as possi- ble. Previous work revealed that POCUS is feasible, enabling reliable quantification of cardiac parameters in stroke patients (Kraft et al. 2017); however, our study is the first experiment designed for POCUS in the acute phase of stroke. The implementation of ultraportable devices allows the performance of studies not only at the bedside of the patient, but also in the CT or angiography suite. Images and loops of video can be stored for cardi- ology to review. Also, stored data can be exported for offline expert interpretation (Singh et al. 2013). Our protocol was designed to prioritize emergent stroke reperfusion treatment. Therefore, POCUS may help to detect SVD or EV once acute reperfusion treat- ment is performed. Because ’’time is brain,’’ POCUS has been scheduled after reperfusion treatment. The advantage of such early screening is the possibility of detecting an embolic source that may not be diagnosed later. Some researchers have stated that the rate of thrombus detected by TTE in patients with ischemic stroke is low (Abreu et al. 2005). We assume that an intracardiac thrombus may disappear and not be detected in the post-acute phase. The validation study revealed that HHE is reliable in detecting MSEs when compared with TTE. The number of misdiagnoses was pretty low. Our protocol was not designed to study complex aortic atheromatosis or patent foramen ovale, which may require TEE beyond the acute phase of the stroke. Fig. 2. Thrombi in cardiac chambers diagnosed by point-of-care ultrasound scanning. (a, c) Left ventricle thrombus (white arrow) in parasternal short-axis view (a) and apical four-chamber view (b). (c, d) Right atrial thrombus (white arrow) in apical four-chamber view (c) and subcostal view (d) ARTICLE IN PRESS 6 Ultrasound in Medicine Biology Volume 00, Number 00, 2020
  7. 7. In our protocol, we focused HHE on finding MSEs to anticipate the detection of potential causes of stroke that deserve anticoagulation for secondary prevention. In our study, the MSE diagnostic yield was considerable, as we detected MSEs in nearly 1 in 5 patients evaluated. Regarding patients with undetermined stroke, 16% (17/ 104) were new MSE diagnoses. We found that LVO and chronic heart disease were independent predictors of MSE detection; therefore, HHE should be prioritized in patients with LVO and chronic heart disease based on our data. The main cover cause is AF in patients with unde- termined stroke, which means AF screening should be performed in all patients with cryptogenic stroke. Some authors suggest new diagnostic methods to improve the diagnostic yield in the shortest time after stroke (Sposato et al. 2015). Latest stroke guidelines recommend 30-d rhythm monitoring without delay if no other apparent cause has been detected (Kernan et al. 2014). HHE may help to select patients to start earlier inpatient cardiac monitoring and to prolong the monitoring with devices such as external or implantable recorders once conven- tional AF screening (electrocardiogram, cardiac teleme- try) has been performed. Our hypothesis is that MSEs and hidden undiagnosed AF in patients with enlarged left atria were linked to LVO because large thrombi could be formed inside cardiac chambers. On the basis of our treatment protocol there was a therapeutic impact after HHE in 30.76% (32/104) of patients. MSEs were detected in 17 cases and 15 patients with an LA area 20 cm2 were diagnosed with AF. Our treatment protocol calls for anticoagulation starting in the first 48 h after stroke. This was the case in almost half of the patients with MSEs. Our study was not designed to evaluate this treatment. Randomly allo- cated, controlled trials to assess the optimal time to initi- ate anticoagulation after acute stroke are underway (Smythe et al., 2020). Limitations The study has certain limitations. The considerable prevalence of MSEs could be justified by the characteris- tics of the study population. The high prevalence of severe strokes evaluated may have influenced the high positive and negative predictive values. On the other hand, the study was carried out with patients in the supine position to avoid treatment delay, which may have influenced the quality of the registry and increased the percentage of patients with a poor thoracic window. Still, less than 10% of patients (14/156) were excluded only because of a poor thoracic window. This work should be used only as primary experience in MSE detection with HHE in the acute phase of stroke, and its results should be confirmed by other studies before mak- ing further recommendations. CONCLUSIONS Patients with LVO and chronic heart disease may benefit from HHE as part of point-of-care ultrasound in the acute phase of ischemic stroke. The left atrial area measured was an independent predictor of AF in strokes of undetermined etiology. Acknowledgments—This work was supported by the Research Fund of the Spanish Society of Neurology (SEN) through the Spanish Society of Neurosonology (SONES). Conflict of interest disclosure—The authors declare no competing interests. REFERENCES Abreu TT, Mateus S, Correia J. Therapy implications of transthoracic echocardiography in acute ischemic stroke patients. Stroke 2005;36:1565–1566. Adams HP, Jr, Bendixen BH, Kappelle, Biller J, Love BB, Gordon DL, Marsh EE. Classification of subtype of acute ischemic stroke: Defi- nitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41. Amiel JB, Gru¨mann A, Lheritier G, Clavel M, Fran¸cois B, Pichon N, Dugard A, Marin B, Vignon P. Assessment of left ventricular ejec- tion fraction using an ultrasonic stethoscope in critically ill patients. Crit Care 2012;16:R29. Arboix A, Alio J. Acute cardioembolic cerebral infarction: answers to clinical questions. Curr Cardiol Rev 2012;8:54–67. Bersano A, Melchiorre P, Moschwitis G, Tavarini F, Cereda C, Micieli G, Parati E, Bassetti C. Tako-tsubo syndrome as a consequence and cause of stroke. Funct Neurol 2014;29:135–137. Cardim N, Dalen H, Voigt JU, Ionescu A, Price S, Neskovic AN, Edvardsen T, Galderisi M, Sicari R, Donal E, Stefanidis A, Del- gado V, Zamorano J, Popescu BA. The use of handheld ultrasound devices: a position statement of the European Association of Car- diovascular Imaging (2018 update). Eur Heart J Cardiovasc Imag- ing 2019;20:245–252. Evangelista A, Galuppo V, Mendez J, Evangelista L, Arpal L, Rubio C, Vergara M, Liceran M, Lopez F, Sales C, Miralles V, Galinsoga A, Perez J, Arteaga M, Salvador B, Lopez C, Garcıa-Dorado D. Hand- held cardiac ultrasound screening performed by family doctors with remote expert support interpretation. Heart 2016;102:376– 382. Ferreira JP, Girerd N, Gregson J, Latar I, Sharma A, Pfeffer MA, McMurray JJV, Abdul-Rahim AH, Pitt B, Dickstein K, Rossignol P, Zannad F. Stroke risk in patients with reduced ejection fraction after myocardial infarction without atrial fibrillation. J Am Coll Cardiol 2018;71:727–735. Habib G, Badano L, Tribouilloy C, Vilacosta I, Zamorano JL, Galderisi M, Voigt JU, Sicari R, Cosyns B, Fox K, Aakhus S. Recommenda- tions for the practice of echocardiography in infective endocarditis. Eur J Echocardiogr 2010;11:202–219. Jordan K, Yaghi S, Poppas A, Chang AD, MacGrory B, Cutting S, Bur- ton T, Jayaraman M, Tsivgoulis G, Sabeh MK, Merkler AE, Kamel H, Elkind MSV, Furie K, Song C. Left atrial volume index is asso- ciated with cardioembolic stroke and atrial fibrillation detection after embolic stroke of undetermined source. Stroke 2019;50:1997–2001. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchel PH, Rich MW, Richardson D, Schwamm LH, Wilson JA. American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing Council on Clinical Cardiology, and Council on Peripheral Vascular Dis- ease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline for healthcare professio- nals from the American Heart Association/American Stroke Asso- ciation. Stroke 2014;45:2160–2236. ARTICLE IN PRESS Hand-held echocardiography as POCUS in acute ischemic stroke J. JUEGA et al. 7
  8. 8. Kraft P, Fleischer A, Wiedmann S, Ru¨cker V, Mackenrodt D, Morbach C, Malzahn U, Kleinschnitz C, St€ork S, Heuschmann PU. Feasibil- ity and diagnostic accuracy of point-of-care handheld echocardiog- raphy in acute ischemic stroke patients—A pilot study. BMC Neurol 2017;17:159. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancel- lotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Associa- tion of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015;16:233–270. Leslie-Mazwi T, Chandra RV, Baxter BW, Arthur AS, Hussain MS, Singh IP, Frei DF, Klucznik RP, Albuquerque FC, Hirsch JA. ELVO: an operational definition. J Neurointerv Surg 2018;10:507– 509. Muchada M, Rubiera M, Rodriguez-Luna D, Pagola J, Flores A, Kallas J, Sanjuan, Meler P, Alvarez-Sabin J, Ribo M, Molina CA, et al. Baseline National Institutes of Health stroke scale-adjusted time window for intravenous tissue-type plasminogen activator in acute ischemic stroke. Stroke 2014;45:1059–1063. Pagola J, Gonzalez-Alujas T, Muchada M, Teixido G, Flores A, De Blauwe S, Sero L, Luna DR, Rubiera M, Ribo M, Boned S, Alvarez-Sabin J, Evangelista A, Molina CA. Stroke Echoscan pro- tocol: A fast and accurate pathway to diagnose embolic strokes. J Neuroimaging 2015;25:365. Pagola J, Juega J, Francisco-Pascual J, Moya A, Sanchis M, Busta- mante A, Penalba A, Usero M, Cortijo E, Arenillas JF, Calleja AI, Sandin-Fuentes M, Rubio J, Mancha F, Escudero-Martinez I, Moniche F, de Torres R, Perez-Sanchez S, Gonzalez-Matos CE, Vega A, Pedrote AA, Arana-Rueda E, Montaner J, Molina CA. Yield of atrial fibrillation detection with textile wearable holter from the acute phase of stroke: Pilot study of Crypto-AF registry. Int J Cardiol 2017;251:45–50. Pepi M, Evangelista A, Nihoyannopoulos P, Flachskampf FA, Athanas- sopoulos G, Colonna P, Habib G, Ringelstein EB, Sicari R, Zamor- ano JL, Sitges M, Caso P. Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embo- lism: European Association of Echocardiography (EAE) (a regis- tered branch of the ESC). Eur J Echocardiogr 2010;11:461–476. Perez de Isla L, Dıaz Sanchez S, Pagola J, Garcıa de Casasola Sanchez G, Lopez Fernandez T, Sanchez Barrancos IM, Martınez-Sanchez P, Zapatero Gaviria A, Anguita M, Ruiz Serrano AL, Torres Macho J. Consensus Document of the SEMI, semFYC, SEN, and SEC on Focused Cardiac Ultrasound in Spain. Rev Esp Cardiol (Engl Ed) 2018;71:935–940. Popescu BA, Andrade MJ, Badano LP, Fox KF, Flachskampf FA, Lan- cellotti P, Varga A, Sicari R, Evangelista A, Nihoyannopoulos P, Zamorano JL, European Association of Echocardiography, Deru- meaux G, Kasprzak JD, Roelandt JR. European Association of Echocardiography recommendations for training, competence, and quality improvement in echocardiography. Eur J Echocardiogr 2009;10:893–905. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. 2018 guidelines for the early management of patients with acute ische- mic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2018;49:e46–e110. Ribo M, Boned S, Rubiera M, Tomasello A, Coscojuela P, Hernandez D, Pagola J, Juega J, Rodriguez N, Muchada M, Rodriguez-Luna D, Molina CA. Direct transfer to angiosuite to reduce door-to-punc- ture time in thrombectomy for acute stroke. J Neurointerv Surg 2017;10:221–224. Sala-Padro J, Pagola J, Gonzalez-Alujas MT, Sero L, Juega J, Rodri- guez-Villatoro N, Boned S, Rodriguez-Luna D, Muchada M, Fer- nandez-Galera R, Rubiera M, Ribo M, Evangelista A, Molina C. Prosthetic valve thrombosis in the acute phase of the stroke: Rele- vance of detection and follow-up. J Stroke Cerebrovasc Dis 2017;26:1110–1113. Saric M, Armour AC, Arnaout MS, Chaudhry FA, Grimm RA, Kron- zon I, Landeck BF, Maganti K, Michelena HI, Tolstrup K. Guide- lines for the use of echocardiography in the evaluation of a cardiac source of embolism. J Am Soc Echocardiogr 2016;29:1–42. Singh S, Bansal M, Maheshwari P, Adams D, Sengupta SP, Price R, Dantin L, Smith M, Kasliwal RR, Pellikka PA, Thomas JD, Narula J, Sengupta PP, ASE-REWARD Study Investigators. American Society of Echocardiography: Remote echocardiography with web- based assessments for referrals at a distance (ASE-REWARD) Study. J Am Soc Echocardiogr 2013;26:221–233. Smythe MA, Parker D, Garwood CL, Cuker A, Messe SR. Timing of initiation of oral anticoagulation after acute ischemic stroke in patients with atrial fibrillation. Pharmacotherapy 2020;40: 55–71. Sposato LA, Cipriano LE, Saposnik G, Ruız Vargas E, Riccio PM, Hachinski V. Diagnosis of atrial fibrillation after stroke and tran- sient ischaemic attack: A systematic review and meta-analysis. Lancet Neurol 2015;14:377–387. Yang H, Nassif M, Khairy P, de Groot JR, Roos YBWEM, de Winter RJ, Mulder BJM, Bouma BJ. Cardiac diagnostic work-up of ischae- mic stroke. Eur Heart J 2018;39:1851–1860. ARTICLE IN PRESS 8 Ultrasound in Medicine Biology Volume 00, Number 00, 2020