Can Junior EPs Use E-Point Septal Separation to Accurately Estimate Left Ventricular Function?

Background

Point-of-care echocardiography can provide a rapid and accurate assessment of left ventricular function, which is valuable in differentiating causes of hypotension and dyspnea at bedside. Visual estimation of LV function by experienced practitioners has been shown to correlate well with quantitative estimates. However, the number of examinations required before a practitioner is qualified to visually estimate LV function accurately is unknown. Although there are various comparable parameters for assessing LV function, mitral valve E-point septal separation (EPSS) is an easy-to-obtain measurement inversely correlated with LV function. EPSS is an M-mode measurement of the minimum distance between the anterior mitral valve leaflet and the interventricular septum during diastole. Despite its applicability, the reproducibility and accuracy of EPSS as a bedside tool for evaluating LV function in less experienced emergency physicians has yet to be established.

Can Junior Emergency Physicians Use E-Point Septal Separation to Accurately Estimate Left Ventricular Function in Acutely Dyspneic Patients? 

Clinical Question

This study aims to determine if novice emergency physicians (PGY 3 and PGY 4) are able to obtain EPSS measurements and determine if these measurements correlate to echocardiographic visual estimations of LV function by experienced emergency physicians.

Methods & Study Design

Design:
Prospective observational study of correlation between EPSS to visual estimation and LV function in patients who present to ED with chief complaint of acute dyspnea.

Population:
Convenience sampling of 70 subjects enrolled in the ED from July 2008 and July 2009. Criteria for enrollment included age > 18 years, chief complaint of dyspnea, ED length > 2 hours, no history of trauma, and normal mental status. Patients with known history of mitral valve repair or replacement, aortic insufficiency, or mitral stenosis were excluded.

Intervention:
12 senior residents (PGY 3 and PGY 4) in EM residency program with variable levels of ultrasound experiences (70 to 150 total ED ultrasound examinations; average of fewer than 25 cardiac examinations) performed transthoracic echocardiogram of patients with chief complaint of acute dyspnea. Ultrasound examination included subcostal, parasternal long axis (PLAX), parasternal short axis, and apical four chamber views. Six-second video clips in parasternal short and long axes were obtained. M-mode measurements of EPSS were recorded in PLAX orientation after all video clips were obtained and calculated during diastole. All examinations were performed without the presence of experienced emergency physicians (EPs).

Outcomes:
One of two experienced EPs reviewed stored video and visually estimated LVEF. Two board-certified cardiologists subsequently reviewed one-half of the video clips and estimated LVEF, blinded to both junior EPs’ EPSS measurements and visual estimations by experienced EPs.

Results

58 out of 70 enrolled subjects had complete echocardiographic studies recorded.

Concordance rates between EPSS measurements by EPs and cardiologist for LVEF were acceptable with kappa for visual LVEF estimation of 0.75 (95% CI = 0.48 to 1.00).

Spearman correlation analysis revealed significant correlation (p = -0.844, p< 0.001) between novice physicians’ measurements of EPSS and visual estimation of LVEF by experienced EPs.

Strengths and Limitations

This study compared EPSS measurement by junior EPs with visual assessment by experienced EPs showing a strong correlation. Experienced EPs were not blinded to results, which may have induced bias, but the authors find this less likely given what they interpret as good agreement on visual estimations between experienced EPs and blinded cardiologists. It is debatable whether the agreement between EPs and cardiologists with kappa of 0.75 represents good agreement. This study utilized a convenience sampling design due to logistical constraints, which may impact the generalizability of its results. Many subjects were excluded for incomplete ultrasound views, but authors note that junior EPs were actually able to assess EPSS for all subjects, further supporting the use of this measurement even when other views are difficult to obtain.

Authors Conclusions

PGY 3 and PGY 4 EM residents were able to obtain measurements of EPSS that correlated closely with visual assessments of LVEF by experienced emergency physicians with extensive point-of-care ultrasound and echocardiography experience. EPSS can serve as a quantitative alternative to visual estimation of LVEF in dyspneic ED patients.

Our Conclusions

Rapid assessment of LVEF with bedside echocardiography can provide useful clinical information in the acutely dyspneic patient. The level of expertise required to accurately visually assess a LVEF is unknown. This study supports EPSS as a useful quantitative addition to visual estimation of LVEF in patients with acute dyspnea for novice emergency physicians with less echocardiography experience. The level of correlation between EPSS and visual estimation was not perfect, suggesting use of EPSS as an addition to rather than replacement for standard visual estimation.

The Bottom Line 

EPSS can serve as a quantitative addition to qualitative visual estimation of LVEF with bedside echocardiography, especially for less experienced EM practitioners.

Authors

This post was written by Eugene Han, MS4 at UCSD School of Medicine, with editing by Ben Liotta, MD and Amir Aminlari, MD. 

References

1. Secko MA, Lazar JM, Salciccioli LA, Stone MB. Can junior emergency physicians use E-point septal separation to accurately estimate left ventricular function in acutely dyspneic patients? Acad Emerg Med. 2011 Nov;18(11):1223-6. doi: 10.1111/j.1553-2712.2011.01196.x. Epub 2011 Nov 1. PMID: 22044429.
2. McKaigney CJ, Krantz MJ, La Rocque CL, Hurst ND, Buchanan MS, Kendall JL. E-point septal separation: a bedside tool for emergency physician assessment of left ventricular ejection fraction. Am J Emerg Med. 2014 Jun;32(6):493-7. doi: 10.1016/j.ajem.2014.01.045. Epub 2014 Feb 3. PMID: 24630604.
3. Shahgaldi K, Gudmundsson P, Manouras A, Brodin LA, Winter R. Visually estimated ejection fraction by two dimensional and triplane echocardiography is closely correlated with quantitative ejection fraction by real-time three dimensional echocardiography. Cardiovasc Ultrasound. 2009 Aug 25;7:41. doi: 10.1186/1476-7120-7-41. PMID: 19706183; PMCID: PMC2747837.
4. McGowan JH, Cleland JG. Reliability of reporting left ventricular systolic function by echocardiography: a systematic review of 3 methods. Am Heart J. 2003 Sep;146(3):388-97. doi: 10.1016/S0002-8703(03)00248-5. PMID: 12947354.
5. Jacob M, Shokoohi H, Moideen F, Pousson A, Boniface K. An Echocardiography Training Program for Improving the Left Ventricular Function Interpretation in Emergency Department; a Brief Report. Emerg (Tehran). 2017;5(1):e70. Epub 2017 Jun 15. PMID: 29201952; PMCID: PMC5703747.

Can ED physicians use TAPSE to rule out PE?

tapse ultrasound

Background

Pulmonary embolism (PE) often makes it on the differential of emergency department (ED) patients with any sort of cardiac or pulmonary complaint, and it can be a diagnostic challenge to know how far into the work up of PE is necessary for each patient. Any bedside tool that can increase or decrease the likelihood ratio for PE could be beneficial. Bedside echocardiography is one of the key tools in an ED physicians belt to narrow down differentials or potentially rule out certain diseases.

Research shows that 30 to 70% of emergency department patients with a PE will exhibit signs of right ventricular dysfunction (RVD), and a focused transthoracic cardiac ultrasound (FOCUS) is effective at detecting RVD (1). However, common measures of RVD, such as right heart enlargement, can be challenging to assess and often are dependent on the operator (2,3). A different measure, tricuspid annular plane systolic excursion (TAPSE), has been shown to accurately detect RVD while also providing prognostic information and is the least user dependent measure (4-9).

To date, there is little research on the utility of TAPSE in diagnosing PE, this study aimed to assess the diagnostic characteristics of TAPSE for PE and to optimize the measurement cutoff of TAPSE in diagnosing a PE.

 

Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism

 

Clinical Question

    • How accurate is TAPSE in diagnosing a PE?
    • What is the optimal measurement cutoff of TAPSE in diagnosing a PE ?
    • How good is the inter-rater reliability of TAPSE
    • How good are physicians at visually estimating TAPSE?

Methods & Study Design

• Design 

Prospective, observational convenience sample of FOCUS in ED patients undergoing evaluation for suspected PE from April 2015 to April 2016.

• Population 

Subjects were eligible if they were 18 years or older and undergoing computed tomographic angiography (CTA) for evaluation of possible PE in the ED. Prisoners, wards of the state, and non–English-speaking patients were excluded.

• Intervention 

Patients underwent a FOCUS in the ED either prior to undergoing CTA or the operator was blinded to the results if the FOCUS was done after the CTA. The operators were ultrasound trained emergency physicians, fellow,  or residents with one medical student participating who was trained in measuring TAPSE.

• Outcomes  

The primary outcome was both describing the diagnostic test characteristics of TAPSE in diagnosing PE and optimizing the measurement cutoff of TAPSE in diagnosing a PE. The secondary outcomes were assessing inter-rater reliability, quantitative visual estimate of TAPSE, and to describe the diagnostic test characteristics of other measures of RVD.

Results

The study found that TAPSE was 72% sensitive and 66% specific when the cutoff was 2.0 cm. When using the pre-established TAPSE cut off of 1.7, TAPSE was 56% sensitive and 79% specific.

They noted that in the sub-group of patients who were either tachycardic or hypotensive, TAPSE became 94% specific and the FOCUS was 100% specific.

Additionally, TAPSE had high inter-rater reliability, physicians were able to qualitatively assess TAPSE as normal or abnormal, and the test characteristics of TAPSE were much more sensitive and specific for a PE than other measures on the FOCUS.

Strength & Limitations

Strengths:

This study was well designed for the question it sought to answer and did a good job limiting bias by blinding the participants. They asked clinically relevant questions.

Limitations:

This study was limited in that it was a convenience sample of patients making it susceptible to selection bias. Additionally, the ultrasound operators in this study had extensive ultrasound training and TAPSE training, thus it may not be generalizable to the standard population of emergency physicians.

Authors Conclusion

"The optimal cutoff for diagnosis of PE using TAPSE was determined to be 2.0 cm. The diagnostic test characteristics of TAPSE for PE are comparable to other measures of RVD, although TAPSE appears to be somewhat more sensitive and less specific. The incorporation of TAPSE into the evaluation of the right heart may increase the accuracy and reliability of beside echocardiography for the detection of PE, although our data suggest that FOCUS is of limited utility in all patients presenting with concern for PE.

However, FOCUS and TAPSE appear to be highly sensitive for PE in patients with tachycardia or hypotension. Additionally, emergency physicians with advanced training in emergency ultrasound are capable of measuring TAPSE with precision comparable to that reported in the cardiology literature. Emergency physicians are able to accurately visually estimate TAPSE as either normal or abnormal, based on an a prior cutoff of 1.7 cm. As a more reliable measure of RVD, TAPSE may also help EPs to determine the severity and prognosis of a patient diagnosed as having a PE."

Our Conclusion

TAPSE is only a moderately sensitive and specific test in diagnosing a PE. However, TAPSE can be a useful tool in patients who are hemodynamically unstable with a suspected PE. In this case, the sensitivity of TAPSE in diagnosing a PE increases dramatically and in the setting of a hemodynamically unstable patient with a normal TAPSE, PE is unlikely the etiology. This can be beneficial if a patient is too unstable to go for a CTA, to help with diagnostic clarification and decision making.

The Bottom Line 

TAPSE is not sensitive or specific enough to rule in or rule out PE, but the sensitivity dramatically improves in hemodynamically unstable patients. TAPSE has high inter-rater reliability.

Authors

This post was written by Allie Frankel, MS4 at UCSD School of Medicine, Charles Murchison, MD and Amir Aminlari, MD. 

References

Daley J, Grotberg J, Pare J, Medoro A, Liu R, Hall MK, Taylor A, Moore CL. Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism. Am J Emerg Med. 2017 Jan;35(1):106-111. doi: 10.1016/j.ajem.2016.10.018. Epub 2016 Oct 11. PMID: 27793505.

 

    1. Matthews JC, Mclaughlin V. Acute Right Ventricular Failure in the Setting of Acute Pulmonary Embolism or Chronic Pulmonary Hypertension: A Detailed Review of the Pathophysiology, Diagnosis, and Management. Curr Cardiol Rev 2008;4:49–59.

    2. Pruszczyk P, Goliszek S, Lichodziejewska B, Kostrubiec M, Kurnicka K, Dzikowska- Diduch O, et al. Prognostic value of echocardiography in normotensive patients with acute pulmonary embolism. JACC Cardiovasc Imaging 2014;7(6):553–60.

    3. Zanobetti M, Converti C, Conti A, Viviani G, Guerriniti E, Boni V, et al. Prognostic Value of Emergency Physician Performed Echcardiography in Patients with Acute Pulmonary Embolism. West J Emerg Med 2013;14(5):509–17.

    4. Kline JA, Steuerwald MT, Marchick MR, Hernandez-Nino J, Rose GA. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009;136(5):1202–10.

    5. Jackson RE, Rudoni RR, Hauser AM, Pascual RG, Hussey ME. Prospective evaluation of two-dimensional transthoracic echocardiography in emergency department pa- tients with suspected pulmonary embolism. Acad Emerg Med 2000;7(9):994–8.

    6. Rudoni RR, Jackson RE, Godfrey GW, Bonfiglio AX, Hussey ME, Hauser AM. Use of Two-Dimensional Echocardiography for the Diagnosis of Pulmonary Embolus. J Emerg Med 1998;16(1):5–8.

    7. Bova C, Greco F, Misuraca G, Serafini O, Crocco F, Greco A, et al. Diagnostic utility of echocardiography in patients with suspected pulmonary embolism. Am J Emerg Med 2003;21(3):180–3.

    8. Kopecna D, Briongos S, Castillo H, Moreno C, Recio M, Navas P, et al. Interobserver reliability of echocardiography for prognostication of normotensive patients with pulmonary embolism. Cardiovasc Ultrasound 2014;12:29–38.

    9. Taylor RA, Moore CL. Accuracy of emergency physician-performed limited echocar- diography for right ventricular strain. Am J Emerg Med 2014;32(4):371–4. 

Identifying regional wall motion abnormalities on ultrasound

regional wall motion abnormalities

Background

Traditionally, the focus of emergency point-of-care echocardiography has been threefold: to assess left ventricular systolic function, to identify the presence of right ventricular enlargement and to evaluate for pericardial effusion. Assessing for regional wall motion abnormalities has been left to formal echocardiography and Cardiology (1). However, structural abnormalities can appear within seconds from the onset of myocardial ischemia (2), so identifying wall motion abnormalities in patients with chest pain or suspected acute coronary syndrome (ACS) in the Emergency Department may be clinically beneficial for emergency providers, leading to more prompt and appropriate diagnostic or therapeutic measures.

We evaluate the following article that looks at whether ED physicians can accurately identify regional wall motion abnormalities.

WAMAMI: emergency physicians can accurately identify wall motion abnormalities in acute myocardial infarction

 
 

Clinical Question

Can emergency physicians with basic training in emergency echocardiography accurately identify regional wall motion abnormalities (RWMA) in patients admitted with STEMI?

Methods & Study Design

• Design 

Observational report – one group of residents trained and tested in an ultrasound procedure.

• Population 

75 patients admitted with STEMI. 6 were excluded from the analysis due to withdrawal, leaving AMA or inability to obtain interpretable images.

• Intervention 

Nine residents viewed 2 video instructional modules to provide an introduction to identifying RWMA, and completed an online test evaluating echocardiographic clips for RWMA. They then performed a bedside echocardiogram on patients with known STEMI, though they were blinded to any clinical data about the patient, including the EKG. This was performed within 24 hours of the formal comprehensive echocardiogram.

• Outcomes  

The primary outcome was agreement between resident performed echo and formal comprehensive echo on the presence and localization of RWMA. 

Results

62% of subjects enrolled had a wall motion abnormality identified by the reference standard. Study investigators identified the presence of RWMA with good sensitivity and specificity (Table 2).

 

Inter-rater agreement between the point-of-care echocardiogram and the formal echocardiogram for the presence of RWMA was K = 0.79 (95% CI: 0.64–0.94).

 

Strength & Limitations

Strengths:

Promising results suggest that emergency medicine physicians can be taught to accurately identify RWMA in STEMI with little training. Though the patients in this study were already known to have STEMI on EKG, the application of this procedure may be helpful when patients arrive with NSTEMI or elevated cardiac markers to help in the clinical decision making.

Limitations:

Study was conducted using just 9 residents, and 2 of the residents did the vast majority of the scans. It is possible that these residents are already skilled in ultrasound, so to truly gauge whether this method is broadly teachable, many more residents (with varying levels of baseline ultrasound experience) would need to be evaluated.

Authors Conclusion

The ability to diagnose a RWMA offers emergency clinicians another tool to help manage patients with chest pain and suspected ACS. These data support the introduction of focused training in RWMA identification and expansion of the clinical use of emergency and critical care echocardiography.

Our Conclusion

This is an interesting concept that emergency medicine residents can be trained to successfully identify RWMA using echocardiography. If, and how, this should be implemented in clinical practice is still yet to be explored. Perhaps this could be used in cases of NSTEMI or elevated cardiac markers to help inform clinical decision making, but this study does not answer the question of whether this skill will be clinically useful for ED physicians. 

The Bottom Line 

It is possible to train emergency medicine physicians to identify regional wall motion abnormalities using echocardiography.

Authors

This post was written by Allison Auchter, MS4 at UCSD School of Medicine, Charles Murchison, MD and Amir Aminlari, MD. 

References

P.E. Croft, T.D. Strout, R.M. Kring, et al., WAMAMI: emergency physicians can accurately identify wall motion abnormalities in acute myocardial infarction, American Journal of Emergency Medicine.

 

    1. Cheitlin MD, Armstrong WF, Aurigemma GP, et al. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines of the Clinical Application of Echocardiography). Circulation 2003;108(9):1146–62.

    2. Wholgelernter D, Cleman M, Highman HA, et al. Regional myocardial dysfunction during coronary angioplasty: evaluation by two-dimensional echocardiography and 12 lead electrocardiography. J Am Coll Cardiol 1986;7(6):1245.

How accurate is EPSS in estimating ejection fraction?

epss echo

Background

Bedside echocardiography has an established role in the time-sensitive assessment for pericardial effusion, relative chamber size, and global cardiac function of emergency department (ED) patients. Most ED physicians use visual estimation to gauge left ventricular ejection fraction (LVEF), a method that may be subject to inter-observer variability and inaccuracy (1). E-point septal separation (EPSS), the minimum separation between the anterior mitral valve leaflet and the interventricular septum, may offer a more objective measure of LVEF.

epss echo

EPSS was first studied in the 1970s as a quantitative, easily measured, and reproducible index of left ventricular function (2). In healthy individuals, the mitral valve leaflet reaches its maximum excursion near or at the septum during early diastole. EPSS increases as left ventricular ejection fraction (LVEF) decreases, and an EPSS of greater than 7mm predicts poor LVEF (3,4).

The gold standard for evaluating LVEF is a quantitative, calculated value obtained from comprehensive transthoracic echocardiography, which is impractical in the emergency department, thus EPSS offers a simple to learn and easy to obtain alternative, requiring only one view in the parasternal long axis. EPSS measurement is a technique feasible for the ED physician to perform at the bedside that can provide a convenient and reliable estimate of LVEF. 

 

E-point septal separation: a bedside tool for emergency physician assessment of left ventricular ejection fraction

Clinical Question

Does EPSS measurements obtained by ED physicians correlate with calculated LVEF from comprehensive transthoracic echocardiography (TTE)?

Can certain EPSS cutoff values be used to predict systolic dysfunction? 

What is the relationship between bedside visual estimates of global cardiac function (GCF) and the calculated LVEF measurements?

Methods & Study Design

• Design 

This was a prospective observational trial.

• Population 

A convenience sample of 80 hospitalized patients undergoing comprehensive TTE for any indication. Subjects were recruited between February and April 2012 from an academic level I trauma center. Exclusion criteria were known pregnancy or age less than 18 years.

• Intervention 

Three emergency ultrasound fellows performed bedside 4-view basic echocardiographic examinations consisting of subxiphoid, parasternal long, and parasternal short and apical views and made estimates of GCF. The fellows then obtained separate parasternal long-axis views and performed M-mode measurements of the EPSS. Comprehensive TTE was separately performed by cardiac sonographers and LVEF was calculated via the Teichholz method.

• Outcomes  

    • Subjective estimates of GCF categorized as normal systolic function (LVEF > 55%), moderate systolic dysfunction (30% > LVEF > 55%), or severe systolic dysfunction (LVEF < 30%)
    • EPSS measurements
    • Calculated LVEFs also categorized as normal/moderate/severe as above

Results

Calculated LVEF ranged from 13%-86%. EPSS ranged from 0.50-29.70 mm.

Men had higher EPSS scores and higher calculated estimates of LVEF. No other demographic or clinical variables were identified as potential covariates. 

The linear regression model revealed that EPSS is a statistically significant predictor (P < .001) of calculated LVEF.

An EPSS measurement of greater than 7 mm was 100% sensitive and 51.6% specific for severely reduced LVEF. An EPSS measurement of greater than 8 mm was 83.3% sensitive and 50.0% specific for any systolic dysfunction.

Estimated GCF and calculated LVEF were in agreement in 49 (69.0%) of subjects with a weighted Cohen κ of 0.58, with strongest agreement for subjects with severe systolic dysfunction.

epss echo

Strength & Limitations

Strengths:

This study is the first to demonstrate that EPSS can provide a quantitative prediction of LVEF. One strength of this study is the generalizability of the findings given that all indications for TTE were included. Another strength is that the ED ultrasound fellows and cardiac sonographers performed their studies independently, unlike a prior study that utilized the same scans performed by residents to obtain both EPSS and LVEF. 

Limitations:

There were possible misestimations of EPSS in certain pathologic states, such as overestimation of EPSS in mitral stenosis. Additionally, this paper describes the Teichholz method, which is subject to inaccuracies, especially in states of dyskinesis. Of note, the Teichholz method has since been supplanted by the modified Simpson’s rule and is no longer used clinically. On average, time from EPSS measurement to comprehensive echocardiogram was 6 hours with the possibility that systolic function changed during that window of time. Finally, the study size was fairly small with 71 subjects included in the final analysis.

Authors Conclusion

ED physicians can assess left ventricular systolic function using the EPSS, and EPSS is strongly correlated with calculated LVEF. An EPSS greater than 7 mm may be used to predict patients with severely reduced LVEF. ED physician visual estimation was less effective and less consistent than EPSS measurement for predicting systolic function.

Our Conclusion

We agree that EPSS is a feasible and useful tool for assessing systolic function at the bedside. This study establishes that a 7 mm EPSS cutoff is highly sensitive for detecting severe systolic dysfunction. The clinical utility of an EPSS cutoff of 8 mm for any systolic dysfunction is less clear. Employing EPSS measurement with the 7 mm cutoff in mind, in conjunction with visual estimation by an experienced ED sonographer, is likely to provide a more complete picture of a patient’s systolic function at the bedside prior to obtaining a formal echocardiogram.

The Bottom Line 

EPSS measured on bedside ultrasound the ED is an easily obtainable, quantitative predictor of systolic dysfunction. A cutoff of 7mm is sensitive in identifying systolic dysfunction.

Authors

This post was written by Jennie Xu, MS4 at UCSD School of Medicine, Charles Murchison, MD and Amir Aminlari, MD. 

References

McKaigney CJ, Krantz MJ, La Rocque CL, Hurst ND, Buchanan MS, Kendall JL. E-point septal separation: a bedside tool for emergency physician assessment of left ventricular ejection fraction. The American Journal of Emergency Medicine. 2014 Jun 1;32(6):493-7.

 

    1. Labovitz AJ, Noble VE, Bierig M, Goldstein SA, Jones R, Kort S, Porter TR, Spencer KT, Tayal VS, Wei K. Focused cardiac ultrasound in the emergent setting: a consensus statement of the American Society of Echocardiography and American College of Emergency Physicians. Journal of the American Society of Echocardiography. 2010 Dec 1;23(12):1225-30.
    2.  Massie BM, Schiller NB, Ratshin RA, Parmley WW. Mitral-septal separation: new echocardiographic index of left ventricular function. The American journal of cardiology. 1977 Jun 1;39(7):1008-16.
    3. Lew W, Henning H, Schelbert H, Karliner JS. Assessment of mitral valve E point-septal separation as an index of left ventricular performance in patients with acute and previous myocardial infarction. The American journal of cardiology. 1978 May 1;41(5):836-45.
    4. Massie BM, Schiller NB, Ratshin RA, Parmley WW. Mitral-septal separation: new echocardiographic index of left ventricular function. The American journal of cardiology. 1977 Jun 1;39(7):1008-16.