Study Participants

The study population consisted of 30 patients diagnosed before 2008 with NCCM by expert opinion (of whom 10 were included in a previous study on LV twist in NCCM) and 22 consecutive patients with prominent trabeculations (visual estimated end-systolic ratio of noncompacted to compacted layer >1.5) who underwent echocardiography in 2008, identified by one physician highly experienced with echocardiography (M.L.G.). All patients were in sinus rhythm and had good echocardiographic image quality that allowed for complete segmental assessment of LV rotation at both the basal and apical LV levels. During the enrollment of the 52 patients, 18 other patients (26%) were excluded because of suboptimal echocardiographic image quality not fulfilling this criterion. None of the patients had known coronary artery disease (excluded by coronary angiography), hypertension, or significant valvular heart disease. Patients were compared with 52 healthy age-matched and gender-matched control subjects without hypertension or diabetes and with normal left atrial dimensions, LV dimensions, and LV function. Furthermore, 15 patients with dilated cardiomyopathy (DCM) with LV volumes and ejection fractions comparable with those of the patients with NCCM were included as well. All subjects gave informed consent and the institutional review board approved the study.

Diagnostic Criteria for NCCM

Two methods were used to diagnose NCCM in the 52 patients. The first method was based on the echocardiographic diagnostic criteria for NCCM according to Jenni et al. : (1) a two-layered structure of the LV wall, with the end-systolic ratio of noncompacted to compacted layer >2 ( Figure 1 ); (2) finding this structure predominantly in the apical and midventricular areas; and (3) blood flow directly from the ventricular cavity into the deep intertrabecular recesses as assessed by Doppler echocardiography. The noncompacted-to-compacted ratio was quantitatively assessed, with the aid of electronic calipers, by one observer (M.L.G.) blinded to the results of LV twist and the expert opinion. In the second method, the diagnosis of NCCM was based on expert opinion. One clinical expert in NCCM diagnosis (K.C.) used, in addition to criteria of Jenni et al. , those of Finsterer and Stollberger, information on the history of the patient (including family history), and magnetic resonance imaging data but was also blinded to LV twist results. The 30 patients with previously established diagnoses of NCCM were revised according to these methods as well.

Example of echocardiographic short-axis images of both subjects with hypertrabeculation and patients with NCCM.

Echocardiography

Two-dimensional grayscale harmonic images were obtained in the left lateral decubitus position using a commercially available ultrasound system (iE33; Philips Medical Systems, Best, The Netherlands), equipped with a broadband (1-MHz to 5-MHz) S5-1 transducer (frequency transmitted, 1.7 MHz; frequency received, 3.4 MHz). All echocardiographic measurements were averaged from three heartbeats. Measurements of LV dimensions, volumes, fractional shortening, and ejection fraction were obtained in accordance with the recommendations of the American Society of Echocardiography. The LV was divided into nine segments to describe the location of noncompacted segments: one apical, four midventricular, and four basal segments (with an anterior, inferoseptal, anterolateral, and inferior segment each).

To optimize speckle-tracking echocardiography, images were obtained at a frame rate of 60 to 80 frames/s. Parasternal short-axis images at the LV basal level (showing the tips of the mitral valve leaflets) with the cross-section as circular as possible were obtained from the standard parasternal position, defined as the long-axis position in which the LV and aorta were most in line with the mitral valve tips in the middle of the sector. To obtain a short-axis image at the LV apical level (just proximal to the level with end-systolic LV luminal obliteration), the transducer was positioned one or two intercostal spaces more caudal, as previously described by us. From each short-axis image, three consecutive end-expiratory cardiac cycles were acquired and transferred to a QLAB workstation (Philips Medical Systems) for offline analysis.

Speckle-Tracking Analysis

Analysis of the data sets was performed using QLAB version 6.0, which was recently validated against magnetic resonance imaging for assessment of LV twist. To assess LV rotation, six tracking points were placed manually (after gain correction) on the midmyocardium on an end-diastolic frame in each parasternal short-axis image. In areas of hypertrabeculation, the tracking points were placed in the inner to midsection of the compacted part of the muscle. Tracking points were separated about 60° from one another and placed at 1 o’clock (30°, anteroseptal insertion into the LV of the right ventricle), 3 o’clock (90°), 5 o’clock (150°), 7 o’clock (210°), 9 o’clock (270°, inferoseptal insertion into the LV of the right ventricle), and 11 o’clock (330°) to fit the total LV circumference. After positioning the tracking points, the program tracked these points on a frame-by-frame basis using a least squares global affine transformation. The rotational component of this affine transformation was then used to generate rotational profiles.

Data were exported to a spreadsheet program (Excel; Microsoft Corporation, Redmond, WA) to determine LV peak systolic rotation during the isovolumic contraction phase (Rot _early ), LV peak systolic rotation during ejection (Rot _max ), and instantaneous LV peak systolic twist (Twist _max , defined as the maximal value of instantaneous apical systolic rotation − basal systolic rotation). Counterclockwise rotation and twist as viewed from the apex were expressed as a positive value, and clockwise rotation and twist were expressed as a negative value. End-systole was defined as the point of aortic valve closure. In the present study, different LV rotation patterns were recognized ( Figure 2 ):

• 1.
  

  Normal rotation

  
  
  
  
  • A.
    

    Completely normal rotation, characterized by initial counterclockwise and end-systolic clockwise basal rotation and initial clockwise and end-systolic counterclockwise apical rotation

    
    
  • B.
    

    Partly normal rotation, characterized by end-systolic clockwise basal rotation and end-systolic counterclockwise apical rotation but absence of either or both initial counterclockwise basal rotation or initial clockwise apical rotation

  
  
  
  
• 2.
  

  RBR

  
  
  
  
  • A.
    

    Clockwise RBR, characterized by clockwise basal and apical rotation throughout systole

    
    
  • B.
    

    Counterclockwise RBR, characterized by counterclockwise basal and apical rotation throughout systole

    
    
  • C.
    

    Initial clockwise followed by counterclockwise RBR

    
    
  • D.
    

    Initial counterclockwise followed by clockwise RBR

  
  

Schematic graphs of LV rotation patterns in healthy controls, subjects with hypertrabeculation, and patients with NCCM.

Statistical Analysis

Data are expressed as mean ± SD. Variables were compared using Student’s t tests or χ ² tests as appropriate. P values < .05 were considered statistically significant. Intraobserver and interobserver variability for LV twist were 5 ± 4% and 9 ± 4%, respectively, in line with our previous study of the feasibility of LV twist measurement using speckle-tracking echocardiography. To test the reproducibility of LV rotation patterns in the current study, speckle-tracking analysis was repeated by a different physician (F.K.) in all patients. There was 100% agreement on the observed LV rotation patterns.

Characteristics of the Study Population

Revision of the 30 patients with previously established diagnoses of NCCM led to confirmation of the diagnosis in 29 by the criteria of Jenni et al. and in all 30 by expert opinion. Of the 22 patients with various degrees of hypertrabeculation, seven were classified as having NCCM by the criteria of Jenni et al. and four by expert opinion. The remaining patients were classified as “subjects with hypertrabeculation.” So, in total, 36 patients were diagnosed as having NCCM by the criteria of Jenni et al. and 34 by expert opinion. In four patients, the expert diagnosis was discrepant from the criteria of Jenni et al. , on the basis of information about race, family history, LV function, and the results of magnetic resonance imaging. Clinical and conventional echocardiographic characteristics of the study population are shown in Table 1 .

LV Rotation and Twist in Normal Subjects and Patients With DCM

In all but one normal subject, initial counterclockwise rotation at the LV basal level and initial clockwise rotation at the LV apical level could be identified (basal Rot _early 2.0 ± 1.2°, and apical Rot _early −0.8 ± 0.6°, respectively). Furthermore, peak end-systolic rotation was always in a clockwise direction at the LV basal level and in a counterclockwise direction at the LV apical level (basal Rot _max −3.6 ± 1.8°, and apical Rot _max 7.2 ± 2.9°, respectively), leading to a Twist _max of 10.1 ± 2.3°. Although initial counterclockwise rotation at the LV basal level and initial clockwise rotation at the LV apical level were absent (LV rotation pattern 1B) in nine patients with DCM (60%) none of the patients with DCM showed RBR ( Table 2 ).

Table 2

LV rotation patterns in patients with NCCM, subjects with hypertrabeculation, patients with DCM, and controls

	Patients with NCCM		Subjects with hypertrabeculation
	Jenni et al. criteria	Expert opinion	Jenni et al. criteria	Expert opinion	Patients with DCM	Controls
Rotation pattern	( n = 36)	( n = 34)	( n = 16)	( n = 18)	( n = 15)	( n = 52)
Normal
1A	0	0	4	4	6	51
1B	6	4	8	10	9	1
Total	6	4	12	14	15	52
RBR
2A	13	13	1	1	0	0
2B	2	2	0	0	0	0
2C	1	1	1	1	0	0
2D	14	14	2	2	0	0
Total	30	30	4	4	0	0

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