J Korean Soc Transplant.  2017 Mar;31(1):25-33. 10.4285/jkstn.2017.31.1.25.

Non-invasive Myocardial Strain Imaging to Evaluate Graft Failure in Cardiac Xenotransplantation

Affiliations
  • 1Department of Cardiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
  • 2Department of Thoracic and Cardiovascular Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
  • 3Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
  • 4Department of Nephrology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
  • 5Department of Ophthalmology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
  • 6Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea. ijyun@kuh.ac.kr
  • 7Haeen Biomedical Research Institute, Genia Inc., Seongnam, Korea.
  • 8Animal Biotechnology Division, National Institute of Animal Science, Suwon, Korea.
  • 9Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
The shortage of human hearts for allotransplantation makes xenotransplantation a possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; however, this occasionally results in poor incision wound healing or infection. To date, no method of noninvasive imaging for early detection of xenograft rejection has been established. We hypothesized that ultrasound speckle tracking would better detect xenograft failure than routine left ventricular ejection fractions (EF).
METHODS
From August 2013 to July 2015, a total of six cardiac heterotopic xenotransplants (α 1, 3-galactosyltransferase gene-knockout porcine heart) into cynomolgus monkeys were monitored with echocardiography every 3 to 7 days. M-mode and two-dimensional (2D)-EF measurements and myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy, as well as the necropsy.
RESULTS
Myocardial speckle tracking analysis was feasible in all six cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection occurred. Cardiac xenograft failure appeared as two types: a dilated pattern with decreased EF or a myocardial-thickening pattern with preserved EF. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains, but normal-range EF. Xenograft functional decline was significant with respect to radial or circumferential strain (P=0.028), but not to conventional M-mode or 2D-EFs (P=0.600, P=0.340, respectively).
CONCLUSIONS
Radial and circumferential strains were significantly decreased in both types of xenograft failure, regardless of EF. Further studies are warranted to correlate the strain analysis and immunopathological details.

Keyword

Heterologous transplantation; Heart transplantation; Echocardiography; Histopathology
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