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Methods and Techniques

Early Myocardial Deformation Changes Associated to Isolated Obesity: A Study Based on 3D-Wall Motion Tracking Analysis Adriana Saltijeral1, Leopoldo Pérez de Isla1, Olga Pérez-Rodríguez2, Santiago Rueda2, Covadonga Fernandez-Golfin1, Carlos Almeria1, Jose L. Rodrigo1, Willem Gorissen3, Juan Rementeria3, Pedro Marcos-Alberca1, Carlos Macaya1 and Jose Zamorano1 Obesity is considered as a strong risk factor for cardiovascular morbidity and mortality. 3D-wall motion tracking echocardiography (3D-WMT) provides information regarding different parameters of left ventricular (LV) myocardial deformation. Our aim was to assess the presence of early myocardial deformation abnormalities in nonselected obese children free from other cardiovascular risk factors. Thirty consecutive nonselected obese children and 42 healthy volunteer children were enrolled. None of them had any cardiovascular risk factor. Every subject underwent a 2D-echo examination and a 3D-WMT study. Mean age was 13.9 ± 2.56 and 13.25 ± 2.68 years in the nonobese and obese groups, respectively (59.7% and 40.3% male). Statistically significant differences were found for: interventricular septum thickness, LV posterior wall thickness, LV end-diastolic volume, LV end-systolic volume, left atrium volume, LV mass, and lateral annulus peak velocity. Regarding the results obtained by 3D-WMT assessment, all the evaluated parameters were statistically significantly different between the two groups. When the influence of obesity on the different echocardiographic variables was evaluated by means of multivariate logistic regression analysis, the strongest relationship with obesity was found for LV average circumferential strain (β-coefficient: 0.74; r2: 0.55; P: 0.003). Thus, obesity cardiomyopathy is associated not only with structural cardiac changes, but also with myocardial deformation changes. Furthermore, this association occurs as early as in the childhood and it is independent from any other cardiovascular risk factor. The most related parameter to obesity is LV circumferential strain. Obesity (2011) 19, 2268–2273. doi:10.1038/oby.2011.157

Introduction

The prevalence of overweight and obesity in children is increasing worldwide, becoming a global epidemic in both, children and adults (1). Obesity is considered as a strong risk factor for cardiovascular morbidity and mortality. Studies in adults have shown a relationship between obesity and structural and functional heart abnormalities. All these alterations are the socalled “obesity cardiomyopathy” (2). Nevertheless, the association between obesity and cardiovascular risk has been difficult to establish, because obesity is strongly associated with several cardiovascular risk factors. Thus, the study of the precise role of cardiac alterations related to obesity has been always based on statistical adjustments. Consequently, the role of obesity per se (isolated from its well-known adverse effects on plasma lipids concentrations, blood pressure, diabetes mellitus, etc.) has been controversial (3–6).

Left ventricular (LV) systole involves myocardial deformation: shortening in the longitudinal axis of the ventricle, a reduction of the inner diameter in the short axis and a rotational movement about the long axis. Myocardial volume is constant during the cardiac cycle. Thus, a myocardial segment of the LV will change in shape during systole: longitudinal and circumferential shortening (the so-called longitudinal and circumferential strain) and radial thickening (radial strain). But, deformation impairments may be “invisible” for the traditional imaging methods. It would be worth to use a tool able to detect subtle myocardial deformation impairments. 3D-wall motion tracking echocardiography (3D-WMT), which analyses myocardial motion by natural acoustic markers in the echocardiographic image, is a new technique that provides information regarding different parameters of LV myocardial deformation (7,8). This new method works in a fast and easy way as previously reported (8,9).

1 Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain; 2Pediatrics Department, Hospital Clínico San Carlos, Madrid, Spain; 3Toshiba Medical Systems Europe, Zoetemeer, The Netherlands. Correspondence: Leopoldo Pérez de Isla ([email protected])

Received 1 March 2011; accepted 24 April 2011; published online 30 June 2011. doi:10.1038/oby.2011.157 2268

VOLUME 19 NUMBER 11 | NOVEMBER 2011 | www.obesityjournal.org

articles Methods and Techniques Our aim was to assess the presence of early myocardial deformation abnormalities in nonselected obese children free from other cardiovascular risk factors. The rationale to enroll this population (children) was the need to study the precise effects of obesity on the heart, free from the confounding effect added by the presence of other concomitant risk factors. Methods and Procedures Study population This work was designed as a prospective study in which 30 consecutive nonselected obese children were enrolled between July and October 2009, from the patient population attending the obesity clinic for children of the Hospital Clínico San Carlos. Height and body weight were measured for each subject. BMI was calculated by using a dedicated formula (body weight in kilograms/body height in meters) (10) and BMI values were converted to standard deviation scores (BMISDS) adjusted for age and sex using the Spanish reference tables (11). Obesity was defined as having a BMI >2 s.d. above the median value. The control group consisted of 42 healthy volunteer children. Systolic blood pressure and diastolic blood pressure were measured by the cuff method. The presence of hypertension was established by the report of the second task force on blood pressure control in children (12). Hematological and biochemical variables were determined in the obese subjects from fasting blood samples. Hyperlipidemia was assessed by the American Academic of Pediatrics National Cholesterol Education Program recommendations (13). Exclusion criteria were the presence of any significant concomitant illness, treatment with any cardiovascular drug, any cardiovascular risk factor different from obesity, any cardiac disease, a very poor acoustic window and unwillingness of the patient. The Hospital Clinico San Carlos ethical review board approved the study. The participants and at least one of their parents or legal tutors provided written informed consent to be enrolled for the study. 2D and 3D echocardiography Every subject underwent a 2D-echo examination, including lateral mitral annulus tissue Doppler imaging (TDI) analysis, and a 3D-WMT study. The system used was an Artida system (Toshiba Medical Systems, Japan). A PST-30SBT 1-5 MHz phased array transducer was used for 2D and a PST-25SX 1-4 MHz matrix phased array transducer for 3D acquisitions. Temporal resolution was 17–22 volumes per second. The volume data was digitally stored. In-depth details regarding the acquisition and analysis process with this system have been published elsewhere (8) (Figure 1). All data were read in a blind way. Statistical analysis Statistical analysis was carried out using PASW (version 18.0; SPSS, Chicago, IL) and ENE (version 2.0; Departamento de Biometría de GlaxoSmithKline y el Servicio de Estadística de la Universidad Autónoma de Barcelona, Barcelona, Spain). Quantitative data were expressed as mean ± s.d. and qualitative data as absolute number (%). The minimum number of patients enrolled was calculated as follows: 80.00% power to detect differences by using a bilateral, two independent samples t-test; significance level: 5%; reference group assumed mean longitudinal strain −20.00%, experimental group −16.00% and both group s.d. 5%. The minimum estimated number of patients for each group was 26. Normal distribution was analyzed by Kolmogoroff– Smirnoff test. Comparisons between groups were made with Pearson’s χ2-test for categorical variables and the t-test for continuous variables. To evaluate the relative influence of obesity on the echocardiographic parameters that differed between obese and nonobese children, linear regression analysis was performed. Univariable linear regression models were constructed to analyze the associations of obesity with the dependent echocardiographic variables. Stepwise multivariable linear regression analysis was used to determine which determinants independently explain a significant fraction of the variance of obesity | VOLUME 19 NUMBER 11 | NOVEMBER 2011

40

−40 (%)

Figure 1  An example of 3D-wall motion tracking analysis display. Left ventricular endocardium and epicardium are semiautomatically detected and myocardial displacement is automatically analyzed.

Table 1  Patients’ clinical characteristics N Age (years) Gender (male)

Nonobese

Obese

42

30

13.90 ± 2.56

13.25 ± 2.68

0.30

43 (59.7%)

29 (40.3%)

0.66

P

Weight (kg)

48.94 ± 13.89

74.21 ± 20.98