Ref 1. Ref 2. Ref 3. Ref 4. See graph

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1 Ref 1 Ref 2 Ref 3 1. Ages 6-23 y/o 2. Significant LVM differences by gender 3. For males 95 th percentiles: a. LVM/BSA = 103 b. LVM/height = For females 95 th percentiles: a. LVM/BSA = 84 b. LVM/height = Ages 6-17 y/o 2. Significant LVM differences by gender males avg 99 g, females avg 80 g 3. Across races and genders - Indexing by LV mass /height **3 provided the best correlation with LV mass/lean body mass compared to indexing with a. BSA b. Height c. Height **2 d. Height ** For entire group (all races and genders) 95 th percentiles: a. LVM/BSA = 89 b. LVM/height = 85 c. LVM/height **2 = 52 d. LVM/height **2.7 =39 e. LVM/height**3 = The method of correcting LVM for body size and the criteria used to define LVH have varied between studies 2. Because of the rise in the prevalence of obesity, indexing of LVM to weight or body surface area may allow an increased LVM to be interpreted erroneously as normal. Height2.7 (in meters) has been validated as an indicator of lean body mass and has been recommended for indexing LVM. Use of height2.7 to index LVM also minimizes the effect of age, gender, and race.10,11 3. LVH by adult criteria was defined as LVMI > 51 g/m2.7 and by pediatric criteria as LVMI > 38.6 g/m2.7. Ref 4 See graph

2 Ref 5 Adult values See Table 1. Women LVM/BSA < Men LVM/BSA < 115 Ref 6 ASE Peds Quantification paper Not much help. Ref 7 (agrees with Ref 3) adults and 444 infants to young adults 2. Normalizations of left ventricular mass for height or body surface area introduce artifactual relations of indexed ventricular mass to body size and errors in estimating the impact of overweight. These problems are avoided and variability among normal subjects is reduced by using left ventricular mass/height**2.7 Ref 8 Ref 9 1. Scaling LV mass to BSA in children results in less misclassification with respect to LVH than does scaling to height. 2. Ours is not the first study to conclude that height based LV mass normalization results in overestimation of the prevalence of LVH among the obese. A number of controversies surround the measurement of LV mass. There are significant problems in standardizing echocardiographic measurement of LV mass across echocardiography laboratories. Historically, one method for overcoming this variability in adults is to index the LV mass to body size, most commonly BSA, height in meters squared, or to the 2.7th power [10]. Dividing LV mass by height to the power of 2.7 accounts for LV mass and scaling myocardial mass to body size. This useful application has been adapted in children to compensate for normal growth [11]. However, this indexing method is also limited in the pediatric population because LVMI2.7 increases with decreasing height [7]. Numerous studies have shown that LVMI2.7 overestimates LV mass in adults [5]. Foster et al. [9] showed that expressing LV mass relative to BSA or height has limitations in the pediatric population because LV mass

3 varies in proportion to lean body mass; however scaling LV mass to BSA in children appears to be better than scaling to height. Ref 10 The children and adolescents who have elevated BMI (overweight and obese) with NWC (normal waist circumference) had LVM and LBM similar to normal controls with NWC despite having an elevated BMI and elevated non-lbmi (as an estimation of adipose tissue). Additionally, similar to normal controls, those subjects with elevated BMI and NWC had a stronger correlation between LVM and LBM than subjects with elevated BMI with IWC (increased waist circumference). Ref 11 LVM scaled by height **2.7 > 9 y/o > 40 in girls and > 45 in boys is abnormal Under 9 y/o must use curves

4 References 1. S. Daniels, et al. Echocardiographically Determined Left Ventricular Mass Index in Normal Children, Adolescents, and Young Adults J Am Coll Cardiol 1988;12: S. Daniels, et al. Indexing Left Ventricular Mass to Account for Differences in Body size Am J Cardiol 1995;76: Hanevold C, The Effects of Obesity, Gender, and Ethnic Group on Left Ventricular Hypertrophy and Geometry in Hypertensive Children: A Collaborative Study of the International Pediatric Hypertension Association. Pediatrics 2004;113: Cain PA. et al. Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study. BMC Medical Imaging ASE Recommendations for Chamber Quantification: A Report from the American Society of Echocardiography s Guidelines and Standards Committee and the Chamber Quantification Writing Group, Developed in Conjunction with the European Association of Echocardiography, a Branch of the European Society of Cardiology. JASE 2005 Vol 14;12: ASE Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram: A Report From the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. JASE 2010;23: De Simone G, et al. Left Ventricular Mass and Body Size in Normotensive Children and Adults: Assessment of Allometric Relations and Impact of Overweight. J Am Coli CardioI1992;20: Foster et, al Limitations of expressing LV mass relative to height and to BSA in children. JASE 2013;26: Mirchandani D, et al. Concordance of measures of left-ventricular hypertrophy in pediatric hypertension Pediatric Cardiology, Pediatr Cardiol Apr;35(4): doi: /s Epub 2013 Nov Am J Cardiol Mar 15;113(6): doi: /j.amjcard Epub 2013 Dec 25. Left ventricular mass in children and adolescents with elevated body mass index and normal waist circumference. Mehta SK. 11. Khoury et al JASE 2009;22: Age specific reference intervals for indexed left ventricular mass in children

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8 Colan, et al. JACC 1984;4:715-24

9 (J Am Soc Echocardiogr 2007;20:

10 Figure 7. Centile chart of the quotient of early to atrial filling phase peak flow velocity (E/A Vmax). Numerical values are displayed in the table. The asterisk in the table labels median, P5 and P95 of infants aged 2 to 5 months (n = 42). The dashed line represents P90 in the subpopulation with high heart rates and signal superimposition (EA). Decreasing heart rate (HR ) influences parameter expression in age groups 2 through 5. P = percentile. JACC Volume 32, Issue 5, 1 November 1998, Pages Ggg

11 Journal of the American College of Cardiology Volume 32, Issue 5, November 1998

12 Journal of the American Society of Echocardiography , DO

13 1. Report Left Atrial Filling Pressures Depressed EF Intact EF J Am Soc Echocardiogr 2009;22: J Am Soc Echocardiogr 2007;20: JACC 1998;32: Grade Diastolic (Dx) Function (Fx) E/A below normal (adult < 1) normal LAP E/e 8 normal LAP E/A normal but suspect pseudo normal E/e 9-14 Indeterminate E/A above normal (adult > 2) LAP E/e 15 LAP E/e 8 normal LAP LA vol < 34 ml/m2 Normal LAP E/e 9-14 E/e 15 LA vol 34 ml/m2 LAP LAP e normal (adult Sept e 8 Lat e 10) LA vol < 34 ml/m2 Normal DxFx LA vol 34 ml/m2 Normal DxFx or Athlete or Constriction E/e 8 Grade 1 e abnorml (adult Sept e < 8 Lat e < 10) E/e 9-14 Grade 2 E/e 15 Grade 3

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15 Journal Copyright Journal of of the the American 2009 American American Society Society of Society Echocardiography of Echocardiography of , DOI: Terms 22, DOI: and ( /j.echo ggggggg Conditions ( /j.echo )

16 Echocardiographic Parameter Severity Guidelines* Valve Stenosis Normal Mild Severe Aortic Stenosis - Mean Gradient < 25 mm Hg > 50 mm Hg - Peak Gradient < 30 mm Hg > 70 mm Hg - Peak velocity < 1.8 m/sec VTI Ratio (VTI-LVOT/VTI-AoV) > < 0.25 =CSA-LVOT/CSA-AoV ( Pulmonary Stenosis - Mean Gradient < 20 mm Hg > 40 mm Hg - Peak Gradient < 30 mm Hg > 60 mm Hg - velocity < 1.5 m/sec Peripheral Pulmonary stenosis <1.5 m/sec >= 2 m/sec, <? > 60 mm Hg? Mitral Stenosis - Mean Gradient < 6 mm Hg > 12 mm Hg - Peak velocity < 1.3 m/sec Tricuspid Stenosis - Mean Gradient < 5 mm Hg > 10 mm Hg - Peak velocity < 1.0 m/sec Valve Regurgitation Mild Severe Aortic regurgitation - decay slope < 2 m/sec-sec > 3 m/sec-sec - pressure half time < ms Systolic Function Hyperdynamic Mildly Decreased Severely Decreased LV Fractional Shortening > 45% 20%-25% < 15% LV Ejection Fraction > 75% 45%-54% < 30% RV Ejection Fraction? 35%-45%?? Systolic and Diastolic Function Normal Indeterminate Abnormal Mitral Valve E/Ea < > 15 RV dp/dt??? LV dp/dt > 1200 Hg/s Hg/s < 1000 Hg/s Systolic and Diastolic Function Normal Range Alternative - Abnormal IVRT_corrected 63 +/- 7 msec MPI (Tei Index) LV?0.35 +/- 0.05? < 0.40 MPI (Tei index) RV?0.32 +/- 0.05? Color M Mode Prop Vel Slope > 50 > 45 PHTN Mild PHTN Severe PHTN Alternative TR Gradient mm Hg >65 mm Hg report % of systemic Z Scores Mildly Abnormal Moderately Abn Severely Abnormal Z Scores (negative) -3.0 < z < < z < -3.0 z < -5.0 Z scores (positive) 2.0 < z < < z < 5.0 z > 5.0 Assessment of Tamponade Physiology, Respiratory Variability Normal Other MV inflow (peak or VTI) < 25 % any degree of RV diastolic collapse TV inflow (peak or VTI) < 40% prolonged (>1/3 card cycle) RA collapse * these are simply guidelines. Of course one has to take into account co-existing conditions such as cardiac function, valve regurgitation, heart rate, age, etc. when making such determination of severity

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