Author + information
- Published online September 3, 2018.
- Zohya Khalique, MBBS,
- Pedro F. Ferreira, PhD,
- Andrew D. Scott, PhD,
- Sonia Nielles-Vallespin, PhD,
- Philip J. Kilner, MD,
- Robert Kutys, MS,
- Maria Romero, MD,
- Andrew E. Arai, MD,
- David N. Firmin, PhD and
- Dudley J. Pennell, FMedSci∗ ()
- ↵∗Royal Brompton Hospital, Sydney Street, London, SW3 6NP, United Kingdom
To the Editor:
In situs inversus totalis (SIT), there is mirror imaging of the situs solitus (SS) visceral arrangement; however, there are no histological studies examining the myocardial microstructure. Diffusion tensor cardiac magnetic resonance (DT-CMR) noninvasively interrogates the myocardial microstructure via the parameters helix angle (HA) and absolute angle of the second eigenvector (E2A). Here, HA provides mean intra-voxel myocyte orientation, and absolute E2A is a DT-CMR measure of sheetlet orientation (1). For the first time, we use DT-CMR to identify the microstructure of the human SIT heart in vivo and relate this information to measures of left ventricular (LV) function.
The in vivo cardiac diffusion–weighted stimulated echo acquisition mode single-shot echo planar imaging sequence and analysis have been described previously (1). DT-CMR was performed in basal, mid, and apical short-axis slices. An ex vivo heart was scanned by using a higher resolution DT-CMR protocol. Post-processing used MATLAB (MathWorks, Natick, Massachusetts) and ParaView (KitWare, Santa Fe, New Mexico) software. Strain and torsion were obtained from cine displacement encoding with stimulated echoes data. Torsion was negative when apical rotation was more anticlockwise than basal, as viewed from the apex.
Twelve patients with SIT and 12 SS control subjects (age: 39.5 years [interquartile range (IQR): 29 years] vs. 34.5 years [IQR: 31 years]; p = 0.5; 3 male subjects in each group) underwent DT-CMR. One SS patient and 1 SIT patient underwent whole heart DT-CMR. The SIT and SS hearts had similar size, mass, and biventricular ejection fraction (p > 0.05). There were marked differences between SIT and SS HA patterns. All SS hearts demonstrated the expected smooth transition from negative left-handed HA epicardially, through circumferential in the mesocardium, to positive right-handed HA in the endocardium. However, in SIT patients and ex vivo hearts, the pattern was an inverted HA arrangement basally, with positive HAs in the epicardium and negative HAs in the endocardium. There was a mid-ventricular transition zone, and trend toward an overall more normal apical HA pattern (Figure 1A).
Median (interquartile range) global diastolic E2A was similar between groups: SS 18° (IQR: 9°); SIT 18° (IQR: 10°); p = 0.67. These findings indicate expected wall-parallel sheetlet orientation (Figure 1B). In SS, the systolic E2A rose to 62° (IQR: 8°) (more wall-perpendicular sheetlet alignment). However, in SIT, the systolic E2A was reduced (46° [IQR: 10°]; p < 0.001), indicating impaired sheetlet mobility through the cardiac cycle (SS 44° [IQR: 10°] vs. SIT 27° [IQR: 12°]; p < 0.001).
Peak radial and circumferential strain did not differ between SIT and SS at base or apically. However, in the mid-ventricular transition zone, both peak radial and circumferential strain (mean ± SD) were reduced in SIT (SS 0.56 ± 0.16 vs. SIT 0.40 ± 0.16 [p = 0.02] and SS –0.18 ± 0.01 vs. SIT –0.16 ± 0.02 [p = 0.04], respectively). Torsion was negative in all SS subjects. In SIT, torsion patterns were heterogeneous, ranging between similar and opposite to the SS pattern. There was significantly lower mean ± SD absolute torsion in SIT: 4.1 ± 2.4° vs. 7.7 ± 2.5° (p = 0.002).
To our knowledge, this study is the first in vivo DT-CMR trial of SIT in humans and the first demonstration of departure from the typical mammalian helical ordering of myocytes, with corresponding ex vivo human results confirming the in vivo findings. Limitations of the study include strain sensitivity, limited spatial resolution, and our relatively small heterogeneous cohort (1).
Myocardial microstructure is central to the dynamics of LV function. The helical arrangement of myocytes determines myocardial rotation and torsion (2,3). In SS, there is a net clockwise rotation basally and anticlockwise rotation apically. Rotation needs to be sufficiently opposite at base and apex to maintain torsion. The deranged myocyte arrangement in SIT affects the generation of normal LV torsion. It may also potentially impair the ability of the left ventricle to increase torsion as an adaptive mechanism, as in aortic stenosis (4). In SIT, there was also impaired sheetlet mobility, which may result from myocyte derangement affecting the transverse shears and associated sheetlet reorientation (3).
The clinical relevance of the altered myocardial microstructure in SIT and its effects on LV function and reserve require further study. Limited data suggest normal life expectancy in SIT, but this outcome assumes normal heart structure. We have now shown that the SIT heart is not a simple mirror-image and that significant microstructural differences are present. With no longitudinal studies of cardiac function in patients with SIT, the long-term effect, if any, of these microstructural derangements requires additional study.
Please note: This work was supported by the National Institute for Health Research Funded Cardiovascular Biomedical Research Unit at The Royal Brompton Hospital and Imperial College London and the National Heart, Lung, and Blood Institute, National Institutes of Health by the Division of Intramural Research, and Department of Health and Human Services (HL004607-18). Prof. Pennell receives research support from Siemens; and is a stockholder and director of Cardiovascular Imaging Solutions. Prof. Firmin receives research support from Siemens. Dr. Arai is a principal investigator on a U.S. government Cooperative Research and Development Agreement with Siemens Medical Solutions (HL-CR-05-004). Profs. Firmin and Pennell contributed equally to this work and are joint senior authors.
- 2018 American College of Cardiology Foundation
- Nielles-Vallespin S.,
- Khalique Z.,
- Ferreira P.F.,
- et al.
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