Patient selection

Between January 2003 and January 2008, 16 consecutive patients for whom diagnosis of LVNC was suspected on echocardiographic criteria and without CMR contraindications were enrolled. Each patient was assessed clinically by echocardiography first and CMR studies were performed during the same week.

Among the 16 patients included, 12 fulfilled Jenni’s criteria . These specific echocardiographic diagnostic criteria are (in the absence of coexisting cardiac anomalies):

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  a typical two-layered myocardial structure with a thin compacted outer (epicardial) band and a much thicker, non-compacted inner (endocardial) layer consisting of trabecular meshing with deep endocardial spaces;

  
  
• •
  

  a maximum end-systolic non-compacted epicardial layer thickness/compacted epicardial layer thickness (NC/C) ratio >2;

  
  
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  colour Doppler evidence of deeply perfused intertrabecular recesses.

Four other patients were also included, despite having a maximum NC/C ratio ≤2. In these patients, LVNC was highly suspected due to the presence of a marked two-layered structure associated with more than three prominent trabeculations and a family history of LVNC.

This study complies with the declaration of Helsinki and was approved by our institutional review board. Written informed consent was obtained from all patients.

Two-dimensional echocardiographic imaging

Echo-2D were obtained using commercially available instruments (GE Medical Systems, Milwaukee, Wis) with 3.5-MHz transducers equipped with harmonic imaging. Images were acquired in the long-axis parasternal view, the three short-axis views (basal, mid, apical), and the 2-, 3- and 4-chamber apical views. These views were used to visualize all 17 segments according to American Heart Association recommendations . Offline analysis was then performed on digitally stored images (EchoPAC, GE Vingmed, Horthen, Norway).

CMR imaging

All imaging was performed on a 1.5-T MR scanner (Symphony TIM, Siemens, Erlangen, Germany with a 12-element phased array cardiac coil and Achieva, Philips, Best, The Netherlands with a 5-element phased array cardiac coil). Cine steady-state free precession sequences were acquired on long-axis, 2-chamber, 4-chamber and short-axis views to cover the whole left ventricle without any gap between images. For both scans, cine sequences with retrospective cardiac gating were used with the following parameters:

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  TR/TE = 40 ms/1.8 ms, slice thickness = 6 mm, no gap between slice, flip angle = 65°, matrix = 148 × 256, field of view = 350 mm × 350 mm, temporal resolution = 30 ms

  
  
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  TR/TE = 35/1.5 ms, slice thickness = 6 mm, no gap between slice, flip angle = 60°, matrix = 148 × 256, field of view = 350 mm × 350 mm, temporal resolution = 30 ms, for the Siemens and Philips scans, respectively.

All examinations were transferred to a dedicated workstation. LV volumes, ejection fraction and LV trabeculation were determined using Argus™ post-processing software (Siemens, Erlangen, Germany). The cine loops were reviewed and the end-diastolic and end-systolic frames were identified.

Image analysis

Qualitative and quantitative analyses of all 17 segments were performed using the three imaging methodologies: Echo-2D at end-diastole, Echo-2D at end-systole and CMR at end-diastole. CMR analysis was not performed at end-systole because, in most cases, the trabeculations and two-layered structure could not be visualized at this time in the cardiac cycle and because the measurements were validated at this point by a previous study. For each segment ( n = 272), the following criteria were assessed with the three imaging methodologies: analysable segment (yes/no), two-layered structure (yes/no) and NC/C maximum ratio. A segment was considered to be non-analysable if the imaging methodology failed to assess the presence or absence of the two-layered structure. The two-layered structure was assessed with one of the long- or short-axis views. The NC/C ratio was measured in short-axis views when possible, but long-axis views were used in some cases ( Fig. 1 ). Only segment 17 was always measured using 2- or 4-chamber views. For each patient and each imaging methodology, only the maximal NC/C ratio was used for subsequent analysis.

Assessment of the two-layered structure and the non-compacted epicardial layer thickness/compacted epicardial layer thickness (NC/C) ratio in short-axis views by the three imaging methodologies. Red lines are non-compacted layers; yellow lines are compacted layers. CMR: cardiac magnetic resonance; Echo-2D: two-dimensional echocardiography.

LV volumes and LV ejection fractions were calculated by Echo-2D from the 2- and 4-chamber images using the biplane Simpson’s rule and by CMR from the short-axis views using the disks method.

The same observer performed the entire analysis for each imaging methodology and was blinded to the data obtained for the alternative imaging test.

Pathological analysis

Pathological analysis was performed in the three patients who underwent cardiac transplantation. After perfusion and fixation of the hearts with formalin, the macroscopic preparations were analysed.

Statistical analysis

All continuous variables are expressed as means ± standard deviations; non-continuous variables are presented as percentages. Comparisons between non-continuous variables were performed by the χ ² -test. Comparisons of NC/C maximum ratios between the imaging methodologies (CMR at end-diastole, Echo-2D at end-diastole and Echo-2D at end-systole) were performed using a Friedman test and then, when significant, by the Wilcoxon rank sum test for post hoc analysis. In this case, to ensure an overall type I error rate of 5%, Bonferroni correction was applied and an adjusted p < 0.05/3 = 0.016 was considered significant.

Agreement in the NC/C maximum ratio between the imaging methodologies was determined by Bland-Altman analysis.

Two observers reviewed each imaging modality (Echo-2D and CMR) independently in all patients. The two observers were senior cardiologists who were experienced in echocardiography and CMR. All NC/C maximum ratio measurements were repeated by these two observers who were blinded to the previous results. The intraclass correlation coefficient and Bland-Altman analysis were used to assess the interobserver reproducibility for each imaging methodology. Bias was estimated by the mean difference between two measurements and paired t -tests were used to evaluate significance.

A two-sided p -value of <0.05 was established as the level of statistical significance for all tests. All analyses were performed with SPSS for Windows 15.0 (Chicago, IL, USA).

Patient characteristics

Our sample consisted of 16 consecutive patients aged 48 ± 17 years with LVNC. No patient had symptoms or signs of neuromuscular disease. Only one patient had LV thrombosis, which was identified by both CMR and Echo-2D. Patient characteristics are reported in Table 1 .

Table 1

Characteristics of the 16 patients with definite diagnosis or suspicion of left ventricular non-compaction.

Patient	Age (years)	Sex (M/F)	Family history	LBBB	NYHA class	LVEF (%) (Echo-2D)	LVEF (%) (CMR)	LVT
1	21	F	−	+	III/IV	65	36	−
2	22	F	−	+	I/II	42	45	−
3 a	29	M	−	−	I/II	44	59	−
4	38	F	+	−	III/IV	44	53	−
5	40	M	−	+	I/II	34	21	−
6	41	M	−	−	III/IV	43	34	−
7	42	M	+	+	III/IV	5	8	−
8	42	M	−	+	III/IV	65	63	−
9	45	M	−	+	I/II	20	32	+
10	50	M	+	+	III/IV	25	29	−
11	51	M	−	+	III/IV	18	18	−
12	54	M	+	+	III/IV	45	45	−
13	70	F	+	−	I/II	73	74	−
14 a	71	M	−	−	III/IV	27	27	−
15 a	72	M	+	−	I/II	44	10	−
16 a	74	F	−	+	III/IV	13	11	−

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