philip Levy, Washing University School of Medicine
16 September 2015
I read with great interest the study by Jashari et al. (Cardiovascular Ultrasound (2015) 13:37) on Normal ranges of left ventricular strain in children: a meta-analysis. [1] Clinical application of cardiac strain by two dimensional speckle tracking echocardiography to measure LV function in children requires knowledge of the range of normal values. [2-6] These reference values and associated variations of these strain values need to be “firmly established before routine clinical adoption” of LV strain measurements can be implemented in children. [2-6] The authors modeled their meta-analysis after the manuscript by Levy et al. on Normal Ranges of Right Ventricular Systolic and Diastolic Strain Measures in Children: A Systematic Review and Meta-Analysis.[3] Similar to Yingchoncharoen et al’s. and Marwick et al’s.[2] 2012 meta- analysis of the normal ranges of left ventricular strain in adults, Levy et al. sought to define a range of normal RV strain measures using a compilation of all studies that reported values for cohorts of normal or control children. [3] Levy et al. intended that their manuscript on normal values of RV strain in children would serve as a reference for other authors wishing to replicate, update, and define reference ranges on the basis on a systemic review and meta-analysis with other novel cardiac measures in children and neonates.[3] Jashari et al. has properly referenced the work by Levy et al. and Yingchoncharoen and Marwick et al.
Recent recommendations from the European Association of Cardiovascular Imaging (EACVI) and the American Society Echocardiography (ASE) Industry Task Force to standardize strain imaging and reduce inter-vendor differences and ambiguities in the strain algorithms emphasize that the proper utilization of the strain imaging protocols and reference values will provide a valid basis that allows comparison between studies and “more meaningful clinical applications.” [5,6] Reference ranges and the causes of the reported variation of LV global longitudinal, circumferential, and radial strain established by this meta-analysis coupled the work from the EACVI/ASE Industry Task Force will allow deformation imaging to be used more routinely to assess clinical changes in cardiac function “across a broad range of physiologic and pathologic conditions in children.”[2-6] Reference values using speckle-tracking echocardiography in children would inform both the clinical decision-making and investigation of pathogenesis of certain cardiopulmonary pathologies in this cohort.[2-6] This is a straightforward topic with clinical implications and Jashari et al. provide the framework for a meta-analysis. However, there are a few major key components missing from the search methods, selection criteria, and linked conclusions that should be made clear for the interpretation of the results of this manuscript.
In planning the search process, the Cochrane Handbook for systematic reviews of interventions by Higgins and Green state that utilizing and documenting the guidance of a local healthcare librarian or information specialist with experience of conducting searches for systematic reviews is a necessity in performing and validating meta-analysis research.[7] The authors used five search engines and identified 282 potential articles. In designing the search strategy, the authors applied “key terms” in the search process as opposed to “search hedges.” The use of search hedges that cover concepts using terms harvested from standard term indices and on-topic articles have been shown to identify more potential relevant articles than “key terms”, and in some cases doubles the amount of articles.[3,7]. Failing to use search hedges has led the Jashari et al. to miss several potential manuscripts and datasets [8-20] that would have increased the number of potential articles and potentially alter their conclusions with respects to identifying confounders that may contribute to differences in reported measures. Furthermore, the authors may have been able to perform a meta-analysis with global circumferential and radial strain with increased number of datasets.
The authors elected not to incorporate studies with missing data raising the possibility that the observed effect estimate is biased.[7] Incomplete data sets do exist, but all authors of potential relevant eligible studies should be contacted by e-mail to a) notify them of the meta-analysis and b) to obtain any missing information not reported in their individual studies. [3] If authors do not respond, then it is up to the authors of the manuscript to either include or exclude, but proper protocol must be clearly documented enough to ensure reproducibility of the meta-analysis.[3,7] The authors appropriately remark how duplicates or triplicates form the search analysis was handled, but they still included manuscripts that had overlapping dataset and skewing the statistical analysis.[21,22]
LV global longitudinal strain and strain rate calculated from segmental averaging of the three apical views, apical 4-, 3-, and 2- chambers and artciles that reported Global strain were included in this meta-analysis. Clinically, longitudinal strain is still reported from the weighted average of the six segments from the apical four-chamber view and circumferential and radial strain is reported from weighted average of the six segments from the mid-ventricular level at the papillary muscle. [5,6] The authors correctly stratified their meta-analysis by these different approaches. However, the work by Lorch et al. on maturational and Growth-Related changes in left ventricular longitudinal strain in children was not included because the study “did not measure longitudinal strain of the whole LV”. [23] In fact, Lorch et al. used the 4-chamber view to measure longitudinal strain from the whole LV.
The authors conclude that the “vendor” significantly determined the variations in radial strain values. This may be so based on the data sets included in this meta-analysis, however the methodology to identify data sets in this analysis missed data-sets [8-20] that may be have altered this conclusion. On the other hand, the recent EACVI/ASE Industry Task Force has only published results that compared longitudinal strain imaging from seven different ultrasound vendors and platforms.[6] LV global longitudinal strain was chosen by the task force as its first target strain measure because it appeared the easiest to define, the most robust, and therefore the closest to routine clinical use.[6] The initial conclusions from this meta-analysis appear to support this claim.
The above technical points do not limit the documented reference ranges of longitudinal, circumferential, or radial strain in children in the meta-analysis by Jashari et al., but may alter some of the linked conclusions with respects to identifying the confounders (i.e age and vendor) that contribute to differences in reported measures. Some of the pitfalls experienced with this meta-analysis are unavoidable, but they highlight the importance of including a trained librarian in the planning, searching, and execution of systematic reviews and meta-analysis that will remove much of the bias and enhance and validate the linked conclusions.
References
1. Jashari H, Rydberg A, Ibrahimi P, Bajraktari G, Kryeziu L, Jashari F, et al. Normal ranges of left ventricular strain in children: a meta-analysisCardiovascular Ultrasound (2015) 13:37)
2. Yingchoncharoen T, Agarwal S, Popovic ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr 2013;26: 185-91.
3. Levy PT, Sanchez A, Machefsky A, Fowler S, Holland MR, Singh GK. Normal ranges of right ventricular systolic and diastolic strain measures in children: a systematic review and meta-analysis. J Am Soc Echocardiogr 2014;27:549–60.
4. Kaul S, Miller JG, Grayburn PA, Hashimoto S, Hibberd M, Holland MR, et al. A suggested roadmap for cardiovascular ultrasound research for the future. J Am Soc Echocardiogr 2011;24:455-64. nalysis. J Am Soc Echocardiogr 2014;27:549–60.
5. Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, et al. Definitions for a Common Standard for 2D Speckle Tracking Echocardiography: Consensus Document of the EACVI/ASE/Industry Task Force to Standardize Deformation Imaging. J Am Soc Echocardiogr 2015;28:183–93.
6. Farsalinos KE, Daraban AM, Ünlü S, Thomas JD, Badano LP, Voigt JU. Head-to-Head Comparison of Global Longitudinal Strain Measurements among Nine Different Vendors. J Am Soc Echocardiogr 2015;1–13 (Ahead of Print).
7. Higgins JPT, Green S. Cochrane handbook for systematic reviews of inter- ventions: Cochrane book series. Copenhagen, Denmark: Cochrane Collaboration; 2008.
8. Moiduddin N, Texter KM, Zaidi AN, Herskenson JA, Stefaniak CA, Hayes J, et al. Two-dimensional speckle strain and dyssynchrony in single right ventricles versus normal right ventricles. J Am Soc Echocardiogr 2010;23:673-97.
9. Blanc J, Stos B, de Montalembert M, Bonnet D, Boudjemline Y. Right ventricular systolic strain is altered in children with sickle cell disease. J Am Soc Echocardiogr 2012;25:511-7.
10 .Sato Y, Maruyama A, Ichihashi K.. Myocardial strain of the left ventricle in normal children. Journal of Cardiology. J Cardiol 2012;60:145-9
11. Malev E, Zemtsovsky E, Pshepiy A, Timofeev E, Reeva S, Prokudina M. Evaluation of left ventricular systolic function in young adults with mitral valve prolapse. Exp Clin Cardiol 2012;17:165–8.
12. Hauser M, Kuehn A, Petzuch C, Schoen P, Elmenhorst J, Schoenfelder M, et al. The Munich Triathlon Heart Study: ventricular function, myocardial velocities and 2-D strain in healthy children before and after endurance stress. Pediatr Cardiol 2013;34:576-82.
13. Black D, Bryant J, Peebles C, Davies L, Inskip H, Godfrey K, et al. Increased regional deformation of the left ventricle in normal children with increased body mass index: Implications for future cardiovascular health. Pediatric cardiol 2014;35:315–22.
14. Roberson DA, Cui W. Tissue Doppler Imaging Measurement of Left Ventricular Systolic Function in Children: Mitral Annular Displacement Index Is Superior to Peak Velocity. J Am Soc Echocardiogr 2009;22:376-82.
15. Laser KT, Haas NA, Fischer M, Habash S, Degener F, Prinz C, et al. Left ventricular rotation and right–left ventricular interaction in congenital heart disease: the acute effects of interventional closure of patent arterial ducts and atrial septal defects. Cardiol Young 2013;24:661–74.
16. Mangner N, Scheuermann K, Winzer E, Wagner I, Hoellriegel R, Sandri M, et al. Childhood Obesity Impact on Cardiac Geometry and Function. JACC Cardiovasc Imaging. 2014;7:1198-1205.
17. Koenigstein K, Raedle-Hurst T, Hosse M, Hauser M, Abdul-Khaliq H.. Altered Diastolic Left Atrial and Ventricular Performance in Asymptomatic Patients After Repair of Tetralogy of Fallot. Pediatric cardiology. 2012:1–6.
18. Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N, et al. Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle (JUSTICE) study. Circ J 2012;76:2623–32.
19. Li Y, Xie M, Wang X, Lü Q, Zhang L, Ren P. Impaired right and left ventricular function in asymptomatic children with repaired tetralogy of fallot by two-dimensional speckle tracking echocardiography study. Echocardiography 2015;32:135-43.
20. Al-Biltagi M, Rab OA, Tolba E, Rowisha MA, El-Sayed Mahfouz A, Elewa MA.. Speckle Tracking and Myocardial Tissue Imaging in Infant of Diabetic Mother with Gestational and Pregestational Diabetes. Pediatric cardiol 2014;36:445–53.
21. Forsey J, Benson L, Rozenblyum E, Friedberg MK, Mertens L. Early changes in apical rotation in genotype positive children with hypertrophic cardiomyopathy mutations without hypertrophic changes on 2D imaging. J Am Soc Echocardiogr. 2014;27:215-21.
22. Fernandes FP, Manlhiot C, Roche SL, Grosse-Wortmann L, Slorach C, McCrindle BW, et al. Impaired left ventricular myocardial mechanics and their relation to pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot. J Am Soc Echocardiogr 2012;25:494–503.
23. Lorch SM, Ludomirsky A, Singh GK. Maturational and growth-related changes in left ventricular longitudinal strain and strain rate measured by two-dimensional speckle tracking echocardiography in healthy pediatric population. J Am Soc Echocardiogr 2008;21:1207-15
Competing interests
Our group has previously published a detailed meta-analysis on normal values RV Strain in Children. (J Am Soc Echocardiogr 2014;27:549-60). We modeled it after the landmark work by Yingchoncharoen and Marwick et al and properly credited them with introducing meta-analysis research to the field of strain imaging. Our own group has been working since 2013 on a similar meta-analysis of reference values of LV strain in children that was submitted for recently review. The meta-analysis by Jashari et al. is extremely well done and is similar to my group’s results (in regards to the reference values). We are extremely pleased to see that it was published, as these types of studies can only enhance the growing field of strain imaging in children. However, as I outlined in a letter above, the work by Jashari et al. has some limitations that may alter the linked conclusions that your readership should understand as they interpret the associated confounders that may affect reported normal values of LV strain in children.
Letter to the Editor
16 September 2015
I read with great interest the study by Jashari et al. (Cardiovascular Ultrasound (2015) 13:37) on Normal ranges of left ventricular strain in children: a meta-analysis. [1] Clinical application of cardiac strain by two dimensional speckle tracking echocardiography to measure LV function in children requires knowledge of the range of normal values. [2-6] These reference values and associated variations of these strain values need to be “firmly established before routine clinical adoption” of LV strain measurements can be implemented in children. [2-6] The authors modeled their meta-analysis after the manuscript by Levy et al. on Normal Ranges of Right Ventricular Systolic and Diastolic Strain Measures in Children: A Systematic Review and Meta-Analysis.[3] Similar to Yingchoncharoen et al’s. and Marwick et al’s.[2] 2012 meta- analysis of the normal ranges of left ventricular strain in adults, Levy et al. sought to define a range of normal RV strain measures using a compilation of all studies that reported values for cohorts of normal or control children. [3] Levy et al. intended that their manuscript on normal values of RV strain in children would serve as a reference for other authors wishing to replicate, update, and define reference ranges on the basis on a systemic review and meta-analysis with other novel cardiac measures in children and neonates.[3] Jashari et al. has properly referenced the work by Levy et al. and Yingchoncharoen and Marwick et al.
Recent recommendations from the European Association of Cardiovascular Imaging (EACVI) and the American Society Echocardiography (ASE) Industry Task Force to standardize strain imaging and reduce inter-vendor differences and ambiguities in the strain algorithms emphasize that the proper utilization of the strain imaging protocols and reference values will provide a valid basis that allows comparison between studies and “more meaningful clinical applications.” [5,6] Reference ranges and the causes of the reported variation of LV global longitudinal, circumferential, and radial strain established by this meta-analysis coupled the work from the EACVI/ASE Industry Task Force will allow deformation imaging to be used more routinely to assess clinical changes in cardiac function “across a broad range of physiologic and pathologic conditions in children.”[2-6] Reference values using speckle-tracking echocardiography in children would inform both the clinical decision-making and investigation of pathogenesis of certain cardiopulmonary pathologies in this cohort.[2-6] This is a straightforward topic with clinical implications and Jashari et al. provide the framework for a meta-analysis. However, there are a few major key components missing from the search methods, selection criteria, and linked conclusions that should be made clear for the interpretation of the results of this manuscript.
In planning the search process, the Cochrane Handbook for systematic reviews of interventions by Higgins and Green state that utilizing and documenting the guidance of a local healthcare librarian or information specialist with experience of conducting searches for systematic reviews is a necessity in performing and validating meta-analysis research.[7] The authors used five search engines and identified 282 potential articles. In designing the search strategy, the authors applied “key terms” in the search process as opposed to “search hedges.” The use of search hedges that cover concepts using terms harvested from standard term indices and on-topic articles have been shown to identify more potential relevant articles than “key terms”, and in some cases doubles the amount of articles.[3,7]. Failing to use search hedges has led the Jashari et al. to miss several potential manuscripts and datasets [8-20] that would have increased the number of potential articles and potentially alter their conclusions with respects to identifying confounders that may contribute to differences in reported measures. Furthermore, the authors may have been able to perform a meta-analysis with global circumferential and radial strain with increased number of datasets.
The authors elected not to incorporate studies with missing data raising the possibility that the observed effect estimate is biased.[7] Incomplete data sets do exist, but all authors of potential relevant eligible studies should be contacted by e-mail to a) notify them of the meta-analysis and b) to obtain any missing information not reported in their individual studies. [3] If authors do not respond, then it is up to the authors of the manuscript to either include or exclude, but proper protocol must be clearly documented enough to ensure reproducibility of the meta-analysis.[3,7] The authors appropriately remark how duplicates or triplicates form the search analysis was handled, but they still included manuscripts that had overlapping dataset and skewing the statistical analysis.[21,22]
LV global longitudinal strain and strain rate calculated from segmental averaging of the three apical views, apical 4-, 3-, and 2- chambers and artciles that reported Global strain were included in this meta-analysis. Clinically, longitudinal strain is still reported from the weighted average of the six segments from the apical four-chamber view and circumferential and radial strain is reported from weighted average of the six segments from the mid-ventricular level at the papillary muscle. [5,6] The authors correctly stratified their meta-analysis by these different approaches. However, the work by Lorch et al. on maturational and Growth-Related changes in left ventricular longitudinal strain in children was not included because the study “did not measure longitudinal strain of the whole LV”. [23] In fact, Lorch et al. used the 4-chamber view to measure longitudinal strain from the whole LV.
The authors conclude that the “vendor” significantly determined the variations in radial strain values. This may be so based on the data sets included in this meta-analysis, however the methodology to identify data sets in this analysis missed data-sets [8-20] that may be have altered this conclusion. On the other hand, the recent EACVI/ASE Industry Task Force has only published results that compared longitudinal strain imaging from seven different ultrasound vendors and platforms.[6] LV global longitudinal strain was chosen by the task force as its first target strain measure because it appeared the easiest to define, the most robust, and therefore the closest to routine clinical use.[6] The initial conclusions from this meta-analysis appear to support this claim.
The above technical points do not limit the documented reference ranges of longitudinal, circumferential, or radial strain in children in the meta-analysis by Jashari et al., but may alter some of the linked conclusions with respects to identifying the confounders (i.e age and vendor) that contribute to differences in reported measures. Some of the pitfalls experienced with this meta-analysis are unavoidable, but they highlight the importance of including a trained librarian in the planning, searching, and execution of systematic reviews and meta-analysis that will remove much of the bias and enhance and validate the linked conclusions.
References
1. Jashari H, Rydberg A, Ibrahimi P, Bajraktari G, Kryeziu L, Jashari F, et al. Normal ranges of left ventricular strain in children: a meta-analysisCardiovascular Ultrasound (2015) 13:37)
2. Yingchoncharoen T, Agarwal S, Popovic ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr 2013;26: 185-91.
3. Levy PT, Sanchez A, Machefsky A, Fowler S, Holland MR, Singh GK. Normal ranges of right ventricular systolic and diastolic strain measures in children: a systematic review and meta-analysis. J Am Soc Echocardiogr 2014;27:549–60.
4. Kaul S, Miller JG, Grayburn PA, Hashimoto S, Hibberd M, Holland MR, et al. A suggested roadmap for cardiovascular ultrasound research for the future. J Am Soc Echocardiogr 2011;24:455-64. nalysis. J Am Soc Echocardiogr 2014;27:549–60.
5. Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, et al. Definitions for a Common Standard for 2D Speckle Tracking Echocardiography: Consensus Document of the EACVI/ASE/Industry Task Force to Standardize Deformation Imaging. J Am Soc Echocardiogr 2015;28:183–93.
6. Farsalinos KE, Daraban AM, Ünlü S, Thomas JD, Badano LP, Voigt JU. Head-to-Head Comparison of Global Longitudinal Strain Measurements among Nine Different Vendors. J Am Soc Echocardiogr 2015;1–13 (Ahead of Print).
7. Higgins JPT, Green S. Cochrane handbook for systematic reviews of inter- ventions: Cochrane book series. Copenhagen, Denmark: Cochrane Collaboration; 2008.
8. Moiduddin N, Texter KM, Zaidi AN, Herskenson JA, Stefaniak CA, Hayes J, et al. Two-dimensional speckle strain and dyssynchrony in single right ventricles versus normal right ventricles. J Am Soc Echocardiogr 2010;23:673-97.
9. Blanc J, Stos B, de Montalembert M, Bonnet D, Boudjemline Y. Right ventricular systolic strain is altered in children with sickle cell disease. J Am Soc Echocardiogr 2012;25:511-7.
10 .Sato Y, Maruyama A, Ichihashi K.. Myocardial strain of the left ventricle in normal children. Journal of Cardiology. J Cardiol 2012;60:145-9
11. Malev E, Zemtsovsky E, Pshepiy A, Timofeev E, Reeva S, Prokudina M. Evaluation of left ventricular systolic function in young adults with mitral valve prolapse. Exp Clin Cardiol 2012;17:165–8.
12. Hauser M, Kuehn A, Petzuch C, Schoen P, Elmenhorst J, Schoenfelder M, et al. The Munich Triathlon Heart Study: ventricular function, myocardial velocities and 2-D strain in healthy children before and after endurance stress. Pediatr Cardiol 2013;34:576-82.
13. Black D, Bryant J, Peebles C, Davies L, Inskip H, Godfrey K, et al. Increased regional deformation of the left ventricle in normal children with increased body mass index: Implications for future cardiovascular health. Pediatric cardiol 2014;35:315–22.
14. Roberson DA, Cui W. Tissue Doppler Imaging Measurement of Left Ventricular Systolic Function in Children: Mitral Annular Displacement Index Is Superior to Peak Velocity. J Am Soc Echocardiogr 2009;22:376-82.
15. Laser KT, Haas NA, Fischer M, Habash S, Degener F, Prinz C, et al. Left ventricular rotation and right–left ventricular interaction in congenital heart disease: the acute effects of interventional closure of patent arterial ducts and atrial septal defects. Cardiol Young 2013;24:661–74.
16. Mangner N, Scheuermann K, Winzer E, Wagner I, Hoellriegel R, Sandri M, et al. Childhood Obesity Impact on Cardiac Geometry and Function. JACC Cardiovasc Imaging. 2014;7:1198-1205.
17. Koenigstein K, Raedle-Hurst T, Hosse M, Hauser M, Abdul-Khaliq H.. Altered Diastolic Left Atrial and Ventricular Performance in Asymptomatic Patients After Repair of Tetralogy of Fallot. Pediatric cardiology. 2012:1–6.
18. Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N, et al. Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle (JUSTICE) study. Circ J 2012;76:2623–32.
19. Li Y, Xie M, Wang X, Lü Q, Zhang L, Ren P. Impaired right and left ventricular function in asymptomatic children with repaired tetralogy of fallot by two-dimensional speckle tracking echocardiography study. Echocardiography 2015;32:135-43.
20. Al-Biltagi M, Rab OA, Tolba E, Rowisha MA, El-Sayed Mahfouz A, Elewa MA.. Speckle Tracking and Myocardial Tissue Imaging in Infant of Diabetic Mother with Gestational and Pregestational Diabetes. Pediatric cardiol 2014;36:445–53.
21. Forsey J, Benson L, Rozenblyum E, Friedberg MK, Mertens L. Early changes in apical rotation in genotype positive children with hypertrophic cardiomyopathy mutations without hypertrophic changes on 2D imaging. J Am Soc Echocardiogr. 2014;27:215-21.
22. Fernandes FP, Manlhiot C, Roche SL, Grosse-Wortmann L, Slorach C, McCrindle BW, et al. Impaired left ventricular myocardial mechanics and their relation to pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot. J Am Soc Echocardiogr 2012;25:494–503.
23. Lorch SM, Ludomirsky A, Singh GK. Maturational and growth-related changes in left ventricular longitudinal strain and strain rate measured by two-dimensional speckle tracking echocardiography in healthy pediatric population. J Am Soc Echocardiogr 2008;21:1207-15
Competing interests
Our group has previously published a detailed meta-analysis on normal values RV Strain in Children. (J Am Soc Echocardiogr 2014;27:549-60). We modeled it after the landmark work by Yingchoncharoen and Marwick et al and properly credited them with introducing meta-analysis research to the field of strain imaging. Our own group has been working since 2013 on a similar meta-analysis of reference values of LV strain in children that was submitted for recently review. The meta-analysis by Jashari et al. is extremely well done and is similar to my group’s results (in regards to the reference values). We are extremely pleased to see that it was published, as these types of studies can only enhance the growing field of strain imaging in children. However, as I outlined in a letter above, the work by Jashari et al. has some limitations that may alter the linked conclusions that your readership should understand as they interpret the associated confounders that may affect reported normal values of LV strain in children.