Seamens’ Sign: A Novel Electrocardiogram Prediction Tool for Left Ventricular Hypertrophy

Seamens’ Sign: A Novel Electrocardiogram Prediction Tool for Left Ventricular Hypertrophy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Seamens’ Sign: A Novel Electrocardiogram Prediction Tool for Left Ventricular Hypertrophy Philip Walker, Cathy Jenkins, Jeremy Hatcher, Clifford Freeman, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-539457/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Study Objective: We developed a novel, quick, easy to use electrocardiogram (ECG) screening criterion (Seamens’ Sign) for left ventricular hypertrophy (LVH). This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads. Methods: This study was a retrospective chart review of 2184 patient records. The primary outcome was whether Seamens’ Sign was noninferior in confirming LVH compared to other common criteria. Test characteristics were calculated for each of the LVH criteria. Inter-rater agreement was assessed on a random sample using Cohen’s Kappa. Results: Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by transthoracic echocardiogram (TTE). Nine percent were positive for LVH on ECG based on Seamens’ Sign. Seamens’ Sign had a specificity of 0.92. Tests assessing noninferiority indicated Seamens’ Sign was non-inferior to all criteria (p < 0.001) except for Cornell criterion for women (p = 0.98). Seamens’ Sign had 90% (0.81-1.00) inter-rater agreement, the highest of all criteria in this study. Conclusion: When compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens’ Sign is noninferior in ruling in LVH on ECG. Additionally, Seamens’ Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, perhaps related to its ease of use. Critical Care & Emergency Medicine Biostatistics General Surgery Electrocardiogram electrocardiography left ventricular hypertrophy emergency medicine Figures Figure 1 1.0 Background Patients with left ventricular hypertrophy (LVH) diagnosed by electrocardiogram (ECG) have increased mortality and a higher risk for life-threatening cardiovascular disease, most commonly coronary artery disease in men and heart failure in women. , LVH is commonly diagnosed via ECG in the emergency department (ED), often in cardiac workup or incidentally. These LVH diagnoses provide evidence of patients’ overall cardiovascular health and inform cardiac risk management and stratification. The process of diagnosing LVH is multi-faceted. Cardiac echocardiography or left ventricular mass measurements via cardiac magnetic resonance imaging (MRI) are the gold standards , . However, widespread LVH screening via these methods is neither feasible nor cost effective. ECGs performed in the ED setting offer an opportunity to identify patients with increased risk for cardiac mortality and who are candidates for potential risk-modifying therapy. Despite the importance of efficient, accurate LVH prediction based on ECGs, commonly used methods have known diagnostic test inaccuracies and are challenging to use. Most current criteria require measuring or adding varying lead voltages, and may be complicated by risk of calculation errors. There are numerous ECG criteria for identifying LVH, with varying tests characteristics influenced by underlying cardiac conduction defects, gender, race, and body habitus. , , Ultimately, ECG diagnostic criteria for LVH are clinically lacking. Though many attempts at defining more sensitive and specific ECG criteria for LVH have been proposed, none approach the accuracy of gold-standard imaging modalities . These proposed criteria generally increase complexity to marginally improve sensitivity and/or specificity, creating a barrier to quick application in the ED setting. Instead of more complex ECG criteria, we propose a novel, quick, and easily recognizable screening criterion for LVH can be learned with little memorization and applied in a fast-paced setting. The proposed criterion— “Seamens’ Sign”—involves one question: do any of the QRS complexes in the precordial leads of a standard 12-lead ECG touch or cross another QRS complex (e.g., V1 QRS complex touching/crossing V2 QRS complex) (Fig. 1)? From an electrophysiologic standpoint, many reasons explain why precordial lead QRS complex touching/overlap works for LVH detection. Typical, non-pathologic R wave progression in the precordial leads shows that as the electrical signal passes from the sinoatrial node towards the apex of the left ventricle, prominent S waves (overall negative deflection) in V1 and V2 transition to predominant R waves (overall positive deflection) in V5 and V6. As the left ventricle hypertrophies, changes occur leading to an electrical vector of greater magnitude, translating to increased amplitude of the S and R waves in the precordial leads, often leading to the precordial QRS complexes touching or overlapping. , In this study, we evaluated the test characteristics of the proposed Seamens’ Sign and compared its ability to confirm an LVH diagnosis against three of the most used voltage criteria today (two Sokolow-Lyon criteria and the Cornell Criteria). 2.0 Methods 2.1 Study Design This study was an electronic health record (EHR) retrospective chart review at a quaternary care academic medical center. The data collection period included clinical tests performed 5 July 2019 through 14 January 2020 as part of routine ED care. 2.2 Eligibility A query of the EHR was performed, identifying patients with both an ECG and a transthoracic echocardiogram (TTE) performed within 90 days of each other. No patients were excluded prior to data analysis on the basis of age, ethnicity, comorbidities, co-existing cardiac diagnoses evident on ECG or TTE, or other clinical factors. 2.3 Data Collection & ECG Coding Total sample size for chart review was determined based on the number of subjects needed to estimate the sensitivity of Seamens’ Sign to a pre-specified margin of error. A total of 2184 patient records were reviewed based on estimating a hypothesized sensitivity of 65% to a 2% margin of error. Data gathered during the initial EHR query included age, sex, ECG time/date, and TTE time/date. Each patient chart was assembled by an initial set of reviewers (primarily third year medical students), and assigned a random study number. They downloaded a copy of the ECG labeled with the study number and with all patient identifiers removed. They reviewed the TTE report and recorded whether or not LVH was identified. LVH was defined as any mention of the patient having concentric LVH in the TTE report. Septal or other focal hypertrophy was not considered LVH. A second, independent set of blinded reviewers (Emergency Medicine residents) reviewed each ECG for signs of LVH based on two Sokolow-Lyon criteria, the Cornell criteria, and the study criterion, Seamens’ Sign. The first criterion, noted as the Sokolow-Lyon 1 criterion (SL-1) was defined as the S wave in lead V1 plus the R wave in lead V5 or V6 (using larger R wave in V5 or V6) being greater than or equal to 35mm. The second Sokolow-Lyon criterion, noted as Sokolow-Lyon 2 criterion (SL-2), was defined as the R wave in lead aVL being greater than or equal to 11mm. The Cornell criteria were defined as the S wave in lead V3 plus the R wave in lead aVL being greater than 28mm in males or greater than 20mm in females. These criteria’s test characteristics were compared against the test characteristics for the proposed new criterion, Seamens’ Sign. This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads (lead V1 QRS complex touching/crossing lead V2 QRS complex, or lead V2 QRS complex touching/crossing lead V3 QRS complex, or lead V4 QRS complex touching/crossing lead V5 QRS complex, or lead V5 QRS complex touching/crossing lead V6 QRS complex). 2.4 Outcome Measures The primary outcome was determining whether Seamens’ Sign was noninferior in confirming LVH compared to the other criteria. 2.5 Analysis Diagnosis of concentric LVH by TTE was considered the gold standard against which the various ECG criteria for LVH were compared to determine sensitivity and specificity. Descriptive statistics of demographic and clinical characteristics were computed for the study population. Test characteristics, including sensitivity, specificity, and positive and negative predictive values, along with their 95% confidence intervals, were calculated for each of the LVH criteria. Non-inferiority of Seamens’ Sign criterion compared to the Cornell and Sokolow-Lyon criteria was evaluated using a method designed for paired binary data. The margin of non-inferiority was pre-specified at 5% (p = 0.05). To compare Cornell criteria for men and women to those with Seamens’ Sign, only men with Seamens’ Sign were compared to other men meeting Cornell criteria, and the same method was used for women. To ensure validity of reviewer ECG coding and assess ease of interpretation, inter-rater agreement was assessed on a random sample using Cohen’s Kappa with the 95% confidence intervals. All statistical analyses were performed using R statistical programming language, Version 3.5.2. 3.0 Results 3.1 Patient Characteristics Patient characteristics are listed in Table 1 . Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by TTE. The vast majority of TTEs were performed within 1 day of ECGs, with the median of 1 day, and the interquartile range of 0 to 21 days. Nine percent were positive for LVH on ECG based on Seamens’ Sign, and 3% and 7% were positive for LVH on ECG based on Sokolow-Lyon 1 and Sokolow-Lyon 2 criteria, respectively. There were 7% of men and 13% of women positive for LVH on ECG based on Cornell criteria. Table 1 Descriptive statistics on demographic and clinical characteristics of the cohort. N is the number of non-missing values. Numbers after proportions are frequencies, with the exception of age and ECG to TTE. Age and ECG to TTE are reported as the median, with following numbers the lower and upper interquartile for these continuous variables. N N = 2184 Age 2184 63 (51, 73) Sex 2184 Male 52% (1135) Female 48% (1049) TTE for LVH (gold standard) 2184 No 65% (1428) Yes 35% (756) ECG to TTE (days) 2184 1 (0, 21) Seamens' Sign positive for LVH 2184 No 91% (1994) Yes 9% (190) Sokolow-Lyon 1 positive for LVH 2184 No 97% (2113) Yes 3% (71) Sokolow-Lyon 2 positive for LVH 2184 No 93% (2037) Yes 7% (147) Cornell (overall) positive for LVH 2184 No 90% (1971) Yes 10% (213) Cornell (men) positive for LVH 1135 No 93% (1056) Yes 7% (79) Cornell (women) positive for LVH 1049 No 87% (914) Yes 13% (135) 3.2 Sensitivity and Specificity Test characteristics are presented in Table 2 . Specificities ranged from 0.89 for the Cornell criterion for women to 0.98 for the Sokolow-Lyon 1 criterion, with Seamens’ Sign having a specificity of 0.92. Table 2 Test characteristics for Seamens’ Sign criterion, Sokolow-Lyon 1 (SL-1) and 2 (SL-2) criteria, and Cornell criteria for diagnosing left ventricular hypertrophy from electrocardiograms. Sensitivity Specificity PPV NPV Test Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI Seamens' Sign 0.11 (0.09, 0.13) 0.92 (0.91, 0.94) 0.43 (0.36, 0.51) 0.66 (0.64, 0.68) SL-1 0.05 (0.03, 0.07) 0.98 (0.97, 0.98) 0.51 (0.39, 0.63) 0.66 (0.64, 0.68) SL-2 0.08 (0.06, 0.10) 0.94 (0.93, 0.95) 0.41 (0.33, 0.50) 0.66 (0.64, 0.68) Cornell Overall 0.13 (0.11, 0.15) 0.92 (0.90, 0.93) 0.46 (0.39, 0.52) 0.67 (0.64, 0.69) Cornell Men 0.09 (0.07, 0.12) 0.94 (0.92, 0.96) 0.51 (0.39, 0.62) 0.62 (0.59, 0.65) Cornell Women 0.18 (0.14, 0.23) 0.89 (0.87, 0.91) 0.42 (0.34, 0.51) 0.71 (0.68, 0.74) 3.4 Non-Inferiority Tests assessing noninferiority indicated Seamens’ Sign was non-inferior to all criteria (p < 0.001) except for Cornell criterion for women (p = 0.98) (Table 3 ). Table 3 p-values for tests assessing non-inferiority of Seamens’ Sign when compared to other commonly used tests. Comparison P Sokolow-Lyon 1 < 0.001 Sokolow-Lyon 2 < 0.001 Cornell Overall < 0.001 Cornell Men < 0.001 Cornell Women 0.98 3.3 Inter-Rater Agreement Inter-rater agreement was assessed on 250 subjects using Cohen’s Kappa statistic and a 95% confidence interval (Table 4 ). Seamens’ Sign had 90% (0.81-1.00) agreement, the highest of all criteria, attributed to its quick application and ease of use. Sokolow-Lyon 1 and Sokolow-Lyon 2 had inter-rater agreement of 65% (0.40–0.91) and 87% (0.75-1.00) respectively. Sokolow-Lyon 1 likely has lower inter-rater agreement secondary to multiple leads used and subjectivity in selecting the R wave in lead V5 or V6. Cornell criteria for men and women had inter-rater agreements of 76% (0.56–0.96) and 79% (0.62–0.97), respectively. Table 4 Inter-rater agreement using Cohen’s Kappa with 95% confidence interval. Test Kappa 95% CI Seamens' Sign 0.9 (0.81, 1.00) Sokolow-Lyon 1 0.65 (0.40, 0.91) Sokolow-Lyon 2 0.87 (0.75, 1.00) Cornell Overall 0.82 (0.69, 0.94) Cornell (Men) 0.76 (0.56, 0.96) Cornell (Women) 0.79 (0.62, 0.97) 4.0 Discussion While modalities other than ECG are the gold-standard for diagnosing LVH, it is important to account for their difficulty and cost compared to the quick, easy to obtain, and inexpensive ECG, particularly in emergency care settings. Furthermore, there are data suggesting LVH diagnosed by ECG criteria represents a clinically distinct entity, and has been associated with increased mortality and other pathologic conditions. This furthers the argument of the importance of fast, reliable methods of diagnosing LVH by ECG. This analysis suggests Seamens’ Sign is non-inferior to other methods of evaluating LVH on ECG, and has high inter-rater agreement. It is easy to perform quickly without a measurement device or need for any calculations at all. Given these findings, we believe that Seamens’ Sign is easily applicable in emergency care settings and can facilitate the diagnosis of LVH, potentially leading to decreased cardiac morbidity and mortality. 4.1 Strengths This is a large study comparing test characteristics of multiple criteria to Seamens' Sign. Three of the most widely used criteria were chosen to model real-world application. Compared to most prior studies, the number of subjects analyzed was larger. Of the prior 14 studies analyzing ECG diagnosis of LVH, enrollment ranged from 94 to 5608 patients; this study is the third largest. Those interpreting ECGs were blinded from the TTE results to remove any bias. The proliferative phase of cardiac remodeling takes place within the first 2–7 days after a myocardial infarction, transitioning to the maturing phase around day 7. Based on these findings, a 90-day limit on the time difference between the TTE and ECG dates was placed to reduce the likelihood of cardiac remodeling affecting results. The majority of the ECGs and TTEs were performed within 1 day of each other, limiting the chances of cardiac remodeling affecting the ECG or TTE. 4.2 Limitations While Seamens’ Sign is a quick, effective, reliable alternative to other criteria for diagnosing LVH on ECG, there are study limitations. All ECGs were included, without removal of bundle branch blocks or other abnormal findings that could alter the results. However, this limitation was applied across all criteria in the study, helping to eliminate any differences in their application. Also, with the exception of the Cornell criteria which differentiates between sexes, we did not differentiate the application of the other criteria based on sex. This could hide differences in application of the criteria between sexes, but stays true to original application of these criteria. There were no changes in application of criteria based on age. There are known differences in ECG appearance based on age, including potential QRS amplitude changes. Finally, since this was a retrospective study, there were multiple providers obtaining ECGs, multiple echocardiographers performing the TTEs, and multiple cardiologists reading the TTEs, which could lead to variability in ECG and TTE acquisition, interpretation, and reporting of LVH. 5.0 Conclusion When compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens’ Sign is noninferior in confirming LVH on ECG. Additionally, Seamens’ Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, possibly related to its ease of use. 6.0 Declarations 6.1 Ethics approval and consent to participate This study (IRB#200150) was approved by the Vanderbilt Institutional Review Board and Human Research Protections Program as an exempt study that poses minimal risk to participants given it only involved retrospective chart review. The informed consent for this study is waived by the Vanderbilt Institutional Review Board due to retrospective nature. All methods were performed in accordance with the relevant guidelines and regulations. 6.2 Consent for publication The informed consent for this study is waived by the Vanderbilt Institutional Review Board due to retrospective nature. 6.3 Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due being secured in a private, password protected, Vanderbilt University Medical Center (VUMC) repository only available to VUMC employees, but are available from the corresponding author on reasonable request. 6.4 Competing interests The authors declare that they have no competing interests. 6.5 Funding There was no internal or external funding for this research study. 6.6 Authors' contributions PWW, NM, ABS, CAJ, and CS conceived and designed the study. PWW, NM, and ABS were responsible for drafting and obtaining IRB approval. PWW and NM supervised data collection and conduction of the study. CAJ provided statistical advice on study design and analyzed the data. JBS, EH, CM, TR, LCW, TP, RP, AA, OH, JO, and AK were the primary initial chart reviewers. CLF, NS, and BR were the second set of blinded reviewers. PWW drafted the manuscript, and all authors contributed substantially to its revision. PWW takes responsibility for the paper as a whole. 6.7 Acknowledgements Not applicable 7.0 List Of Abbreviations ECG—Electrocardiogram ED—Emergency department EHR—Electronic health record LVH—Left ventricular hypertrophy MRI—Magnetic resonance imaging NPV—Negative predictive value PPV—Positive predictive value SL-1—Sokolow-Lyon 1 criterion SL-2—Sokolow-Lyon 2 criterion TTE—Transthoracic echocardiogram References Sundström J, Lind L, Arnlöv J, Zethelius B, Andrén B, Lithell HO. Echocardiographic and electrocardiographic diagnoses of left ventricular hypertrophy predict mortality independently of each other in a population of elderly men. Circulation. 2001;103(19):2346-51. Desai CS, Ning H, Lloyd-jones DM. Competing cardiovascular outcomes associated with electrocardiographic left ventricular hypertrophy: the Atherosclerosis Risk in Communities Study. Heart. 2012;98(4):330-4. Bacharova L, Estes EH. Left Ventricular Hypertrophy by the Surface ECG. J Electrocardiol. 2017;50(6):906-908. Lang RM, Badano LP, Mor-avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14. Zhang W, Zhou Y, Bai B, et al. Consistency of left ventricular hypertrophy diagnosed by electrocardiography and echocardiography: the Northern Shanghai Study. Clin Interv Aging. 2019;14:549-556. Hedman K, Moneghetti KJ, Hsu D, et al. Limitations of Electrocardiography for Detecting Left Ventricular Hypertrophy or Concentric Remodeling in Athletes. Am J Med. 2020;133(1):123-132.e8. Antikainen RL, Grodzicki T, Palmer AJ, et al. Left ventricular hypertrophy determined by Sokolow-Lyon criteria: a different predictor in women than in men?. J Hum Hypertens. 2006;20(6):451-9. Jaggy C, Perret F, Bovet P, et al. Performance of classic electrocardiographic criteria for left ventricular hypertrophy in an African population. Hypertension. 2000;36(1):54-61. Germano G. Electrocardiographic signs of left ventricular hypertrophy in obese patients: what criteria should be used?. High Blood Press Cardiovasc Prev. 2015;22(1):5-9. Mahn JJ, Dubey E, Brody A, et al. Test characteristics of electrocardiography for detection of left ventricular hypertrophy in asymptomatic emergency department patients with hypertension. Acad Emerg Med. 2014;21(9):996-1002. Hill JA. Hypertrophic reprogramming of the left ventricle: translation to the ECG. J Electrocardiol. 2012;45(6):624-629. Bacharova L, Szathmary V, Kovalcik M, Mateasik A. Effect of changes in left ventricular anatomy and conduction velocity on the QRS voltage and morphology in left ventricular hypertrophy: a model study. J Electrocardiol. 2010;43(3):200-208. Liu JP, Hsueh HM, Hsieh E, Chen JJ. Tests for equivalence or non-inferiority for paired binary data. Stat Med. 2002;21(2):231-45. Aro AL, Chugh SS. Clinical diagnosis of electrical versus anatomic left ventricular hypertrophy: prognostic and therapeutic implications. Circ Arrhythm Electrophysiol. 2016;9(4):e003629. French BA, Kramer CM. Mechanisms of post-infarct left ventricular remodeling. Drug Discov Today Dis Mech. 2007;4(3):185-196. Levy D, Bailey JJ, Garrison RJ, et al. Electrocardiographic changes with advancing age. A cross-sectional study of the association of age with QRS axis, duration and voltage. J Electrocardiol. 1987;20 Suppl:44-47. Additional Declarations No competing interests reported. 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Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Olivia","middleName":"","lastName":"Henry","suffix":""},{"id":29775105,"identity":"542f93bf-2369-457f-b090-055116ce7b89","order_by":14,"name":"Jessica O'Shea","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"O'Shea","suffix":""},{"id":29775106,"identity":"358a4bb9-06bb-4b41-9eb1-6d7f81b09400","order_by":15,"name":"Ansley Kunnath","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ansley","middleName":"","lastName":"Kunnath","suffix":""},{"id":29775107,"identity":"f3062c93-c271-4537-aeed-6ae528824787","order_by":16,"name":"Alan Storrow","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alan","middleName":"","lastName":"Storrow","suffix":""},{"id":29775108,"identity":"3f898038-798e-4174-aa26-99096a144604","order_by":17,"name":"Charles Seamens","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Charles","middleName":"","lastName":"Seamens","suffix":""},{"id":29775109,"identity":"ef795ca4-4a4b-4e3c-8461-965b4ebdb19d","order_by":18,"name":"Nicole McCoin","email":"","orcid":"","institution":"Ochsner Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nicole","middleName":"","lastName":"McCoin","suffix":""}],"badges":[],"createdAt":"2021-05-19 16:44:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-539457/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-539457/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":9889051,"identity":"de1787ae-d9f8-4e5e-9a2d-092a52fce7c9","added_by":"auto","created_at":"2021-06-02 14:35:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":978634,"visible":true,"origin":"","legend":"Standard 12-lead electrocardiogram demonstrating Seamens’ Sign with precordial QRS complexes overlapping and/or touching. This is best seen with V2 touching/overlapping V3, as well as V4 touching/overlapping V5. ","description":"","filename":"BMCSeamensSignFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-539457/v1/0bfb508d387c7345e96060e4.png"},{"id":13696221,"identity":"5b0329d9-db45-4c6b-8e67-c95b6a967516","added_by":"auto","created_at":"2021-09-17 13:02:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1312661,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-539457/v1/358c17b7-32e6-47c4-af9b-69986ff1f38e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Seamens’ Sign: A Novel Electrocardiogram Prediction Tool for Left Ventricular Hypertrophy","fulltext":[{"header":"1.0 Background","content":" \u003cp\u003ePatients with left ventricular hypertrophy (LVH) diagnosed by electrocardiogram (ECG) have increased mortality and a higher risk for life-threatening cardiovascular disease, most commonly coronary artery disease in men and heart failure in women.\u003ca class=\"FNLink\" href=\"#Fn2\" id=\"#FNLinkFn2\"\u003e\u003c/a\u003e\u003csup\u003e,\u003c/sup\u003e\u003ca class=\"FNLink\" href=\"#Fn3\" id=\"#FNLinkFn3\"\u003e\u003c/a\u003e LVH is commonly diagnosed via ECG in the emergency department (ED), often in cardiac workup or incidentally. These LVH diagnoses provide evidence of patients\u0026rsquo; overall cardiovascular health and inform cardiac risk management and stratification.\u003ca class=\"FNLink\" href=\"#Fn4\" id=\"#FNLinkFn4\"\u003e\u003c/a\u003e\u003c/p\u003e \u003cp\u003eThe process of diagnosing LVH is multi-faceted. Cardiac echocardiography or left ventricular mass measurements via cardiac magnetic resonance imaging (MRI) are the gold standards\u003ca class=\"FNLink\" href=\"#Fn5\" id=\"#FNLinkFn5\"\u003e\u003c/a\u003e\u003csup\u003e,\u003c/sup\u003e\u003ca class=\"FNLink\" href=\"#Fn6\" id=\"#FNLinkFn6\"\u003e\u003c/a\u003e. However, widespread LVH screening via these methods is neither feasible nor cost effective. ECGs performed in the ED setting offer an opportunity to identify patients with increased risk for cardiac mortality and who are candidates for potential risk-modifying therapy. Despite the importance of efficient, accurate LVH prediction based on ECGs, commonly used methods have known diagnostic test inaccuracies and are challenging to use.\u003ca class=\"FNLink\" href=\"#Fn7\" id=\"#FNLinkFn7\"\u003e\u003c/a\u003e\u003c/p\u003e \u003cp\u003eMost current criteria require measuring or adding varying lead voltages, and may be complicated by risk of calculation errors. There are numerous ECG criteria for identifying LVH, with varying tests characteristics influenced by underlying cardiac conduction defects, gender, race, and body habitus.\u003ca class=\"FNLink\" href=\"#Fn8\" id=\"#FNLinkFn8\"\u003e\u003c/a\u003e\u003csup\u003e,\u003c/sup\u003e\u003ca class=\"FNLink\" href=\"#Fn9\" id=\"#FNLinkFn9\"\u003e\u003c/a\u003e\u003csup\u003e,\u003c/sup\u003e\u003ca class=\"FNLink\" href=\"#Fn10\" id=\"#FNLinkFn10\"\u003e\u003c/a\u003e\u003c/p\u003e \u003cp\u003eUltimately, ECG diagnostic criteria for LVH are clinically lacking. Though many attempts at defining more sensitive and specific ECG criteria for LVH have been proposed, none approach the accuracy of gold-standard imaging modalities\u003ca class=\"FNLink\" href=\"#Fn11\" id=\"#FNLinkFn11\"\u003e\u003c/a\u003e. These proposed criteria generally increase complexity to marginally improve sensitivity and/or specificity, creating a barrier to quick application in the ED setting.\u003c/p\u003e \u003cp\u003eInstead of more complex ECG criteria, we propose a novel, quick, and easily recognizable screening criterion for LVH can be learned with little memorization and applied in a fast-paced setting. The proposed criterion\u0026mdash; \u0026ldquo;Seamens\u0026rsquo; Sign\u0026rdquo;\u0026mdash;involves one question: do any of the QRS complexes in the precordial leads of a standard 12-lead ECG touch or cross another QRS complex (e.g., V1 QRS complex touching/crossing V2 QRS complex) (Fig.\u0026nbsp;1)?\u003c/p\u003e \u003cp\u003eFrom an electrophysiologic standpoint, many reasons explain why precordial lead QRS complex touching/overlap works for LVH detection. Typical, non-pathologic R wave progression in the precordial leads shows that as the electrical signal passes from the sinoatrial node towards the apex of the left ventricle, prominent S waves (overall negative deflection) in V1 and V2 transition to predominant R waves (overall positive deflection) in V5 and V6. As the left ventricle hypertrophies, changes occur leading to an electrical vector of greater magnitude, translating to increased amplitude of the S and R waves in the precordial leads, often leading to the precordial QRS complexes touching or overlapping.\u003ca class=\"FNLink\" href=\"#Fn12\" id=\"#FNLinkFn12\"\u003e\u003c/a\u003e\u003csup\u003e,\u003c/sup\u003e\u003ca class=\"FNLink\" href=\"#Fn13\" id=\"#FNLinkFn13\"\u003e\u003c/a\u003e\u003c/p\u003e \u003cp\u003eIn this study, we evaluated the test characteristics of the proposed Seamens\u0026rsquo; Sign and compared its ability to confirm an LVH diagnosis against three of the most used voltage criteria today (two Sokolow-Lyon criteria and the Cornell Criteria).\u003c/p\u003e "},{"header":"2.0 Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eThis study was an electronic health record (EHR) retrospective chart review at a quaternary care academic medical center. The data collection period included clinical tests performed 5 July 2019 through 14 January 2020 as part of routine ED care.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Eligibility\u003c/h2\u003e \u003cp\u003eA query of the EHR was performed, identifying patients with both an ECG and a transthoracic echocardiogram (TTE) performed within 90 days of each other. No patients were excluded prior to data analysis on the basis of age, ethnicity, comorbidities, co-existing cardiac diagnoses evident on ECG or TTE, or other clinical factors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data Collection \u0026amp; ECG Coding\u003c/h2\u003e \u003cp\u003eTotal sample size for chart review was determined based on the number of subjects needed to estimate the sensitivity of Seamens\u0026rsquo; Sign to a pre-specified margin of error. A total of 2184 patient records were reviewed based on estimating a hypothesized sensitivity of 65% to a 2% margin of error. Data gathered during the initial EHR query included age, sex, ECG time/date, and TTE time/date. Each patient chart was assembled by an initial set of reviewers (primarily third year medical students), and assigned a random study number. They downloaded a copy of the ECG labeled with the study number and with all patient identifiers removed. They reviewed the TTE report and recorded whether or not LVH was identified. LVH was defined as any mention of the patient having concentric LVH in the TTE report. Septal or other focal hypertrophy was not considered LVH.\u003c/p\u003e \u003cp\u003e A second, independent set of blinded reviewers (Emergency Medicine residents) reviewed each ECG for signs of LVH based on two Sokolow-Lyon criteria, the Cornell criteria, and the study criterion, Seamens\u0026rsquo; Sign. The first criterion, noted as the Sokolow-Lyon 1 criterion (SL-1) was defined as the S wave in lead V1 plus the R wave in lead V5 or V6 (using larger R wave in V5 or V6) being greater than or equal to 35mm. The second Sokolow-Lyon criterion, noted as Sokolow-Lyon 2 criterion (SL-2), was defined as the R wave in lead aVL being greater than or equal to 11mm. The Cornell criteria were defined as the S wave in lead V3 plus the R wave in lead aVL being greater than 28mm in males or greater than 20mm in females. These criteria\u0026rsquo;s test characteristics were compared against the test characteristics for the proposed new criterion, Seamens\u0026rsquo; Sign. This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads (lead V1 QRS complex touching/crossing lead V2 QRS complex, or lead V2 QRS complex touching/crossing lead V3 QRS complex, or lead V4 QRS complex touching/crossing lead V5 QRS complex, or lead V5 QRS complex touching/crossing lead V6 QRS complex).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOutcome Measures\u003c/span\u003e\u003c/h2\u003e \u003cp\u003eThe primary outcome was determining whether Seamens\u0026rsquo; Sign was noninferior in confirming LVH compared to the other criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAnalysis\u003c/span\u003e\u003c/h2\u003e \u003cp\u003eDiagnosis of concentric LVH by TTE was considered the gold standard against which the various ECG criteria for LVH were compared to determine sensitivity and specificity.\u003c/p\u003e \u003cp\u003eDescriptive statistics of demographic and clinical characteristics were computed for the study population. Test characteristics, including sensitivity, specificity, and positive and negative predictive values, along with their 95% confidence intervals, were calculated for each of the LVH criteria. Non-inferiority of Seamens\u0026rsquo; Sign criterion compared to the Cornell and Sokolow-Lyon criteria was evaluated using a method designed for paired binary data.\u003ca class=\"FNLink\" href=\"#Fn14\" id=\"#FNLinkFn14\"\u003e\u003c/a\u003e The margin of non-inferiority was pre-specified at 5% (p\u0026thinsp;=\u0026thinsp;0.05). To compare Cornell criteria for men and women to those with Seamens\u0026rsquo; Sign, only men with Seamens\u0026rsquo; Sign were compared to other men meeting Cornell criteria, and the same method was used for women. To ensure validity of reviewer ECG coding and assess ease of interpretation, inter-rater agreement was assessed on a random sample using Cohen\u0026rsquo;s Kappa with the 95% confidence intervals. All statistical analyses were performed using R statistical programming language, Version 3.5.2.\u003c/p\u003e \u003c/div\u003e "},{"header":"3.0 Results","content":" \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePatient Characteristics\u003c/span\u003e\u003c/h2\u003e \u003cp\u003ePatient characteristics are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by TTE. The vast majority of TTEs were performed within 1 day of ECGs, with the median of 1 day, and the interquartile range of 0 to 21 days. Nine percent were positive for LVH on ECG based on Seamens\u0026rsquo; Sign, and 3% and 7% were positive for LVH on ECG based on Sokolow-Lyon 1 and Sokolow-Lyon 2 criteria, respectively. There were 7% of men and 13% of women positive for LVH on ECG based on Cornell criteria.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescriptive statistics on demographic and clinical characteristics of the cohort. N is the number of non-missing values. Numbers after proportions are frequencies, with the exception of age and ECG to TTE. Age and ECG to TTE are reported as the median, with following numbers the lower and upper interquartile for these continuous variables.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;2184\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (51, 73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52% (1135)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48% (1049)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTTE for LVH (gold standard)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65% (1428)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35% (756)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eECG to TTE (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0, 21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSeamens' Sign positive for LVH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91% (1994)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9% (190)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSokolow-Lyon 1 positive for LVH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97% (2113)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3% (71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSokolow-Lyon 2 positive for LVH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93% (2037)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7% (147)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCornell (overall) positive for LVH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90% (1971)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10% (213)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCornell (men) positive for LVH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93% (1056)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7% (79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCornell (women) positive for LVH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87% (914)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13% (135)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Sensitivity and Specificity\u003c/h2\u003e \u003cp\u003eTest characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Specificities ranged from 0.89 for the Cornell criterion for women to 0.98 for the Sokolow-Lyon 1 criterion, with Seamens\u0026rsquo; Sign having a specificity of 0.92.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTest characteristics for Seamens\u0026rsquo; Sign criterion, Sokolow-Lyon 1 (SL-1) and 2 (SL-2) criteria, and Cornell criteria for diagnosing left ventricular hypertrophy from electrocardiograms.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003ePPV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eNPV\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEstimate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eEstimate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eEstimate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eEstimate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeamens' Sign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.09, 0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.91, 0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.36, 0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(0.64, 0.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSL-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.03, 0.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.97, 0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.39, 0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(0.64, 0.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSL-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.06, 0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.93, 0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.33, 0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(0.64, 0.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Overall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.11, 0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.90, 0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.39, 0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(0.64, 0.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Men\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.07, 0.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.92, 0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.39, 0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(0.59, 0.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Women\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.14, 0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.87, 0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.34, 0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(0.68, 0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Non-Inferiority\u003c/h2\u003e \u003cp\u003eTests assessing noninferiority indicated Seamens\u0026rsquo; Sign was non-inferior to all criteria (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) except for Cornell criterion for women (p\u0026thinsp;=\u0026thinsp;0.98) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ep-values for tests assessing non-inferiority of Seamens\u0026rsquo; Sign when compared to other commonly used tests.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComparison\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSokolow-Lyon 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSokolow-Lyon 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Overall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Men\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Women\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Inter-Rater Agreement\u003c/h2\u003e \u003cp\u003eInter-rater agreement was assessed on 250 subjects using Cohen\u0026rsquo;s Kappa statistic and a 95% confidence interval (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Seamens\u0026rsquo; Sign had 90% (0.81-1.00) agreement, the highest of all criteria, attributed to its quick application and ease of use. Sokolow-Lyon 1 and Sokolow-Lyon 2 had inter-rater agreement of 65% (0.40\u0026ndash;0.91) and 87% (0.75-1.00) respectively. Sokolow-Lyon 1 likely has lower inter-rater agreement secondary to multiple leads used and subjectivity in selecting the R wave in lead V5 or V6. Cornell criteria for men and women had inter-rater agreements of 76% (0.56\u0026ndash;0.96) and 79% (0.62\u0026ndash;0.97), respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInter-rater agreement using Cohen\u0026rsquo;s Kappa with 95% confidence interval.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKappa\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeamens' Sign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.81, 1.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSokolow-Lyon 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.40, 0.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSokolow-Lyon 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.75, 1.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell Overall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.69, 0.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell (Men)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.56, 0.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCornell (Women)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.62, 0.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"4.0 Discussion","content":" \u003cp\u003eWhile modalities other than ECG are the gold-standard for diagnosing LVH, it is important to account for their difficulty and cost compared to the quick, easy to obtain, and inexpensive ECG, particularly in emergency care settings. Furthermore, there are data suggesting LVH diagnosed by ECG criteria represents a clinically distinct entity, and has been associated with increased mortality and other pathologic conditions.\u003ca class=\"FNLink\" href=\"#Fn15\" id=\"#FNLinkFn15\"\u003e\u003c/a\u003e This furthers the argument of the importance of fast, reliable methods of diagnosing LVH by ECG.\u003c/p\u003e \u003cp\u003eThis analysis suggests Seamens\u0026rsquo; Sign is non-inferior to other methods of evaluating LVH on ECG, and has high inter-rater agreement. It is easy to perform quickly without a measurement device or need for any calculations at all. Given these findings, we believe that Seamens\u0026rsquo; Sign is easily applicable in emergency care settings and can facilitate the diagnosis of LVH, potentially leading to decreased cardiac morbidity and mortality.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Strengths\u003c/h2\u003e \u003cp\u003eThis is a large study comparing test characteristics of multiple criteria to Seamens' Sign.\u003c/p\u003e \u003cp\u003eThree of the most widely used criteria were chosen to model real-world application. Compared to most prior studies, the number of subjects analyzed was larger. Of the prior 14 studies analyzing ECG diagnosis of LVH, enrollment ranged from 94 to 5608 patients; this study is the third largest. Those interpreting ECGs were blinded from the TTE results to remove any bias. The proliferative phase of cardiac remodeling takes place within the first 2\u0026ndash;7 days after a myocardial infarction, transitioning to the maturing phase around day 7.\u003ca class=\"FNLink\" href=\"#Fn16\" id=\"#FNLinkFn16\"\u003e\u003c/a\u003e Based on these findings, a 90-day limit on the time difference between the TTE and ECG dates was placed to reduce the likelihood of cardiac remodeling affecting results. The majority of the ECGs and TTEs were performed within 1 day of each other, limiting the chances of cardiac remodeling affecting the ECG or TTE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Limitations\u003c/h2\u003e \u003cp\u003eWhile Seamens\u0026rsquo; Sign is a quick, effective, reliable alternative to other criteria for diagnosing LVH on ECG, there are study limitations. All ECGs were included, without removal of bundle branch blocks or other abnormal findings that could alter the results. However, this limitation was applied across all criteria in the study, helping to eliminate any differences in their application. Also, with the exception of the Cornell criteria which differentiates between sexes, we did not differentiate the application of the other criteria based on sex. This could hide differences in application of the criteria between sexes, but stays true to original application of these criteria. There were no changes in application of criteria based on age. There are known differences in ECG appearance based on age, including potential QRS amplitude changes.\u003ca class=\"FNLink\" href=\"#Fn17\" id=\"#FNLinkFn17\"\u003e\u003c/a\u003e Finally, since this was a retrospective study, there were multiple providers obtaining ECGs, multiple echocardiographers performing the TTEs, and multiple cardiologists reading the TTEs, which could lead to variability in ECG and TTE acquisition, interpretation, and reporting of LVH.\u003c/p\u003e \u003c/div\u003e "},{"header":"5.0 Conclusion","content":" \u003cp\u003eWhen compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens\u0026rsquo; Sign is noninferior in confirming LVH on ECG. Additionally, Seamens\u0026rsquo; Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, possibly related to its ease of use.\u003c/p\u003e "},{"header":"6.0 Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.1 Ethics approval and consent to participate\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study (IRB#200150) was approved by the Vanderbilt Institutional Review Board and Human Research Protections Program as an exempt study that poses minimal risk to participants given it only involved retrospective chart review. The informed consent for this study is waived by the Vanderbilt Institutional Review Board due to retrospective nature. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.2 Consent for publication\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe informed consent for this study is waived by the Vanderbilt Institutional Review Board due to retrospective nature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.3 Availability of data and materials\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due being secured in a private, password protected, Vanderbilt University Medical Center (VUMC) repository only available to VUMC employees, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.4 Competing interests\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.5 Funding\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no internal or external funding for this research study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.6 Authors' contributions\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePWW, NM, ABS, CAJ, and CS conceived and designed the study. PWW, NM, and ABS were responsible for drafting and obtaining IRB approval. PWW and NM supervised data collection and conduction of the study. CAJ provided statistical advice on study design and analyzed the data. JBS, EH, CM, TR, LCW, TP, RP, AA, OH, JO, and AK were the primary initial chart reviewers. CLF, NS, and BR were the second set of blinded reviewers. PWW drafted the manuscript, and all authors contributed substantially to its revision. PWW takes responsibility for the paper as a whole.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e6.7 Acknowledgements\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"7.0 List Of Abbreviations","content":"\u003cp\u003eECG\u0026mdash;Electrocardiogram\u003c/p\u003e\n\u003cp\u003eED\u0026mdash;Emergency department\u003c/p\u003e\n\u003cp\u003eEHR\u0026mdash;Electronic health record\u003c/p\u003e\n\u003cp\u003eLVH\u0026mdash;Left ventricular hypertrophy\u003c/p\u003e\n\u003cp\u003eMRI\u0026mdash;Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eNPV\u0026mdash;Negative predictive value\u003c/p\u003e\n\u003cp\u003ePPV\u0026mdash;Positive predictive value\u003c/p\u003e\n\u003cp\u003eSL-1\u0026mdash;Sokolow-Lyon 1 criterion\u003c/p\u003e\n\u003cp\u003eSL-2\u0026mdash;Sokolow-Lyon 2 criterion\u003c/p\u003e\n\u003cp\u003eTTE\u0026mdash;Transthoracic echocardiogram\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSundstr\u0026ouml;m J, Lind L, Arnl\u0026ouml;v J, Zethelius B, Andr\u0026eacute;n B, Lithell HO. Echocardiographic and electrocardiographic diagnoses of left ventricular hypertrophy predict mortality independently of each other in a population of elderly men. Circulation. 2001;103(19):2346-51.\u003c/li\u003e\n\u003cli\u003eDesai CS, Ning H, Lloyd-jones DM. Competing cardiovascular outcomes associated with electrocardiographic left ventricular hypertrophy: the Atherosclerosis Risk in Communities Study. Heart. 2012;98(4):330-4.\u003c/li\u003e\n\u003cli\u003eBacharova L, Estes EH. Left Ventricular Hypertrophy by the Surface ECG. J Electrocardiol. 2017;50(6):906-908.\u003c/li\u003e\n\u003cli\u003eLang RM, Badano LP, Mor-avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14.\u003c/li\u003e\n\u003cli\u003eZhang W, Zhou Y, Bai B, et al. Consistency of left ventricular hypertrophy diagnosed by electrocardiography and echocardiography: the Northern Shanghai Study. Clin Interv Aging. 2019;14:549-556.\u003c/li\u003e\n\u003cli\u003eHedman K, Moneghetti KJ, Hsu D, et al. Limitations of Electrocardiography for Detecting Left Ventricular Hypertrophy or Concentric Remodeling in Athletes. Am J Med. 2020;133(1):123-132.e8.\u003c/li\u003e\n\u003cli\u003eAntikainen RL, Grodzicki T, Palmer AJ, et al. Left ventricular hypertrophy determined by Sokolow-Lyon criteria: a different predictor in women than in men?. J Hum Hypertens. 2006;20(6):451-9.\u003c/li\u003e\n\u003cli\u003eJaggy C, Perret F, Bovet P, et al. Performance of classic electrocardiographic criteria for left ventricular hypertrophy in an African population. Hypertension. 2000;36(1):54-61.\u003c/li\u003e\n\u003cli\u003eGermano G. Electrocardiographic signs of left ventricular hypertrophy in obese patients: what criteria should be used?. High Blood Press Cardiovasc Prev. 2015;22(1):5-9.\u003c/li\u003e\n\u003cli\u003eMahn JJ, Dubey E, Brody A, et al. Test characteristics of electrocardiography for detection of left ventricular hypertrophy in asymptomatic emergency department patients with hypertension. Acad Emerg Med. 2014;21(9):996-1002.\u003c/li\u003e\n\u003cli\u003eHill JA. Hypertrophic reprogramming of the left ventricle: translation to the ECG.\u0026nbsp;J Electrocardiol. 2012;45(6):624-629.\u003c/li\u003e\n\u003cli\u003eBacharova L, Szathmary V, Kovalcik M, Mateasik A. Effect of changes in left ventricular anatomy and conduction velocity on the QRS voltage and morphology in left ventricular hypertrophy: a model study.\u0026nbsp;J Electrocardiol. 2010;43(3):200-208.\u003c/li\u003e\n\u003cli\u003eLiu JP, Hsueh HM, Hsieh E, Chen JJ. Tests for equivalence or non-inferiority for paired binary data. Stat Med. 2002;21(2):231-45.\u003c/li\u003e\n\u003cli\u003eAro AL, Chugh SS. Clinical diagnosis of electrical versus anatomic left ventricular hypertrophy: prognostic and therapeutic implications.\u0026nbsp;Circ Arrhythm Electrophysiol. 2016;9(4):e003629.\u003c/li\u003e\n\u003cli\u003eFrench BA, Kramer CM. Mechanisms of post-infarct left ventricular remodeling.\u0026nbsp;Drug Discov Today Dis Mech. 2007;4(3):185-196.\u003c/li\u003e\n\u003cli\u003eLevy D, Bailey JJ, Garrison RJ, et al. Electrocardiographic changes with advancing age. A cross-sectional study of the association of age with QRS axis, duration and voltage.\u0026nbsp;J Electrocardiol. 1987;20 Suppl:44-47.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Electrocardiogram, electrocardiography, left ventricular hypertrophy, emergency medicine","lastPublishedDoi":"10.21203/rs.3.rs-539457/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-539457/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eStudy Objective:\u003c/h2\u003e \u003cp\u003eWe developed a novel, quick, easy to use electrocardiogram (ECG) screening criterion (Seamens\u0026rsquo; Sign) for left ventricular hypertrophy (LVH). This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eThis study was a retrospective chart review of 2184 patient records. The primary outcome was whether Seamens\u0026rsquo; Sign was noninferior in confirming LVH compared to other common criteria. Test characteristics were calculated for each of the LVH criteria. Inter-rater agreement was assessed on a random sample using Cohen\u0026rsquo;s Kappa.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eMedian age was 63, 52% of patients were male and there was a 35% prevalence of LVH by transthoracic echocardiogram (TTE). Nine percent were positive for LVH on ECG based on Seamens\u0026rsquo; Sign. Seamens\u0026rsquo; Sign had a specificity of 0.92. Tests assessing noninferiority indicated Seamens\u0026rsquo; Sign was non-inferior to all criteria (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) except for Cornell criterion for women (p\u0026thinsp;=\u0026thinsp;0.98). Seamens\u0026rsquo; Sign had 90% (0.81-1.00) inter-rater agreement, the highest of all criteria in this study.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eWhen compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens\u0026rsquo; Sign is noninferior in ruling in LVH on ECG. Additionally, Seamens\u0026rsquo; Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, perhaps related to its ease of use.\u003c/p\u003e","manuscriptTitle":"Seamens’ Sign: A Novel Electrocardiogram Prediction Tool for Left Ventricular Hypertrophy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-06-02 14:35:40","doi":"10.21203/rs.3.rs-539457/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fde0d80b-688b-47e7-9317-e0cad67a793b","owner":[],"postedDate":"June 2nd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":4682946,"name":"Critical Care \u0026 Emergency Medicine"},{"id":4682947,"name":"Biostatistics"},{"id":4682948,"name":"General Surgery"}],"tags":[],"updatedAt":"2021-09-09T02:59:07+00:00","versionOfRecord":[],"versionCreatedAt":"2021-06-02 14:35:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-539457","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-539457","identity":"rs-539457","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}