We prospectively studied consecutive paediatric patients with LVNC at Texas Children's Hospital (Houston, Texas, USA) between January 1999 and May 2004. Standard transthoracic echocardiograms including TD analysis were obtaind for each patient. We compared children with LVNC with age‐ and sex‐matched normal controls during the study period (controls included children with a normal echocardiogram referred for echocardiography due to the presence of a cardiac murmur or abnormal screening chest x
ray or electrocardiogram). Diagnostic criteria for LVNC included (1) >3 trabeculations, (2) deep recesses and (3) a compacted: non‐compacted ratio >2:1.10
Comparisons were then drawn between patients with LVNC and an age‐ and sex‐matched normal control group, and subsequently between patients with LVNC who met the primary end points (PEPs) and secondary end points (SEPs) of the study. Study approval was obtained from the Internal Review Board at Baylor College of Medicine (Houston, Texas, USA). Consent was obtained from the patients or their family.
Study end points
The primary end point (PEP) of the study was defined as experiencing cardiac death or undergoing cardiac transplantation. The SEP was defined as developing congestive heart failure (CHF) requiring hospitalisation for medical management.
Demographic data including age at diagnosis, sex, presence of a positive family history and medical treatment were collected. Twenty‐four hour Holter monitors were reviewed to determine the incidence of a significant arrhythmia, defined as ventricular tachycardia. ECGs were reviewed and abnormalities documented.
All patients underwent a complete two‐dimensional, spectral Doppler and colour flow Doppler examination. Patients were examined in either a resting or a sedated state (infants and children <15 kg were sedated with 50–100 mg/kg of chloral hydrate). Examinations were performed using commercial ultrasound systems (Acuson Sequoia, Siemens Medical, Mountain View, California, USA) or Sonos 5500, Philips Medical Systems, Andover, Massachusetts). Echocardiograms were recorded either digitally or on a ½‐inch vertical helical scan video tape, and were subsequently analysed by use of either internal echocardiographic system software or directly from the stored digital images.
From the apical four‐chamber view, a pulsed Doppler sample volume was placed at the mitral valve annulus and subsequently at the leaflet tips, with five cardiac cycles recorded at each site during normal respiration. The cursor was placed between the LV outflow and the mitral inflow to record the isovolumic relaxation time (IVRT). Pulmonary venous inflow was measured from the right upper pulmonary vein using colour Doppler guidance. TD acquisition was set to pulsed‐wave mode (−30 to 30 cm/s), with gain adjusted to minimise the background noise. From the four‐chamber view, a 5 mm sample volume was placed at the lateral mitral annulus, septal annulus and lateral tricuspid annulus and 5–10 cycles were recorded.
A single observer blinded to the clinical outcome of patients performed the echocardiographic analysis (CJM). Two‐dimensional measurements including left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, left ventricular posterior wall and interventricular septal thickness were obtained using M‐mode and their respective z scores calculated.16
The left ventricular ejection fraction (LVEF) was determined using the Simpson's biplane method, including the ventricular volume between the LV trabeculations (fig 1).17
Mitral inflow Doppler signals were obtained at the mitral leaflet tips and analysed for the following: peak velocity of early (E) and late (A) filling, early deceleration time and the E/A ratio.18
IVRT was measured as described previously.18
The Tei index, defined as the sum of the isovolumetric contraction time and IVRT divided by LV ejection time, was calculated as reported previously.19
Pulmonary vein inflow was analysed for peak velocity and velocity time integral of systolic (S), diastolic (D) and atrial reversal waves (Ar).15
Systolic filling fraction (systolic velocity‐time integral/total forward flow velocity‐time integral) and the pulmonary Ar‐mitral A wave duration were calculated.20
From the TD tracings, the following measurements were made: early (Ea) and late (Aa) diastolic annular velocities, and systolic velocity (Sa).21
The lateral E/Ea and septal E/Ea were also calculated.
Figure 1Simpson's biplane method for determining left ventricular (LV) ejection fraction in patients with LV non‐compaction cardiomyopathy. (A) LV end diastolic volume. (B) LV end systolic volume.
Statistical analyses were performed using SAS statistical software V.8.2. Data were expressed as mean (SD) or median (25th–75th centile) based on whether they have a normal distribution or not. Continuous variables were estimated as mean (SD) and compared with use of Student's unpaired t test (χ2 test was used for categorical variables).
Event‐free survival was estimated by the Kaplan–Meier method, and differences were assessed by means of the log rank test. Multivariate Cox proportional hazards regression models were created using echocardiographic variables to determine predictors of the PEPs and SEPs. In the regression model for predictors, a forward stepwise programme was used to select covariates.22
The results were reported in terms of hazard ratios with 95% CI's. Multivariate logistic regression analysis and receiver operator characteristic (ROC) curves were used to analyse and display variables that might differentiate one group from another.23
A p value <0.05 was required for retention within the multivariate Cox regression model.