3D echocardiographic global longitudinal strain can identify patients with mildly-to-moderately reduced ejection fraction at higher cardiovascular risk
Severely reduced left ventricular (LV) ejection fraction (EF) derived from 2D echocardiographic (2DE) images is associated with increased mortality and used to guide therapeutic choices. Global longitudinal strain (GLS) is more sensitive than LVEF to detect abnormal LV function, and accordingly may help identify patients with mildly-to-moderately reduced LVEF who are at a similarly high cardiovascular (CV) risk. We hypothesized that 3D echocardiographic (3DE) measurements of EF and GLS, which are more reliable and reproducible, may have even better predictive value than the 2DE indices, and compared their ability to identify such patients. We retrospectively studied 104 inpatients with 2DE-derived LVEF of 30–50% who underwent transthoracic echocardiography during 2006–2010 period, had good quality images, and were followed-up through 2016. Both 2DE and 3DE images were analyzed to measure LVEF and GLS. Kaplan–Meier survival curves were generated for two subgroups defined by the median of each parameter as the cutoff. Of the 104 patients, 32 died of CV related causes. Cox regression revealed that 3D GLS was the only variable associated with CV mortality. Kaplan–Meier curves showed that 2D LVEF, 2D GLS and 3D EF were unable to differentiate patients at higher CV mortality risk, but 3D GLS was the only parameter to do so. Because 3D GLS is able to identify patients with mildly-to-moderately reduced LVEF who are at higher CV mortality risk, its incorporation into clinical decisions may improve survival of those who would benefit from therapeutic interventions not indicated according to the current guidelines.
KeywordsLeft ventricular function Global longitudinal strain Mild to moderately reduced ejection fraction Outcomes Risk assessment
Body surface area
Global longitudinal strain
Speckle tracking echocardiography
Compliance with ethical standards
Conflict of interest
AN was supported by funding from the NIH T32 Training Grant (#(5T32HL7381). The remaining authors have no relevant financial disclosures or conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
The study was approved by the Institutional Review Board with a waiver of consent.
- 2.Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML, Multicenter Automatic Defibrillator Implantation Trial III (2002) Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346:877–883CrossRefGoogle Scholar
- 4.Solomon SD, Anavekar N, Skali H, McMurray JJ, Swedberg K, Yusuf S, Granger CB, Michelson EL, Wang D, Pocock S, Pfeffer MA, Candesartan in Heart Failure Reduction in Mortality I (2005) Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 112:3738–3744CrossRefGoogle Scholar
- 5.Buxton AE, Lee KL, Hafley GE, Pires LA, Fisher JD, Gold MR, Josephson ME, Lehmann MH, Prystowsky EN, Investigators M (2007) Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study. J Am Coll Cardiol 50:1150–1157CrossRefGoogle Scholar
- 7.Morris DA, Otani K, Bekfani T, Takigiku K, Izumi C, Yuda S, Sakata K, Ohte N, Tanabe K, Friedrich K, Kuhnle Y, Nakatani S, Otsuji Y, Haverkamp W, Boldt LH, Takeuchi M (2014) Multidirectional global left ventricular systolic function in normal subjects and patients with hypertension: multicenter evaluation. J Am Soc Echocardiogr 27:493–500CrossRefGoogle Scholar
- 8.Ali MT, Yucel E, Bouras S, Wang L, Fei HW, Halpern EF, Scherrer-Crosbie M (2016) Myocardial strain is associated with adverse clinical cardiac events in patients treated with anthracyclines. J Am Soc Echocardiogr 29(522–527):e3Google Scholar
- 11.Ersboll M, Valeur N, Mogensen UM, Andersen MJ, Moller JE, Velazquez EJ, Hassager C, Sogaard P, Kober L (2013) Prediction of all-cause mortality and heart failure admissions from global left ventricular longitudinal strain in patients with acute myocardial infarction and preserved left ventricular ejection fraction. J Am Coll Cardiol 61:2365–2373CrossRefGoogle Scholar
- 12.Krishnasamy R, Isbel NM, Hawley CM, Pascoe EM, Burrage M, Leano R, Haluska BA, Marwick TH, Stanton T (2015) Left ventricular global longitudinal strain (GLS) is a superior predictor of all-cause and cardiovascular mortality when compared to ejection fraction in advanced chronic kidney disease. PLoS ONE 10:e0127044CrossRefGoogle Scholar
- 13.Nagata Y, Takeuchi M, Wu VC, Izumo M, Suzuki K, Sato K, Seo Y, Akashi YJ, Aonuma K, Otsuji Y (2015) Prognostic value of LV deformation parameters using 2D and 3D speckle-tracking echocardiography in asymptomatic patients with severe aortic stenosis and preserved LV ejection fraction. JACC Cardiovasc Imaging 8:235–245CrossRefGoogle Scholar
- 15.Biering-Sorensen T, Biering-Sorensen SR, Olsen FJ, Sengelov M, Jorgensen PG, Mogelvang R, Shah AM, Jensen JS (2017) Global longitudinal strain by echocardiography predicts long-term risk of cardiovascular morbidity and mortality in a low-risk general population: the Copenhagen City Heart Study. Circ Cardiovasc Imaging 10:e005521Google Scholar
- 17.Maffessanti F, Nesser HJ, Weinert L, Steringer-Mascherbauer R, Niel J, Gorissen W, Sugeng L, Lang RM, Mor-Avi V (2009) Quantitative evaluation of regional left ventricular function using three-dimensional speckle tracking echocardiography in patients with and without heart disease. Am J Cardiol 104:1755–1762CrossRefGoogle Scholar
- 19.Medvedofsky D, Maffessanti F, Weinert L, Tehrani DM, Narang A, Addetia K, Mediratta A, Besser SA, Maor E, Patel AR, Spencer KT, Mor-Avi V, Lang RM (2017) 2D and 3D echocardiography-derived indices of left ventricular function and shape: relationship with mortality. JACC Cardiovasc Imaging 11:1569–1579CrossRefGoogle Scholar
- 20.Baumgartner H, Hung J, Bermejo J, Chambers JB, Edvardsen T, Goldstein S, Lancellotti P, LeFevre M, Miller F Jr, Otto CM (2017) Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr 30:372–392CrossRefGoogle Scholar
- 21.Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, Weissman NJ (2017) Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 30:303–371CrossRefGoogle Scholar
- 22.Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW, Dan A, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Kautzner J, Klempfner R, Kuniss M, Merkely B, Pfeffer MA, Quesada A, Viskin S, McNitt S, Polonsky B, Ghanem A, Solomon SD, Wilber D, Zareba W, Moss AJ (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370:1694–1701CrossRefGoogle Scholar
- 23.Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W, Investigators M-CT (2009) Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361:1329–1338CrossRefGoogle Scholar
- 24.Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M, Cannom D, Daubert JP, Eldar M, Gold MR, Goldberger JJ, Goldenberg I, Lichstein E, Pitschner H, Rashtian M, Solomon S, Viskin S, Wang P, Moss AJ, Investigators M-C (2011) Effectiveness of cardiac resynchronization therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT). Circulation 123:1061–1072CrossRefGoogle Scholar
- 25.Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, Ruddy K, Lenihan D (2017) Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 35:893–911CrossRefGoogle Scholar
- 26.Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C (2017) 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 136:e137–e161CrossRefGoogle Scholar
- 27.Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128:1810–1852CrossRefGoogle Scholar
- 28.Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) 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 28(1–39):e14Google Scholar
- 29.Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Tracy CM, Epstein AE, Darbar D, DiMarco JP, Dunbar SB, Estes NA 3rd, Ferguson TB Jr, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD, College American, American Heart Association Task Force on Practice G, Heart Rhythm S (2012) ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013(61):e6–e75Google Scholar