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Updated: Jul 14, 2026

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation
Published on: April 27, 2019
Changes in coronary anatomy and physiology after heart transplantation
Atsushi Hirohata1, Mamoo Nakamura, Katsuhisa Waseda
1Center for Research in Cardiovascular Interventions, Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California, USA.
Insights
Cardiac allograft vasculopathy (CAV) shows early epicardial changes after heart transplantation (HT). Microvascular dysfunction appears later, influencing coronary artery physiology and anatomy over time.
Area of Science:
- Cardiology
- Transplantation Medicine
- Vascular Biology
Background:
- Cardiac allograft vasculopathy (CAV) affects both epicardial and microvascular coronary systems after heart transplantation (HT).
- The precise timing of abnormalities in these compartments and their physiological-anatomical correlation remain unclear.
Purpose of the Study:
- To define the temporal development of CAV abnormalities in epicardial and microvascular coronary systems.
- To correlate anatomical changes with physiological dysfunction in asymptomatic heart transplant recipients.
Main Methods:
- Invasive evaluation using intravascular ultrasound, fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance (IMR).
- Assessment performed in the left anterior descending coronary artery of 151 asymptomatic heart transplant recipients (0 to >5 years post-HT).
Main Results:
- Early after HT (within 1 year), significant decreases in fractional flow reserve and increases in plaque volume were observed.
- An inverse correlation between epicardial physiology and anatomy was found (r = -0.58, p <0.0001).
- Microvascular resistance (IMR) was lower early post-HT, suggesting later microvascular involvement, and paradoxically, increased fractional flow reserve with higher IMR.
Conclusions:
- Early anatomical and physiological evidence of epicardial CAV is present after heart transplantation.
- Later in the post-transplant course, microvascular dysfunction may influence or mask the physiological impact of epicardial CAV.
Abstract:
Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.
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