Regional Thicknesses and Thickening of Compacted and...

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Regional Thicknesses and Thickening of Compacted and Trabeculated Myocardial Layers of the Normal Left Ventricle Studied by Cardiovascular Magnetic Resonance Running Title: Dawson et al: Left Ventricular Trabeculation Dana K. Dawson, DM, MRCP, D.Phil, Senior Lecturer in Cardiovascular Medicine and Honorary Consultant Cardiologist, University of Aberdeen, Aberdeen, UK Alicia M. Maceira, MD, Consultant Cardiologist, ERESA-Cardiac Imaging Unit, Valencia, Spain Vimal J. Raj, MB BS, FRCR, Consultant Radiologist, Leicester Royal Infirmary, Leicester, UK Catriona Graham, MSc, BSc (hons), Lead Statistician at the Clinical Research Facility, Western General Hospital and University of Edinburgh, Edinburgh, UK Dudley J. Pennell, MD FRCP FACC FESC, Professor of Cardiology, National Heart and Lung Institute, Imperial College, London, UK Philip J. Kilner, MD, PhD, Consultant and Reader, Royal Brompton Hospital and the National Heart and Lung Institute, Imperial College, London, UK Correspondence to: Dana Dawson Royal Brompton Hospital Sydney Street London, SW3 6NP UK Tel: + 44 20 7352 8121 Fax: +44 20 7351 8816 E-mail: [email protected] Journal Subject Code: [30] MRI r Roy oy oy oy oy oy oyal al al l l al l I I I I I I Inf nf nf nf f f nfi i ir ir i i irma ma ma ma ma ma mary ry UK h h ern General Ho ital and Universit of Edinbur , Edinbu h, U nell, MD FRCP FACC FESC, Professor of Cardiology, National UK ham, MSc, BSc (hons), Lead Statis tician at the Clinical Research ern General Hospital and University of Edinburgh, Edinburgh, U nell, MD FRCP FACC FESC, Professor of Cardiology, National Lung Institute, Imperial College, London, UK by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from by guest on June 11, 2018 http://circimaging.ahajournals.org/ Downloaded from

Transcript of Regional Thicknesses and Thickening of Compacted and...

Regional Thicknesses and Thickening of Compacted and Trabeculated

Myocardial Layers of the Normal Left Ventricle Studied by

Cardiovascular Magnetic Resonance

Running Title: Dawson et al: Left Ventricular Trabeculation

Dana K. Dawson, DM, MRCP, D.Phil, Senior Lecturer in Cardiovascular Medicine and Honorary Consultant Cardiologist, University of Aberdeen, Aberdeen, UK

Alicia M. Maceira, MD, Consultant Cardiologist, ERESA-Cardiac Imaging Unit, Valencia, Spain

Vimal J. Raj, MB BS, FRCR, Consultant Radiologist, Leicester Royal Infirmary, Leicester, UK

Catriona Graham, MSc, BSc (hons), Lead Statistician at the Clinical Research Facility, Western General Hospital and University of Edinburgh, Edinburgh, UK

Dudley J. Pennell, MD FRCP FACC FESC, Professor of Cardiology, National Heart and Lung Institute, Imperial College, London, UK

Philip J. Kilner, MD, PhD, Consultant and Reader, Royal Brompton Hospital and the National Heart and Lung Institute, Imperial College, London, UK

Correspondence to: Dana Dawson Royal Brompton Hospital Sydney Street London, SW3 6NP UK Tel: + 44 20 7352 8121 Fax: +44 20 7351 8816 E-mail: [email protected]

Journal Subject Code: [30] MRI

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h hern General Ho ital and Universit of Edinbur , Edinbu h, U

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ham, MSc, BSc (hons), Lead Statistician at the Clinical Researchern General Hospital and University of Edinburgh, Edinburgh, U

nell, MD FRCP FACC FESC, Professor of Cardiology, NationalLung Institute, Imperial College, London, UK

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Abstract

Background We used cardiovascular magnetic resonance (CMR) to study normal left

ventricular (LV) trabeculation as a basis for differentiation from pathological non-

compaction.

Methods and Results The apparent end diastolic (ED) and end systolic (ES) thicknesses

and thickening of trabeculated and compact myocardial layers were measured in 120

volunteers using a consistent selection of basal, mid and apical CMR short axis slices. All

had a visible trabeculated layer in one or more segments. The compact, but not the

trabeculated layer, was thicker in males than females (p<0.01 at ED and ES). When plotted

against age, the trabeculated and compact layer thicknesses demonstrated opposite changes:

increase of the compact layer after the fourth decade at both ED and ES (p<0.05), but a

decrease of the trabeculated layer. There was age-related preservation of total wall thickness

at ED but increase at ES (p<0.05). The compact layer thickened whereas the trabeculated

layer thinned with systole but neither change differed between sexes. With age, the most

trabeculated LV segments showed significantly greater systolic thinning of trabeculated

layers and conversely, greater thickening of the compact segments (p<0.05). Total wall

thickening is neither gender nor age-dependent. There were no gender differences in the

trabeculated/compact ratio at ES or ED, but the ES trabeculated/compact ratio was smaller in

older (50-79 years) versus younger groups (20-49 years), p<0.05.

Conclusions We demonstrated age and sex-related morphometric differences in the

apparent trabeculated and compact layer thicknesses, and systolic thinning of the visible

trabeculated layer that contrasts with compact myocardial wall thickening.

Key Words: trabeculae, myocardium, systolic thickening, non-compaction, contractility

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ompact layer after the fourth decade at both ED and ES (p(( <0.05)

rabeculated layer. There was age-related preservation of total wa

se at ES (p(( <0.05). The compact layer thickened whereas the trab

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Comparisons of heart structure between the classes of living vertebrates together with studies

of mammalian cardiogenesis suggest that a spongy, non-compact structure is the fundamental

state of vertebrate ventricular myocardium. The process of compaction is an acquired

characteristic in reptiles, birds and mammals. In human embryonic development, a compact

layer of myocardium appears and gains in relative thickness between the 6th and 12th week, as

ventricular septation is completed1. However, endocardial appearances on imaging or at post

mortem inspection2 show that mature human ventricles typically retain variable degrees of

endocardial trabeculation3 with structural and mechanical properties that differ from those of

the compact layer4, and with considerable further variation between ventricular regions. This

makes the definition of criteria for pathological left ventricular non-compaction (LVNC)

challenging and controversial5. As the current phenotypic definition of LVNC relies on the

ratio of Trabeculated/Compacted myocardium, it is essential to have a detailed description of

this ratio, and its variability, in the normal phenotype. In the current study, we used routine

Cardiovascular Magnetic Resonance (CMR) - to visualize the segmental incidence,

thicknesses and thickening of the visible trabeculated and compacted myocardial layers in a

prospectively recruited cohort of healthy volunteers.

Methods

a. Subjects: We recruited 120 normal volunteers (10 males, 10 females in 6 decile groups

between 20-80 years old). The baseline characteristics of this cohort has been previously

published6. The study was approved by the Royal Brompton Local Research Ethics

Committee and all subjects gave informed consent.

b. Imaging: All subjects underwent CMR imaging on a 1.5 T Siemens Sonata system. After

localizers, three long axis views and a complete short axis stack of balanced steady state free

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variability, in the normal phenotype. In the current study, we us

M netic Resonance (CMR) - to visualize the s mental incidenc

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ated/Compacted myocardium, it is essential to have a detailed d

variability, in the normal phenotype. In the current study, we us

Magnetic Resonance (CMR) - to visualize the segmental incidenc

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precession cine images were acquired. Sequence parameters included repetition time 3.2ms,

echo time 1.6ms, slice thickness 7mm, inter-slice gap 3mm, in-plane pixel size 2.1x1.3 mm,

flip angle 60 . Acquired pixels were routinely interpolated by the CMR system software

during image reconstruction.

c. Data analysis was performed in CMRTools (Imperial College, London). A consistent

selection of 3 designated short axis slices was applied throughout: the ‘basal’ slice measured

was 2 cm down from the most basal short axis slice, located on the ventricular side of the

atrio-ventricular junctions of both ventricles at end-diastole. The ‘apical’ slice was 2 cm up

from the most apical slice showing LV myocardium. The mid LV slice was equidistant in

between. Manual measurements of the apparent end-diastolic (ED) and end-systolic (ES)

thicknesses of the trabeculated and compacted layers in 16 of the standard 17 segments7,

excluding the true apex, were made for each subject. A schematic presentation of the

selection of slices corresponding to the basal, mid-ventricular and apical short axis,

myocardial segmentation and assignment to walls is presented in Figure 1a. The boundary

between compact and trabecular myocardium was chosen for each segment as the line outside

which no trabeculations were apparent (Figure 1b). Review in cine mode can help locate this

boundary (Movie 1). As the trabecular layer could only rarely be described as having a

uniform thickness in a particular segment, its thickness was measured from this boundary to

the peak of the most prominent trabeculae in each segment. Measurements were performed

by two independent, experienced observers for 6 patients to derive inter- and intra-observer

variability. Wall thickening was calculated separately for the trabecular and the compacted

layers and also for the total LV wall thickness by expressing the systolic increase of each

apparent thickness as a percentage of its apparent ED thickness.

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e apex, were made for each subject. A schematic presentation f

s corresponding to the basal, mid-ventricular and apical short ax

mentation and assignment to walls is presented in Figure 1a The

e trabeculated and compacted layers in 16 of the standard 17 seg

e apex, were made for each subject. A schematic presentation of

s corresponding to the basal, mid-ventricular and apical short ax

mentation and assignment to walls is presented in Figure 1a The

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Statistical analysis was performed in MiniTab 15. Descriptive statistics are expressed as

mean±SD (or SEM) if normally distributed and as median (first, third quartile) if non-

parametric. 2 sample t-test, Mann Whitney, one way-ANOVA and Kruskall-Wallis tests were

used appropriately for parametric or non-parametrically distributed variables to determine

any differences with gender or age groups for each myocardial segment. Where analyses of

variance were significant, linear regression was also employed in order to confirm trends.

Variabilities were calculated as the difference divided by the mean of the two independently

measured variables, expressed as mean SD. Results were considered significant with a p

value <0.05.

Results

Segmental incidence of trabeculae

Figure 1 shows the incidence of an apparent trabecular layer in each segment at ED and ES.

A trabecular layer was visible in one or more segments in all 120 volunteers. Trabeculae were

prevalent in anterior and lateral segments at apical and mid-cavity levels, but usually absent

from septal segments. The apical lateral wall was the most commonly trabeculated territory,

followed by the mid and apical anterior wall, mid ventricular lateral wall and less so by the

inferior wall. No gender or age specific characteristic differences of trabecular distribution

were identified. Trabeculae were consistently more apparent at ED compared to ES. The

intra- and inter-observer variabilities are shown in Table 1.

Trabecular and Compacted layers thicknesses and their variation with gender and age

e

he incidence of an apparent trabecular layer in each segment at E

ence of trabeculae

he incidence of an apparent trabecular layer in each segment at E

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Table 2 presents the mean individual thicknesses of the trabecular and compact layers as well

as the full segmental wall thickness at ED and ES. The apical free wall was the only segment

where the average trabeculated layer exceeded the compact layer thickness, and only at ED.

There were significant gender differences when the thickness of the compacted layer was

compared, at both ES and ED (p<0.05 for all segments), but no gender differences were

found in trabecular layer thickness (p=ns). There were corresponding differences between

males and females in the total myocardial layer thickness, for both phases of the cardiac cycle

(p<0.05 for all segments) - Tables 3 and 4 in the Data Supplement.

Figure 2 shows a representative age-related change of thickness of the compacted and

trabecular layers at ED (shown here for the anterior wall segments) and Figure 3 illustrates

corresponding findings at ES in the lateral wall. For all compacted myocardial segments the

pattern was similar, with a relatively higher thickness in the third decade of life, followed by

a slight decrease in thickness during the fourth decade and then progressive increase in each

age decile. The differences across age groups in the compact layer thickness measured at both

ED and ES were significant (p<0.05 for all segments). Age-related differences were also

found in the trabecular layer thickness with an opposite pattern of change compared to the

compacted layer, but these differences did not reach significance for all examined segments

(p<0.05 for segments 1, 7, 13, 16 at ED and p<0.05 for segments 1, 5, 6, 12, at ES, the

remaining segments demonstrating only a trend but p=ns).

The age group-related changes in the compacted and trabecular layers contributed to a small,

progressive increase in the total wall thickness measured at ES across age groups (p<0.05 for

all segments) but this difference was no longer apparent across all ED measurements (p<0.05

only for segments 1,7,13 and 16, p=ns for all the rest). Figure 4 demonstrates the ES and ED

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ndings at ES in the lateral wall. For all compacted myocardial se

ar, with a relatively higher thickness in the third decade of life,

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ndings at ES in the lateral wall. For all compacted myocardial se

ar, with a relatively higher thickness in the third decade of life,

in thickness during the fourth decade and then progressive incre

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total wall thickness changes with age [shown for the anterior (4A) and lateral wall (4B)

segments].

Changes of the Trabecular and Compacted layers during systolic contraction and patterns

of these changes with age

The apparent compact layer thickened relatively uniformly, by an average of 73±13%. In

contrast, the visible trabecular layer became thinner, generally making a negative

contribution to total radial thickening, which averaged 52±13% (individual segment analysis

shown in Table 2).

Neither the trabecular layer thinning nor the compact layer or total wall thickening were

different between sexes in any segment (p=ns) – Table 5, Data Supplement.

As regarding an age-related pattern in systolic changes, there were no significant differences

in thickening across age groups for the total myocardial layer (p=ns for all segments).

However, when the two components (trabecular and compacted layers) were examined

separately, once again an opposite pattern of change was observed. Figure 5 illustrates how

the systolic thinning of the trabecular layer was progressively greater with age (statistically

significant for segments 1, 6, 7, 11, 12, 15, 16, p<0.05, whereas the remaining segments

demonstrated only a trend in the same direction, p=ns). Conversely, as shown in Figure 5, the

systolic thickening of the compact layer was also progressively greater with age (statistically

significant for segments 1, 6, 7, 11, 12, 15, 16, p<0.05, the remaining segments

demonstrating only a trend which did not reach statistical significance). The segments where

the age-related patterns of thickening/thinning were significant were the most trabeculated

segments.

The trabecular/compacted layer ratio and its changes with cardiac cycle and age

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the two components (trabecular and compacted layers) were exa

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age-related pattern in systolic changes, thaa ere were no significant

oss age groups for the total myocardial layer (p(( =ns for all segme

the two components (trabecular and compacted layers) were exa

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The ratio between the apparent trabecular and compacted layers changed markedly through

systole and diastole. At ED, the ratio was < 1 in all segments but the apical free wall. Of

note, 64% of the normal volunteers had an apical free wall trabecular layer at least as thick as

the compacted layer, 4 volunteers had an ED trabecular/compacted ratio higher than 2, one

being higher than 2.3 (the highest trabecular/compacted ratio recorded in the cohort across all

segments was 3) – see Table 2. At ES, the ratio was <0.5 in all segments with the exception

of the apical free wall. Figure 6a shows the trabecular/compacted ratio for all segments.

There were no gender differences when the trabecular/compacted ratio was compared, either

at ES or ED – data in Tables 3 and 4, Data Supplement. There were no age-related trends in

the trabecular/compacted ratio at ED (p=ns, graphs not shown). However, the

trabecular/compacted ratio at ES was significantly smaller in the older groups (50-79 years)

versus the younger groups (20-49 years), p<0.05 for all trabeculated segments – as shown in

Figure 6b.

Papillary muscles and false tendons

Papillary muscle heads were seen during both diastole and systole (minimum-maximum

number of heads for the antero-lateral and postero-medial respectively): at basal level 0-4/0-

3, mid-ventricular level 0-4/0-5 and at apical level 0-4/0-3. There were 14 false tendons, most

of them located at basal LV level and in the anterior wall.

Discussion

In this study we use CMR to determine the segmental incidence of a trabeculated layer and

the apparent thickness and thickening of the trabecular, compacted and total myocardial

layers of the LVs of a prospectively recruited cohort of healthy volunteers. The main and

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er groups (20-49 years), p<0.05 for all trabeculated segments –

es and false tendons

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novel findings of this study are: 1) the prevalence and extent of trabeculated subendocardial

regions in healthy individuals, 2) the apparent systolic thinning of the trabeculated layer in

contrast to the marked thickening of the compact layer during contraction, and 3) specific

age- and gender-related differences in the absolute and proportional thicknesses of these

layers at ES and ED.

We chose to make linear measurements in routine short axis CMR cines for several reasons:

This approach is practical for retrospective analysis of routinely acquired CMR studies, it

lends itself to segmental analysis, and the measurements can be compared directly with

previously proposed echocardiographic criteria for LVNC2,8. We also believe that the short

axis slices orientation is preferable to long axis for technical reasons: as the orientations of

LV trabeculations tend to be predominantly longitudinal, CMR short axis cines seemed more

suitable for distinguishing the trabeculated from the compacted layers than long axis cines, as

studied previously9. Due to the elongated shape of voxels constituting a cine image, short

axis images should be less prone to blurring of boundaries due to partial volume averaging10.

However, disadvantages of short axis slices include systolic through-plane myocardial

movement, particularly relative to the basal slices, and the varying number of slices needed to

cover ventricles of different sizes. For the latter reason, a consistent approach of slice

selection was applied, regardless of ventricular size.

The compact myocardial layer was consistently thicker across all segments in males

compared to females and this relative difference was maintained throughout the cardiac

cycle. The compact myocardial layer was slightly thicker during the third decade of life, a

slight decrease in thickness was observed during the fourth decade, after which it

progressively increased until the eighth decade. These patterns suggestive of exercise

conditioning/deconditioning at identical time-points were also suggested by the Framingham

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nguishing the trabeculated from the compacted layers than long a

ly9. Due to the elongated shape of voxels constituting a cine ima

uld be less prone to blurring of boundaries due to partial volume

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cohort analysis11. The trabecular layer measurements showed an opposite trend for change

with age. As it is unlikely that trabeculae would continue to compact in adult life, the obvious

explanation of our results is that these changes are due to age-related trabecular physiologic

hypertrophy. Because of hypertrophy, the interstices between the more epicardial trabeculae

may become excluded, this region then appearing and being measured as compacted.

However, no significant changes in the total myocardial layer thickness at ED were detected

with increasing age, which suggests that the true compact layer may remain relatively

unchanged over time. These results are consistent with our previous results6 and with those of

others12 who found no change with age in total LV mass measured from ED frames. These

findings can also be reconciled with previous Echocardiography studies which used LV wall

thicknesses to derive changes in LV mass over time and concluded that there was a temporal

increase in LV mass with age13,14. Due to the narrow ultrasound beam thickness (< 5mm) and

noise, fine structures of various curvature and orientation such as trabeculations are less well

resolved by the spatial resolution of trans-thoracic 2D-Echocardiography and it is most likely

that the perceived endocardial border on native echocardiography images was equivalent to

our interpretation of apparent compact layer boundary. This is supported by the finding of

larger ED volumes when LV opacification contrast agents were used versus smaller ED

volumes resulting from native echocardiography images15. The age-related hypertrophy of

the trabecular layer after the fourth decade translating into a progressively thicker effective

compact layer may be a necessary adaptation to maintain a constant myocardial wall stress,

consistent with previously described age-related increases in both systolic and diastolic blood

pressure after the fourth decade in healthy volunteers16. The concept of trabecular layer

hypertrophy as a physiological phenomenon and the bi-phasic pattern of this hypertrophy has

not been known to date.

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mass with age13,14. Due to the narrow ultrasound beam thickness (

ures of various curvature and orientation such as trabeculations a

patial resolution of trans-thoracic 2D-Echocardiography and it i

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With the systolic thickening and approximation of individual trabeculations, the apparent

boundary between trabecular and compact layers may shift relative to actual myocardial

structures as visible interstices are eliminated. Part of the diastolic trabeculated layer may

thus appear compact at end systole. This would account in part for the apparent systolic

thinning of the trabeculated layer, and the relatively high measurements made from CMR

cine images of the apparent thickening of the compact layer, which exceeded previously

reported measurements of axially directed strain based on CMR myocardial tagging17. The

subendocardial myocytes are predominantly longitudinally orientated. They must,

individually, thicken in cross section as they contract if they maintain their volume, in spite

of the fact that the endocardial circumference is forced by the contraction of the more

circularly oriented mid-myocardial layers to diminish in systole18. This points to the

potential mechanical advantage, in the endocardium, of a trabeculated rather than compact

myocardial structure. With interstices between, not only the systolic thickening of myocytes,

but also the circumferential shortening of the endocardium can be accommodated by the

exclusion of intervening blood.

This interpretation is potentially relevant to the issue of diagnosing pathological LVNC in the

presence of dilated cardiomyopathy19. An abnormally high trabeculated relative to compact

myocardial layer thickness may, at least in part, be a result and not necessarily a cause of

dilatation. The global stretching of the dilated ventricular wall is likely to be associated with

greater than normal separation of the trabeculations, from one another and possibly from the

abnormally thin compact myocardial layer. Furthermore, the excessive wall tension relative

to trans-mural pressure of a dilated heart tends, according to LaPlace’s law, to result in

pathologic hypertrophy, presumably of trabecular as well as compact myocardium. These

effects would shift the ratio of visibly trabeculated to compact myocardial thickness towards

the apparently non-compacted in any cardiomyopathy that results in global dilatation.

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Finally, there were no significant changes either related to gender or age when the ratio of

trabecular/compacted myocardium was examined at ED. Importantly, a ratio less than 1 in all

segments except the apical lateral wall appears to characterize the human volunteer cohort –

this may have important implications in defining segmental LVNC. The

trabecular/compacted ratio was significantly greater at ES in the young age groups compared

to the older ones; this may have implications for the choice of cardiac phase2,8,9 for

discriminating normal from non-compacted LVs. The differentiation may be easier in

segments with abundant rather than sparse trabecular preservation.

Study limitations: Cardiac CT could have offered better spatial resolution and isotropic

voxel size compared to CMR. However, even with modern protocols, the radiation dose

involved could not be justified in the case of volunteers. Due to the same spatial resolution

constraints we could not include segment 17 in our analysis.

Conclusions: These results give novel insight into the prevalence, segmental distribution,

dynamics and likely functional role of a trabecular myocardial layer. We demonstrate for the

first time age and sex related morphometric differences in the apparent trabecular and

compact layer thicknesses which in turn contribute differently to the total wall thickening.

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Sources of Funding

Dr. Dana Dawson was the recipient of the van Geest Advanced Imaging Fellowship (UK). Dr.

Philip Kilner is supported by the British Heart Foundation. The study was supported by the

National Institutes of Health Research Cardiovascular Biomedical Research Unit at the Royal

Brompton and Harefield NHS Foundation Trust and Imperial College.

Disclosures

None.

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References

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pphahahhhh neneeeeee, , ,,,, AlAlAlAlAlAlAl-SSaaaaaaaaaadididididididi,,,,, , , NN

ald, anananananananddddddd VaVaVaVaVaVaVanononononononovevevevevevv rs

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Table 1. Intra- and inter-observer variability (expressed as ratio between the difference and

the mean of two independent readings). Data is presented as mean SD.

Intra-observer variability Inter-observer variability

Trabecular layer (Diastole) 0.10 0.19 0.10 0.17

Trabecular layer (Systole) 0.02 0.05 0.05 0.08

Compact layer (Diastole) 0.004 0.006 0.05 0.11

Compact layer (Systole) 0.02 0.08 0.02 0.09

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Table 2. Thicknesses of trabecular, compact and total myocardial layers at ED and ES and thickening of trabecular, compact and total

myocardial layers. Data are presented as mean±SD for normally distributed variables and as median (first, third interquartile ranges) for non-

parametric variables. Figures in square brackets represent the highest ratio measured in each segment.

End-diastole End-systole Wall thickening

(ES-ED)x100/ED

Segment

Thickness of

trabecular

layer (mm)

Thickness of

compacted

layer (mm)

Total wall

thickness

in diastole

(mm)

Trabecular/

Compacted

ratio

[max ratio]

Thickness of

trabecular

layer (mm)

Thickness of

compacted

layer (mm)

Total wall

thickness

in systole

(mm)

Trabecular/

Compacted

ratio

[max ratio]

Trabecular

layer (%)

(Minus

implies

thinning)

Compacted

layer (%)

Total

layer

(%)

1 3.0 (0,4.6) 7.9±1.9 10.6±3.4 0.380±0.036

[1.6]

0 13.7±3.0 14.5±3.0 0.078±0.017

[0.9]

-30±10 72±13 43±13

2 0 9.6±2.5 9.6±2.5 0 0 14.0±2.8 14.0±2.8 0 49±12 46±12

3 0 8.7±2.0 8.6±2.0 0 0 11.7±2.4 11.7±2.4 0 34±12 31±13

4 0 7.7±1.7 8.0±2.1 0.059±0.018 0 13.1±2.5 13.2±2.7 0.019±0.007 -45±20 71±13 62±13

ratio layer (mm) layer (mm) in systo

Trabecular/

Compacted

ratio

Thickness of

trabecular

layer (mm)

Thickness of

compacted

layer (mm)

Total w

thickne

in systo

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[1] [0.4]

5 0 (0,3.9) 7.0±1.6 8.9±2.4 0.318±0.044

[1.8]

0 13.0±2.5 13.6±2.4 0.060±0.013

[0.6]

-30±40 83±13 61±13

6 0 (0,4.1) 7.0±1.4 9.0±2.5 0.289±0.034

[1.3]

0 12.7±2.6 13.2±2.3 0.061±0.015

[1]

-20±40 77±13 56±13

7 5.6±2.8 6.6±1.5 12.3±3.5 0.879±0.043

[2.2]

4.5±2.1 11.4±3.0 15.9±3.4 0.443±0.028

[1.7]

-20±40 75±13 34±12

8 0 7.9±1.6 8.4±1.9 0.080±0.025

[1.4]

0 12.9±2.9 13.3±2.8 0.046±0.015

[1.1]

-5±1 65±12 61±13

9 0 8.1±1.5 8.1±1.5 0 0 12.9±2.3 12.9±2.3 0 60±12 58±13

10 0 (0,2.1) 7.1±1.4 8.4±2.4 0.203±0.035

[1.6]

0 12.3±2.9 13.2±3.1 0.088±0.018

[0.8]

-10±30 74±12 61±13

11 4.2±2.5 6.3±1.4 10.5±2.9 0.704±0.044

[1.8]

3.1±2.5 11.7±3.1 14.8±3.4 0.298±0.026

[1]

-26±40 87±13 84±15

12 4.4±2.7 6.3±1.4 10.7±2.9 0.756±0.048

[2.4]

2.8±2.1 11.3±2.8 14.1±2.9 0.287±0.024

[1]

-35±40 83±14 36±14

3.0 15.9±±±±±±±3333333

[2.2]

0

[2.2]

0.080±0.025

[1.4]

0 12.9±2.9 13.3±2

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13 5.6±2.7 6.4±1.4 12.0±3.0 0.914±0.045

[2.2]

4.2±2.1 11.6±2.2 15.8±2.9 0.386±0.023

[1]

-16±40 87±13 36±12

14 0 7.3±1.7 8.0±2.5 0.112±0.031

[1.8]

0 12.7±2.4 13.1±2.4 0.046±0.014

[1]

-31±12 76±13 69±14

15 0 (0,4.5) 6.1±1.4 8.3±2.6 0.395±0.046

[1.8]

0 (0,3.6) 11.4±3.0 12.9±2.8 0.167±0.025

[0.8]

-32±30 85±13 63±14

16 7.1±2.4 6.1±1.3 13.2±3.3 1.190±0.042

[3]

5.0±2.3 11.2±2.7 16.3±3.1 0.493±0.025

[1.5]

-24±30 85±13 26±13

Average

all

segments

7.4±1.5 9.7±2.5 12.4±2.7 14.0±2.6 -24±19 73±13 52±13

2 7 11111116666666 3±3±3±3±3±3±3±33331.190 0.042 5.0 2.3 11.2 2.7 16.3 3

12.4±2.7 14.0±2.

1.190 0.042

[3]

5.0 2.3 11.2 2.7 16.3 3

12.4±2.7 14.0±2.

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Figure Legends

Figure 1: (a) The systematic selection of basal, mid-cavity and apical slices chosen for

measurements of trabecular and compact layer thickness is shown. The segmental incidence

of apparent trabeculae seen at both ED and ES is indicated as percentages in white for each of

the 16 segments. The dotted line indicates the ES location of the mitral valve. (b) Examples

of ED and ES frames showing the boundaries (white dotted lines) of the trabeculated layer

(red arrows) and compacted layer (blue arrows).

Figure 2: Compacted and trabecular layer thicknesses at ED per age groups (anterior wall).

Data is plotted as mean SEM with the exception of the first data point representing the

trabecular layer thickness in the 20-29 age group on Segment 1,which is shown as median

(first and third quartiles are 0, 4.6). and † = p<0.05 across age groups of the compact and

trabecular layer, respectively.

Figure 3: Compacted and trabecular layer thicknesses at ES per age groups (lateral wall).

Data is plotted as mean SEM. and † = p<0.05 across age groups of the compact and

trabecular layer, respectively.

Figure 4: (a) Total myocardial wall thickness (anterior wall) at ED and ES per age groups;

(b) Total myocardial wall thickness (lateral wall) at ED and ES per age groups. Data is

plotted as mean SEM. and † = p<0.05 across age groups of the total myocardial layer at ES

and ED, respectively.

Figure 5: Systolic trabecular layer thinning and compacted layer thickening shown as a

pattern with age, in the most trabeculated LV segments. Data is plotted as mean SEM. and

† = p<0.05 across age groups of the compact and trabecular layer, respectively.

a poioioioioioiointntntntntntnt r rrr rrrepepepepepepeprererererereresesesesesesesentntntntntntntiiiiiii

h a

u m

r

hickness in the 20-29 age group on Segment 1,which is shown a

uartiles are 0, 4.6). and † = p<0.05 across age groups of the com

respectively.

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Figure 6: (a) Trabecular/Compact ratio at ED (red) and ES (blue) in each segment; (b)

Trabecular/Compact ratio at ES in younger versus older patients in all 16 segments. Data is

plotted as mean SEM. = p<0.05 in young versus old age group for each plotted segment.

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1

4

2

3 5

6

7

8

9

10

11

12

13

14

15

16

SeptumAnterior wall

Inferior wallLateral wall

b

a

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= trabecular layer• = compact layer

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

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40-4

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50-5

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60-6

9

70-7

9

Age group

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= trabecular layer• = compact layer

† †

Age group

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

Age group

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Age group

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

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50-5

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70-7

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= total wall thickness at end-diastole= total wall thickness at end-systole

Age group

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

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70-7

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20-2

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40-4

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60-6

9

70-7

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20-2

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30-3

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40-4

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50-5

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60-6

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70-7

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70-7

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Age group

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= trabecular layer• = compact layer

† †

† †

† †

20-2

9

30-3

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40-4

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50-5

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70-7

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20-2

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60-6

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70-7

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20-2

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50-5

9

60-6

9

70-7

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20-2

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30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

Age group

Age group

49

2200-2

9

30-3

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60-6

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70-7

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a b

= trabecular layer• = compact layer

SegmentWall

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KilnerDana K. Dawson, Alicia M. Maceira, Vimal J. Raj, Catriona Graham, Dudley J. Pennell and Philip J.

the Normal Left Ventricle Studied by Cardiovascular Magnetic ResonanceRegional Thicknesses and Thickening of Compacted and Trabeculated Myocardial Layers of

Print ISSN: 1941-9651. Online ISSN: 1942-0080 Copyright © 2010 American Heart Association, Inc. All rights reserved.

TX 75231is published by the American Heart Association, 7272 Greenville Avenue, Dallas,Circulation: Cardiovascular Imaging

published online December 30, 2010;Circ Cardiovasc Imaging. 

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SUPPLEMENTAL MATERIAL

Table 3 - ED thicknesses of trabeculated, compacted and total layer and trabeculated/compacted ratio in female and male subjects

(Data is presented as mean±SEM) Trab = trabecular, C = compacted, F = female, M = male, na=not applicable, 0∗=measurement <0.01,

thus, not of clinical utility.

Segment Trabeculated p Compacted p Total layer p Trab/C ratio p

F M F M F M F M

1 2.5±0.3 3.1±0.3 0.29 7.1±0.2 8.6±0.2 <0.01 9.5±0.4 11.7±0.4 <0.01 0.3±0.0 0.3±0.0 0.92

2 0.1±0.1 0 0.38 8.6±0.3 10.5±0.3 <0.01 8.6±0.3 10.5±0.3 <0.01 0∗ 0∗ 0.33

3 0 0 na 7.8±0.2 9.6±0.2 <0.01 7.8±0.2 9.6±0.2 <0.01 0 0 na

4 0.3±0.1 0.4±0.1 0.54 6.9±0.2 8.5±0.2 <0.01 7.0±0.2 8.9±0.2 <0.01 0∗ 0∗ 0.97

5 1.9±0.3 1.8±0.3 0.79 6.3±0.2 7.7±0.2 <0.01 8.2±0.3 9.5±0.3 <0.01 0.3±0.0 0.2±0.0 0.22

6 1.9±0.3 1.9±0.3 0.91 6.3±0.1 7.7±0.2 <0.01 8.2±0.3 9.7±0.3 <0.01 0.3±0.0 0.3±0.0 0.53

7 5.3±0.4 6.0±0.4 0.22 6.1±0.2 7.2±0.2 <0.01 11.4±0.4 13.2±0.4 <0.01 0.9±0.0 0.8±0.0 0.38

8 0.6±0.2 0.4±0.2 0.39 7.1±0.2 8.6±0.2 <0.01 7.8±0.2 9.0±0.2 <0.01 0∗ 0∗ 0.27

9 0 0 na 7.4±0.2 8.8±0.2 <0.01 7.3±0.2 8.8±0.2 <0.01 0 0 na

10 1.6±0.3 1.0±0.3 0.20 6.5±0.2 7.7±0.1 <0.01 7.5±0.4 8.8±0.3 <0.01 0.1±0.0 0.1±0.0 0.06

11 4.0±0.4 4.4±0.3 0.44 5.7±0.1 6.8±0.1 <0.01 9.8±0.4 11.2±0.3 <0.01 0.7±0.1 0.7±0.0 0.79

12 4.4±0.4 4.5±0.3 0.81 5.6±0.2 6.9±0.1 <0.01 9.9±0.4 11.4±0.3 <0.01 0.8±0.1 0.7±0.1 0.13

13 5.5±0.3 5.9±0.3 0.42 6.0±0.2 6.5±0.2 <0.05 11.0±0.4 12.4±0.4 <0.05 0.9±0.1 0.9±0.2 0.98

14 0.7±0.3 0.7±0.2 0.98 6.6±0.2 7.9±0.2 <0.01 7.3±0.3 8.7±0.3 <0.01 0.1±0.0 0.1±0.0 0.61

15 2.3±0.3 2.1±0.3 0.76 5.7±0.2 6.6±0.2 <0.01 8.0±0.3 8.7±0.2 <0.05 0.4±0.1 0.3±0.1 0.29

16 6.7±0.3 7.6±0.3 0.05 5.9±0.2 6.4±0.2 <0.05 12.5±0.4 14.0±0.4 <0.05 1.1±0.1 1.2±0.1 0.54

Table 4 - ES thicknesses of trabeculated, compacted and total layer and trabeculated/compacted ratio in female and male subjects

Segment Trabeculated p Compacted p Total layer p Trab/C ratio p

F M F M F M F M

1 0.6±0.2 0.9±0.2 0.22 12.6±0.4 14.9±0.4 <0.01 13.1±0.4 15.9±0.4 <0.01 0 0.1±0.0 0.45

2 0 0 na 13.0±0.4 15.1±0.3 <0.01 13.0±0.4 15.1±0.3 <0.01 0 0 na

3 0 0 na 10.7±0.3 12.7±0.3 <0.01 10.7±0.3 12.7±0.3 <0.01 0 0 na

4 0.1±0.0 0.3±0.1 0.13 12.2±0.3 14.0±0.3 <0.01 12.2±0.3 14.4±0.3 <0.01 0∗ 0∗ 0.32

5 0.6±0.1 0.6±0.1 0.97 12.1±0.3 14.0±0.3 <0.01 12.7±0.3 14.5±0.3 <0.01 0.1±0.0 0.1±0.0 0.66

6 0.5±0.1 0.6±0.2 0.47 11.9±0.3 13.5±0.3 <0.01 12.3±0.3 14.2±0.3 <0.01 0.1±0.0 0.1±0.0 0.67

7 5.3±0.4 6.0±0.3 0.22 10.2±0.4 12.5±0.3 <0.01 14.6±0.4 17.1±0.4 <0.01 0.5±0.1 0.4±0.0 0.07

8 0.6±0.2 0.3±0.2 0.28 11.8±0.4 14.0±0.3 <0.01 12.4±0.4 14.3±0.3 <0.01 0∗ 0∗ 0.68

9 0 0 na 11.8±0.3 14.0±0.3 <0.01 11.8±0.3 14.0±0.3 <0.01 0 0 na

10 1.2±0.3 0.7±0.2 0.14 11.8±0.4 13.5±0.3 <0.01 12.4±0.4 14.1±0.3 <0.01 0.1±0.0 0.1±0.0 0.09

11 2.8±0.3 3.4±0.4 0.23 10.8±0.4 12.6±0.4 <0.01 13.5±0.4 16.0±0.4 <0.01 0.3±0.0 0.3±0.0 0.84

12 2.4±0.3 3.2±0.3 0.10 10.5±0.4 12.1±0.3 <0.01 13.0±0.4 15.3±0.3 <0.01 0.2±0.0 0.3±0.0 0.52

13 4.1±0.3 4.2±0.3 0.91 11.1±0.3 12.1±0.3 <0.01 15.2±0.3 16.4±0.4 <0.01 0.4±0.0 0.3±0.0 0.30

14 0.5±0.2 0.4±0.2 0.67 12.0±0.3 13.5±0.3 <0.01 12.5±0.3 14.0±0.3 <0.01 0∗ 0∗ 0.45

15 1.5±0.3 1.5±0.3 0.93 10.6±0.4 12.2±0.4 <0.01 12.1±0.4 13.7±0.4 <0.01 0.2±0.0 0.2±0.0 0.47

16 4.8±0.2 5.3±0.4 0.24 10.2±0.3 12.3±0.3 <0.01 15.0±0.3 17.6±0.5 <0.01 0.5±0.0 0.5±0.0 0.29

Table 5 - Trabecular, compacted and total layer thickening in female and male subjects.

Segment Trabecular

thickening

p Compacted

thickening

p Total layer

thickening

p

F M F M F M

1 -30±7 -30±7 0.68 73±4 71±4 0.83 45±5 42±4 ns

2 0 0 na 51±3 46±3 0.20 48±4 44±4 ns

3 0 0 na 36±2 33±2 0.73 30±4 33±3 ns

4 -34±5 -51±6 0.79 96±2 66±3 0.28 67±6 59±5 ns

5 -30±6 -32±7 0.48 88±5 80±5 0.54 63±6 59±5 ns

6 -20±7 -21±7 0.54 84±5 72±4 0.08 59±6 54±5 ns

7 -21±6 -20±5 0.17 75±5 76±4 0.80 33±3 35±4 ns

8 -7±2 -4±1 0.56 67±4 63±3 0.40 62±4 60±3 ns

9 0 0 na 59±4 60±3 0.84 59±4 57±4 ns

10 -14±6 -10±7 0.03 74±4 74±4 0.96 60±4 63±5 ns

11 -29±7 -24±7 0.62 88±5 86±5 0.76 80±9 87±7 ns

12 -42±7 -29±6 0.18 91±6 75±4 0.03 36±5 36±5 ns

13 -19±5 -14±6 0.70 83±5 90±5 0.31 36±4 37±5 ns

14 -31±8 -33±9 0.58 84±5 69±5 0.03 78±6 60±6 ns

15 -31±8 -34±7 0.83 86±6 84±4 0.77 61±6 65±6 ns

16 -20±5 -29±5 0.19 76±6 94±5 0.06 26±4 27±4 ns

Movie 1 Legend: Typical selection of the basal, mid-cavity and apical movies which was

used in selected cases to help locate the boundary between the compact and trabeculated

myocardium at end-systole.