Study population

From 1 March 2007 to 31 May 2011, all patients with SCA referred from the Reference Centre for Adult Sickle Cell Disease of Tenon Hospital to our echocardiography laboratory were eligible for inclusion. Patients who had developed acute chest syndrome, vaso-occlusive crisis or an acute complication within the previous 6 weeks (including fever, surgery, blood transfusion or hospital admission, whatever the reason) were excluded in order to focus on a group of stable patients free of confounding factors that could be linked to LA size. Other exclusion criteria were: more than mild mitral regurgitation, more than mild aortic stenosis, more than mild aortic insufficiency, any degree of mitral stenosis, valvular prosthesis, pregnancy, arteriovenous fistula and history of atrial arrhythmia (including atrial fibrillation, atrial flutter and other documented and/or treated atrial rhythm abnormality).

A total of 187 patients were considered for eligibility, of whom 60 did not meet the inclusion criteria. The remaining 127 patients constituted the study population. All of these patients were referred for routine evaluation of cardiac function and/or systematic screening for pulmonary artery hypertension.

Clinical data were obtained from a comprehensive review of each patient’s medical record. The diagnosis of SCA was based on molecular genetic techniques. All enrolled patients gave their consent to participate. The study was approved by the institutional committee on human research.

Echocardiography

Transthoracic echocardiography was performed by two experienced operators (N. Hammoudi, M. Djebbar) using the Vivid 7 system (GE Healthcare, Horten, Norway) or the iE33 system (Phillips Medical Systems, Andover, MA, USA). Images were transferred to a workstation equipped with Echopac PC software (GE Vingmed Ultrasound, Horten, Norway) for offline analysis. All examinations were analysed offline by two senior cardiologists (N. Hammoudi, M. Charbonnier) who were blinded to the clinical data. All projections were obtained according to the recommendations of the American Society of Echocardiography and measurements were averaged over three cardiac cycles.

From the M-mode, the following measurements were made at end-diastole: LV internal diameter and interventricular septal and posterior wall thicknesses. LV mass was derived and indexed to body surface area (LVMi); relative wall thickness was also calculated and LV remodelling was categorized as recommended . LV hypertrophy was defined as LVMi > 95 g/m ² in women and > 115 g/m ² in men. Further classification as either concentric hypertrophy (relative wall thickness > 0.42) or eccentric hypertrophy (relative wall thickness ≤ 0.42) was made .

From the two-dimensional mode, LA maximal volume was measured in all patients at the end of ventricular systole, just before opening of the mitral valve, using the area–length method from the apical four-chamber view, and indexed to body surface area . Since 2011, the LA apical two-chamber view has been acquired systematically and therefore biplane LA volume measurement was feasible in 24 patients. LA enlargement was defined as LAVi > 28 mL/m ² , and severe enlargement as LAVi > 40 mL/m ² . LV volumes and LVEF were measured using Simpson’s biplane method .

Using the pulsed-wave Doppler mode, LV outflow tract time–velocity integral, early and late peak diastolic velocities of the mitral (E and A) inflow and E-wave deceleration time were measured. LV output was calculated and indexed to body surface area as recommended . The peak e′ velocity was used to calculate the E/e′ ratio using pulsed tissue Doppler imaging of the septal mitral annulus .

Blinded to the LA volume measurements, the LV diastolic function profile was independently interpreted and categorized as normal or abnormal. DD was defined as an E/A ratio < 1 and/or deceleration time > 240 ms; E/A ratio ≥ 1 and E/e′ ratio > 10; E/A ratio > 95th percentile for age; or deceleration time < 140 ms and E/e′ > 10. This classification of LV diastolic function has a prognostic value for mortality in SCA . From continuous-wave Doppler, peak tricuspid regurgitation was recorded in multiple views and the highest level of velocity was selected.

Statistical analysis

All quantitative data are expressed as means ± standard deviations; qualitative data are expressed as counts and percentages. Comparisons between continuous patient data were made using the Mann–Whitney U test. The Chi-square test or Fisher’s exact test were used to compare categorical data, as appropriate. Pearson’s correlation test was used to analyse the univariate relations between variables. Stepwise multiple linear regression analysis was used to explore the independent predictors of LAVi; the variables included in the analysis were those associated with LAVi in univariate analysis, with a P value < 0.20.

Receiver operating characteristic (ROC) curves were plotted to determine the relevance of LAVi for predicting LVDD. In addition, using the Bland–Altman method, agreement between single-plane and biplane measurement of LAVi was assessed in the subgroup of patients in whom both apical four- and two-chamber views were acquired.

MedCalc Statistical Software, version 12.7.7 (MedCalc Software, Ostend, Belgium) was used for calculation. A P value < 0.05 indicated statistical significance.