Left Ventricular Volumes, Mass and Function Normalized to the Body Surface Area, Age and Gender From CMR in a Large Cohort of Well-Treated Thalassemia Major Patients without Myocardial Iron Overload
Authors: Meloni Antonella , Aquaro Giovanni , Festa Pierluigi , Gagliardotto Francesco , Zuccarelli Angelo , Gerardi Calogera , Santodirocco Michele , Romeo Maria Antonietta , Gamberini Maria Rita , Smacchia Maria Paola , Palazzi Giovanni , Chiodi Elisabetta , De Franceschi Lucia , Positano Vincenzo , Lombardi Massimo , Pepe Alessia 
Published: October 2019

Abstract
Abstract 1090
Introduction. Cardiovascular Magnetic Resonance (CMR) allows an accurate and reproducible quantification of left ventricular (LV) parameters. In Thalassemia major (TM) patients different “normal” LV values have been reported due to chronic anemia and eventually pre-existing iron burdens. Moreover, in this population it is unknown the influence of sex and age on LV parameters and no ranges of normal have been reported using MASS® software. The aim of this study was to establish the ranges for normal LV volumes, mass and ejection fraction normalized to the influence of body surface area (BSA), age and sex from CMR in a large cohort of well-treated TM patients without myocardial iron overload.
Methods. Among the 923 TM patients who underwent CMR within the MIOT network for the assessment of cardiac iron overload, function and fibrosis, we selected 142 patients with no known risk factors or history of cardiac disease, normal electrocardiogram, no myocardial fibrosis and no myocardial iron overload (all the cardiac segments with a normal T2* value). All patients had been regularly transfused and chelated since early childhood. Moreover, we studied 71 healthy subjects matched for age and sex. LV function parameters were quantitatively evaluated in a standard way by SSFP cine images using MASS® software. LV end-diastolic volume, end-systolic volume, stroke volume, and mass were normalized to BSA (EDVI, ESVI, SVI, massI).
Results. The table shows the comparison of the CMR parameters with differentiation for sex and age in TM patients and healthy subjects and the cut-off of normality defined as mean – or + 2 standard deviation (SD). TM patients showed significantly lower BSA than the controls (P<0.0001). Significantly higher EDVI and SVI were found only for males < 14 years and > 30 years. Significantly higher LVEF were found only for males < 14 years. In TM patients all LV volumes indexes were significantly larger in males than in females (P<0.0001 in all cases). The EF was not different between the sexes. In males the ESVI and the EF were significant different among the age groups (P=0.006 and P=0.001, respectively). In females no significant differences were detected among the age groups.
<14 14–20 20–30 30–40 >=40 TM H P TM H P TM H P TM H P TM H P Males N=7 N=7 N=6 N=6 N=25 N=15 N=23 N=11 N=6 N=5 EDVI (ml/m2) 94 ± 18 (130) 75 ± 11 0.034 96 ± 20 (136) 91 ± 20 0.715 103 ± 17 (137) 101 ± 13 0.686 92 ± 15 (122) 80 ± 11 0.022 94 ± 9 (112) 75 ± 11 0.013 ESVI (ml/m2) 31 ± 6 (43) 24 ± 6 0.058 38 ± 8 (54) 35 ± 14 0.670 38 ± 8 (54) 39 ± 9 0.676 32 ± 6 (44) 29 ± 6 0.160 29 ± 6 (41) 28 ± 10 0.816 SVI (ml/m2) 63 ± 14 (91) 51 ± 7 0.050 57 ± 12 (81) 56 ± 8 0.868 65 ± 10 (85) 62 ± 9 0.433 59 ± 10 (79) 51 ± 10 0.027 64 ± 8 (80) 47 ± 8 0.007 Mass I (g/m2) 57 ± 7 (71) 68 ± 5 0.007 57 ± 13 (83) 71 ± 7 0.043 66 ± 12 (90) 77 ± 12 0.006 62 ± 12 (86) 66 ± 10 0.184 68 ± 16 (100) 74 ± 11 0.536 EF (%) 66 ± 4 (58) 54 ± 6 <0.0001 60 ± 2 (56) 66 ± 14 0.322 63 ± 3 (57) 62 ± 6 0.520 65 ± 3 (59) 65 ± 8 0.972 68 ± 6 (56) 62 ± 9 0.234 Females N=2 N=2 N=8 N=6 N=24 N=6 N=33 N=8 N=8 N=5 EDVI (ml/m2) 63 ± 8 (79) 62 ± 4 0.951 81 ± 8 (97) 80 ± 9 0.866 83 ± 16 (115) 78 ± 9 0.499 77 ± 11 (99) 79 ± 10 0.669 82 ± 19 (120) 77 ± 16 0.614 ESVI (ml/m2) 23 ± 1 (25) 22 ± 8 0.823 30 ± 6 (42) 31 ± 3 0.789 30 ± 8 (46) 30 ± 4 0.883 26 ± 6 (38) 29 ± 7 0.216 28 ± 8 (44) 28 ± 12 0.974 SVI (ml/m2) 40 ± 7 (54) 41 ± 4 0.919 49 ± 3 (55) 49 ± 6 0.892 53 ± 9 (71) 48 ± 6 0.234 51 ± 6 (63) 50 ± 8 0.915 54 ± 11 (76) 49 ± 6 0.394 Mass I (g/m2) 34 ± 3 (40) 59 ± 19 0.296 47 ± 8 (63) 56 ± 6 0.040 53 ± 9 (71) 54 ± 12 0.893 52 ± 9 (70) 55 ± 13 0.465 51 ± 12 (75) 56 ± 5 0.344 EF (%) 63 ± 3 (57) 46 ± 17 0.388 63 ± 4 (55) 62 ± 4 0.694 65 ± 5 (55) 62 ± 3 0.137 66 ± 5 (56) 63 ± 7 0.271 66 ± 4 (58) 63 ± 7 0.254
Conclusions. In a large cohort of well-treated TM patients significant differences in LV parameters compared to controls were limited to males < 14 years and > 30 years. Due to the influence of BSA, sex and age, appropriate “normal” reference ranges normalized these variables should be used to avoid misdiagnosis of cardiomiopathy in TM patients.

Disclosures:
No relevant conflicts of interest to declare.