Alexander Gotschy1,2,3, Rabea Schlenker1,2, Sebastian Kozerke1, Robert Manka2,3, and Christian T Stoeck1,4
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, 2Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland, 3Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland, 4Center for Preclinical Development, University of Zurich and University Hospital Zurich, Zurich, Switzerland
Synopsis
Keywords: Myocardium, Cardiomyopathy, non-compaction , cardiac diffusion tensor imaging, cDTI
Motivation: Left ventricular non-compaction cardiomyopathy (LVNC) is characterized by the presence of excessive trabeculation in the left ventricle.
Goal(s): To characterize the myocardial microstructure of LVNC patients in comparison to healthy controls using cardiac Diffusion Tensor Imaging (cDTI).
Approach: Second order motion compensated spin echo cardiac DTI was acquired in six LVNC patients and six healthy controls. Myocyte aggregate orientation is characterized by helix angle and relative percentage of right handed helical orientated myocytes.
Results: In the compacted myocardium, LVNC patients exhibited lower endocardial helix angles and a loss of the endocardial right handed helix when compared to controls.
Impact: Our findings indicate that in LVNC patients, a
portion of the endocardial helix is dissolved into the non-compacted
myocardium, which may impair optimal myocardial contraction in the affected
segments as well as apical rotation as observed in LVNC
patients.
Introduction
Left ventricular non-compaction cardiomyopathy
(LVNC) is a rare heart condition characterized by the presence of excessive
trabeculation in the left ventricle (LV). While early investigations of the disease
reported a high mortality and morbidity from heart failure, thrombo-embolic
events and ventricular arrhythmias, current evidence shows that the finding of excessive
tabeculation is not associated with impaired prognosis in otherwise healthy
subjects and does not alter prognosis in patients with dilated or hypertrophic
cardiomyopathy. Therefore, the status of LVNC as a distinct cardiomyopathy is
currently debated [1]. However, the characteristic
morphology of LVNC and consistent findings of reduced strain and apical
rotation imply pathological myocardial alterations [2]. Cardiac diffusion tensor imaging (cDTI)
enables the assessment of cardiac microstructure and myocyte aggregate orientation
[3]. The objective of the present work
was to investigate the myocardial microstructure of LVNC patients in comparison
to healthy controls using cDTI.Methods
In
this preliminary study we included six patients diagnosed with LVNC as well as six healthy controls. All study participants provided
written informed consent and the protocol was approved by the local ethics
committee. CMR was performed on a clinical 1.5T system (Achieva, Philips
Healthcare, Best, The Netherlands) with a high-performance gradient system (80mT/m
maximum gradient strength, 100mT/m/ms slew rate) and included functional cine
imaging as well as cDTI. Imaging
parameters are provided in Table 1. In brief: functional
imaging was performed by retrospectively ECG gated, balance
SSFP cine imaging in short axis orientation covering the entire heart; cDTI was
performed using a second order motion compensated spine echo sequence [3] with water selective
spectral spatial excitation, a reduced FOV [4], respiratory
navigator based slice tracking and ECG triggering to 65% end systole. Cine data
was evaluated using clinical evaluation software (ISP, Philips Healthcare,
Best, The Netherlands) and
LV volumes and function are reported.
cDTI data was first registered [5] and consequently
complex averaged [6]. Diffusion Tensors
were computed using an in-house software tool (Matlab, Mathworks, Natick, MA,
USA) and
MD, FA, Helix angle (HA) maps as well as the relative percentage of right-handed helical alignment (HA>30°) of
myocyte aggregates are reported.
One ex-vivo
heart was imaged post explanation from an additional heart transplant patient.
The sample was formalin fixated (4% buffered formalin solution) and imaged using
a spin echo sequence with 3D segmented echo planar imaging readout and
conventional Stejskal-Tanner diffusion encoding. Imaging was performed on the
same scanner as in-vivo imaging. Fibre tracking was performed using DSI studio.Results
In vivo:
Table 2 shows the baseline characteristics
of the LVNC patient and control groups. LVNC patients had larger LVs, a higher non-compacted
to compacted tissue (NC:C) ratio and a trend towards lower LVEF. Two LVNC
patients had reduced LVEF (<50%). In the compacted myocardium, LVNC patients
exhibited lower endocardial helix angles (p<0.01) and a loss of the
endocardial right handed helix (p=0.04) when compared to controls. The absolute
E2A sheet angle was lower in LVNC patients (p=0.05) while MD, FA and the HA
slope where not statistically significant different between both groups (Figure 1). Figure 2 a) and b) shows representative HA maps of an
LVNC patient and a control subject. When viewed on a segmental level, the loss
of the endocardial right-handed helix was most prominent in the lateral and
inferior segments, which are known to be most affected by LVNC (Figure 2 c).
Ex vivo:
Figure 3 shows the fiber tracking results of
the post-transplant ex-vivo heart as well as the degree of non-compaction in
the pathology image. The entire lateral wall presents endocardial non-compacted
myocardium. Fiber tracking at epi, meso and endocardium of the compacted
myocardium in the remote (septal), borderline (anterior) and affected (lateral)
area reveals the lack of right handed endocardial (green) helical structure in
the affected region.Conclusion
Our
findings indicate that in LVNC patients, a portion of the endocardial helix is
dissolved into the non-compacted myocardium, which may impair optimal
myocardial contraction in the affected segments. In conjunction with the ex
vivo findings, we hypothesise that the thinned,
compacted myocardium in the lateral and inferior segments of LVNC patients
contains only the midmyocardial and epicardial helical structures of a normal
myocardium. This observation could explain the lack of apical rotation observed
in LVNC patients. The finding of reduced absolute E2A has previously been described
in patients with dilated cardiomyopathy (DCM), which appears coherent given the
known overlap between DCM and LVNC cohorts. The small number of patients is the
major limitation of this ongoing study. Acknowledgements
No acknowledgement found.References
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