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Co-localization of Disturbed Flow Patterns and Occlusive Cardiac Allograft Vasculopathy Lesion Formation in Heart Transplant Patients

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Abstract

Cardiac allograft vasculopathy (CAV) is one of the leading causes of morbidity and morality in orthotopic heart transplant (HTx) patients. While disturbed flow patterns have been linked to the spatial localization of atherosclerosis, the role of hemodynamics in CAV development has not been examined. HTx patients (n = 5) requiring percutaneous coronary intervention (PCI) for a focal, epicardial lesion were studied. Angiographic images were retrospectively obtained from baseline (i.e., in the presence of no observed disease) and follow-up catheterizations (i.e., at the time of PCI; 12.4 ± 2.6 years post-HTx). Patient-specific computational models were created from baseline images. Computational fluid dynamic techniques were employed to quantify the hemodynamic environment, which was expressed as normalized time-averaged WSS (TAWSSnorm; measure of temporal WSS magnitude) and normalized WSS angle deviation (WSSADnorm; measure of instantaneous WSS vector oscillation) values. Baseline hemodynamic and follow-up angiographic data were co-registered to investigate the association between WSS and subsequent occlusive CAV lesion location. Results indicate a high degree of co-localization between baseline low WSS data and follow-up occlusive CAV lesion. Local minima in TAWSSnorm were located 2.5 ± 0.6 mm from the site of PCI. Furthermore, local maxima in WSSADnorm were located 3.9 ± 0.7 mm from the site of PCI. In 3 patients, the occlusive lesion formed in a region that was subjected to both low and oscillatory WSS at baseline. There was discernable spatial co-localization between baseline disturbed flow patterns and follow-up CAV lesions requiring PCI. These results suggest a role of fluid mechanics in the development of focal, flow-limiting CAV lesions.

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Acknowledgments

Funding for this research was provided by American Heart Association (AHA) Postdoctoral Fellowships (to L. H. T. and D. S. M.) and the Georgia Research Alliance (to D. P. G.).

Human Studies/Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation as mandated by the Institutional Review Board at Emory University. Due to the retrospective nature of this investigation, informed consent was not required for the patients examined, and all data utilized was acquired for clinical reasons (i.e., these data were not investigational).

Animal studies

No animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 1760 Haygood Drive, Suite W 200, 30322-4600, Atlanta, GA, USA

    Lucas H. Timmins, David S. Molony, John N. Oshinski & Don P. Giddens

  2. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Lucas H. Timmins, Divya Gupta, Michel T. Corban & Habib Samady

  3. Department of Radiology and Imaging Sciences, Emory University School of Medicine, 30322, Atlanta, GA, USA

    John N. Oshinski

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  1. Lucas H. Timmins
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Correspondence to Lucas H. Timmins.

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Associate Editor Ajit P. Yoganathan oversaw the review of this article.

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Angiographic reconstruction data were exported from the reconstruction software (IC-PRO, Paieon, Inc., Rosh Ha’ayin, Israel) as 3D Cartesian coordinates of the centerline and a corresponding diameter at each centerline point. Data were reported at increments of 0.25 mm along the vessel centerline, which is the approximate resolution of the angiographic images (ranged from 0.21 – 0.25 mm/pixel for patient cohort). As a result of the resolution of the imaging modality, and since the reconstructed artery boundary must be defined as an entire pixel (Supplemental Fig. 1A insert), small changes in artery diameter occurred in local regions. As a result, small oscillations in diameter data were observed along the length of the artery (Supplemental Fig. 1B, black curve). For example, in Supplemental Fig. IB between the centerline axial position of 33 – 37 mm, there is a noticeable oscillation with an amplitude of ~0.25 mm in the diameter. This amplitude value corresponds precisely to the resolution of the imaging data and is likely a limitation of the reconstruction technique. These oscillations are non-physiologic and strongly affect the resulting hemodynamic data as WSS is inversely related to the cube of the artery radius. For example, the artificial oscillations results in a banded appearance of the TAWSSnorm distributions (Supplemental Fig. 1D) as well as the analysis of the hemodynamics parameters along the major vessel of interest (Supplemental Fig. 1E).

To alleviate any non-anatomical artifacts on the reconstructed geometries, a smoothing algorithm was applied to the reconstruction data prior to computational model construction and CFD. Reconstructed centerline data were undersampled (i.e., smoothed) by extracting data points every 1.25 mm along the artery axes (main vessel and branches) and applying a weighted linear least squares regression smoothing algorithm. As a result, the previously observed oscillations were removed, while still preserving the anatomical shape of the artery (Supplemental Fig. 1B, C). Furthermore, the banded appearance of the resulting non-smoothed TAWSSnorm distributions was removed, yet the global hemodynamic environment was not significantly altered (Supplemental Fig. 1D, E). The smoothing algorithm still allowed for the accurate co-localization of disturbed baseline disturbed flow patterns and follow-up CAV lesion formation, and likely more accurately represented the anatomic physical system.

Supplement Fig. 1 Caption

Undersampling (smoothing) Algorithm of Angiographic Reconstructions. (A) Single-plane angiographic images with magnified insert to highlight the oscillations (ripples) in the diameter. (B) Average diameter along vessel main axis for unsmoothed and smoothed data. Note the oscillations in the unsmoothed diameter over small axial lengths. Vertical dotted lines denote location of side branches. (C) Reconstructed 3D geometries. (D) TAWSSnorm distributions. (E) TAWSSnorm values along main axis of vessel.

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Timmins, L.H., Gupta, D., Corban, M.T. et al. Co-localization of Disturbed Flow Patterns and Occlusive Cardiac Allograft Vasculopathy Lesion Formation in Heart Transplant Patients. Cardiovasc Eng Tech 6, 25–35 (2015). https://doi.org/10.1007/s13239-014-0198-2

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