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Longitudinal Strain and Strain Rate in Patients With Hemodynamically Significant Ventricular Septal Defects Jamie Penk, Angira Patel, Amy Lay and Catherine Webb World Journal for Pediatric and Congenital Heart Surgery 2014 5: 216 DOI: 10.1177/2150135113512334 The online version of this article can be found at: http://pch.sagepub.com/content/5/2/216

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Original Article

Longitudinal Strain and Strain Rate in Patients With Hemodynamically Significant Ventricular Septal Defects

World Journal for Pediatric and Congenital Heart Surgery 2014, Vol. 5(2) 216-218 ª The Author(s) 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2150135113512334 pch.sagepub.com

Jamie Penk, MD1, Angira Patel, MD2, Amy Lay, MD2, and Catherine Webb, MD3

Abstract Background: Patients with significant overcirculation from large ventricular septal defects (VSDs) may have altered contractility compared to normal patients. Methods: Patients were enrolled prospectively. Patients were excluded if they were acutely ill or over age five. Left ventricular longitudinal strain and strain rate were measured in patients with VSDs referred for surgical correction and control participants with structurally normal hearts. Results: There was no difference in the average longitudinal strain or strain rate of six segments in the left ventricle. The mean for both the groups was 19.9% (P ¼ .95). Strain rate was 1.5 s1 in the patients with a VSD and 1.42 s1 in the control group (P ¼ .30). The left ventricular end diastolic dimension was significantly larger in the group with ventricular defects (z score 1.38 vs 0.37) than the control group (P ¼ .000). Conclusions: The left ventricle end-diastolic dimension in patients with ventricular defects was significantly larger, but there was no difference in longitudinal strain or strain rate. Keywords congenital heart disease, strain, ventricular septal defect, echocardiography Submitted June 28, 2013; Accepted October 17, 2013. Presented as a poster abstract at the 8th International Conference of the Pediatric Cardiac Intensive Care Society, Miami Beach, USA; December 8-11, 2010.

Introduction Patients with pulmonary overcirculation from large ventricular septal defects (VSDs) may have altered contractility compared to structurally normal hearts. Systolic dysfunction in patients with VSD has been demonstrated in one previous study,1 but this has not been found consistently. Alternatively, contractility could actually be increased in some patients to compensate for systemic output lost to overcirculation. If a difference in contractility is present, we hypothesized that it may be detectable by strain and strain rate, both of which are sensitive measures of systolic function.2 Speckle tracking has been used to assess longitudinal strain and strain rate in the left ventricle. A difference in strain could lead to a noninvasive assessment tool to help identify children who are more clinically impacted by their VSD. With further study, this could then be used as an additional data point when considering which children with VSDs should be considered for surgical correction. This would be especially useful when the clinical picture is unclear (eg, a patient with VSD, a chronic disease, and failure to thrive) In this study, we hypothesize that patients with clinically significant VSDs have altered contractility. Speckle tracking

is used to assess strain and strain rate in children referred for surgical closure of their VSD and compared the results to children with structurally normal hearts.

Materials and Methods This prospective, blinded, controlled study was approved by the institutional review board and parental consent was obtained prior to enrollment. All patients were enrolled between June 12, 2008, and April 26, 2010. Children referred for surgical closure of VSDs were enrolled, usually on their preoperative visit. Children in the control group were enrolled when study

1 Pediatric Cardiology, Advocate Heart Institute for Children, Oak Lawn, IL, USA 2 Pediatric Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 3 Pediatric Cardiology, C.S. Mott Children’s Hospital, University of Michigan Medical School, Ann Arbor, MI, USA

Corresponding Author: Jamie Penk, 4440 West 95th Street, Oak Lawn, IL 60453, USA. Email: [email protected]

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physicians were available and screening echocardiograms were being performed. Informed consent was obtained prior to obtaining the echocardiographic images. Basic demographic data were recorded. Medication data were obtained from the medical record. Surgical patients were excluded if there were any other congenital heart defects in addition to a VSD. The control participants were eligible if there were no abnormalities detected on their echocardiograms with the exception of a patent foramen ovale. Patients were considered eligible if they met the above-mentioned criteria, were less than six years old, and were not acutely ill. Images were obtained with an ACUSON Sequoia echocardiographic machine (Mountain View, California). Two beat clips were obtained of the left ventricle from the apical view to ensure consistency and limit beat-to-beat variability. In all cases, frame rate was above 60 Hz. The LVEDD was obtained from the final echocardiographic report or measured from study images using M-mode. z scores were generated using EchoIMS (Merge Healthcare, Chicago, Illinois). Postprocessing was performed using Vector Velocity Imaging (VVI) 1.0 speckle tracking software (ACUSON Sequoia) to measure left ventricular, longitudinal strain and strain rate. Figure 1 shows the visual representation of VVI tracking accuracy and at bottom is an example of longitudinal strain curves for six segments of the left ventricle. Peak strain and strain rate were recorded for six segments and were then averaged. Up to two segments could be excluded if the strain curve and visual appearance of the segment indicated poor tracking. If more than two segments were not tracking well, the patient was excluded. Two physicians performed the analysis and were blinded to the patients’ diagnosis. Intra and interobserver variability was determined using 15 patients. Intraobserver reliability was determined by measurements made by the same physician, four weeks apart. The results were calculated using mean and standard deviation. Sample size calculation was performed to detect a difference of 20% between the two groups with a b of 80% and an a of .05. Based on this calculation, 31 patients were needed in each group. Means, medians, range, and standard deviations were calculated using SPSS 12.0 (Chicago, Illinois). Differences between groups were calculated by unpaired t test for continuous variables and chi-square for categorical variables. P value less than .05 was considered statistically significant.

Results A total of 34 patients referred for surgery and 35 control participants were enrolled. Of those, we were able to obtain accurate measurements on 31 in each group. There were 22 females in the VSD group and 11 in the normal group (P ¼ .02). The median age of the normal group was 13.4 months with a range of 0.7 to 63.1 months. The median age of the VSD group was 4.2 months with a range of 0.7 to 33.5 months.

Figure 1. Demonstration of strain results using Vector Velocity Imaging. The top left corner shows a visual representation of tracking accuracy and strain amplitude. The top right has peak strain values reported. The bottom of the figure is an example of longitudinal strain curves with each line representing a different region of the left ventricle through one cardiac cycle.

In the VSD group, ten patients were taking no medications at the time of enrollment. Eleven patients were taking diuretics only. Nine patients were on digoxin in addition to diuretics. Two of those nine were also on enalapril. One final patient was on a diuretic and captopril. Intraobserver variability for the mean longitudinal strain was 4.4% + 3.6% for observer one and 3.6% + 3.6% for observer two. Interobserver variability was 7.4% + 6.6%. In the control group, the mean longitudinal strain was 19.9% with a standard deviation of 2.8%. The mean longitudinal strain was 19.9% with a standard deviation of 4.5% in the VSD group (P ¼ .95). The mean longitudinal strain rate was 1.42 s1 with a standard deviation of 0.25 in the control group and 1.5 s1 with a standard deviation of 0.33 in the VSD group (P ¼ .30). The LVEDD mean z score was 0.37 with a standard deviation of 1.04 in the normal group and 1.38 in the VSD group with a standard deviation of 1.75 (P ¼ .000).

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World Journal for Pediatric and Congenital Heart Surgery 5(2)

Comment Strain and strain rate have been shown to be sensitive indicators of systolic function.2 Despite that, we did not show a difference in strain and strain rate between patients with symptomatic VSDs and patients with structurally normal hearts. We did find that the patients with VSDs have a larger LVEDD than normal individuals as is expected for the physiology of volume overload. A prior study has suggested systolic dysfunction in patients with VSD.1 This study was different in that patients were studied in the catheterization laboratory at baseline conditions and with phenylephrine infusion. Those with VSD and congestive heart failure were not as able to augment left ventricular pressure with phenylephrine infusion resulting in a lower change in pressure over change in time measurement. This suggested a decreased ability to augment systolic function in patients with VSD. The current study evaluates patients with VSD under baseline conditions to determine whether this systolic dysfunction could be detected using strain and strain rate. Another study using echocardiographic indices to assess contractility found no difference in patients with VSD versus normal children under baseline conditions.3 A third study similarly found no difference in contractility between normal children and those with VSD and congestive heart failure by assessing mean velocity of circumferential shortening.4 The current study supports these prior conclusions using a newer technique, strain and strain rate. Larger LVEDD in children with VSD has been shown previously.5 That study did not compare patients with VSD directly to normal children. The current study finds that patients with VSD requiring surgical closure have a larger LVEDD when directly compared to normal children. The female predominance in the VSD group was unexpected and most likely represents a sampling error given our relatively few patients. This difference is unlikely to affect the data, as no difference in strain or strain rate has been shown between the genders.6 There was also a small age difference between the groups. Peak strain does not change with age so this is unlikely to affect our results.6 A small change in strain rate has been found between infants and normal children one to five years of age. In theory, this would mean our normal group should have had lower strain rates than the younger VSD group. However, most of our patients were on the lower end of the one to five age range so any difference should be small. Finally, ten patients were on digoxin or an afterload reducing agent that could affect contractility. This potential confounder was intentionally left in the study as we aimed for clinically relevant results and thought it unlikely that clinicians would take patients off medications in order to do a strain analysis. Our numbers are too small to make a reasonable subanalysis, but these medications could have affected our results.

Further limitations of this study include lack of hemodynamic data on Qp: Qs or historical data to assess degree of congestive heart failure. The decision to refer to surgery was based on the opinion of the treating cardiologist and the agreement of our cardiology group and surgeon. The large difference in LVEDD does suggest that the group referred for surgery had significant overcirculation. In addition, other assessments of strain including radial or circumferential strain were not assessed due to limitations in the software available. Contractility as measured by left ventricular longitudinal strain and strain rate was not different between patients with VSD referred for surgery and normal children under baseline conditions. This suggests that contractility as measured by a sensitive echocardiographic measure is not affected by a clinically significant VSD. The LVEDD of patients referred for surgical closure of their VSD are dilated compared to normal patients. Further studies using radial and circumferential strain are warranted to evaluate global contractility. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References 1. Stewart JM, Hintze TH, Woolf PK, Snyder MS, Seligman KP, Gewitz MH. Nature of heart failure in patients with ventricular septal defect. Am J Physiol. 1995;269(4 pt 2): H1473-H1480. 2. Geyer H, Caracciolo G, Abe H, et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23(4): 351-369. 3. Kimball TR, Daniels SR, Meyer RA, Hannon DW, Khoury P, Schwartz DC. Relation of symptoms to contractility and defect size in infants with ventricular septal defect. Am J Cardiol. 1991; 67(13): 1097-1102. 4. Corin WJ, Swindle MM, Spann JF, et al. Mechanism of decreased forward stroke volume in children and swine with ventricular septal defect and failure to thrive. J Clin Invest. 1988:82(2): 544-551. 5. Kleinman C, Tabibian M, Starc T, Hsu D, Gersony W. Spontaneous regression of left ventricular dilation in children with restrictive ventricular septal defects. J Pediatr. 2007;150(6): 583-586. 6. Lorch S, Ludomirsky A, Singh G. 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(11): 1207-1215.

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Longitudinal strain and strain rate in patients with hemodynamically significant ventricular septal defects.

Patients with significant overcirculation from large ventricular septal defects (VSDs) may have altered contractility compared to normal patients...
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