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Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant
S F Davis1, A C Yeung, I T Meredith
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, USA.
Insights
Early endothelial dysfunction after heart transplant predicts transplant coronary arteriosclerosis. This finding using intravascular ultrasound may identify patients for therapeutic trials.
Area of Science:
- Cardiovascular Medicine
- Transplantation Immunology
- Vascular Biology
Background:
- Accelerated coronary arteriosclerosis significantly impacts long-term survival post-cardiac transplantation.
- Endothelial dysfunction is a frequent early complication following transplantation.
- The serial relationship between early endothelial dysfunction and allograft arteriosclerosis development remains under-investigated.
Purpose of the Study:
- To investigate if an early endothelial constrictor response to acetylcholine predicts transplant coronary arteriosclerosis.
- To serially analyze the association between early endothelial dysfunction and the development of allograft arteriosclerosis using intravascular ultrasound.
Main Methods:
- Assessed endothelium-dependent vasomotion in 20 heart transplant recipients via serial intracoronary acetylcholine infusion.
- Measured percent change in coronary artery diameter using quantitative angiography.
- Evaluated arteriosclerosis development using intravascular ultrasound, quantifying intimal index (Ii) and maximal intimal thickness (Mt) changes over 1 year.
Main Results:
- Coronary segments exhibiting endothelial dysfunction (constriction ≥ 5%) showed significantly greater increases in intimal index and thickness by 1 year post-transplant.
- Segments with endothelial dysfunction had a mean delta Ii of 7±2% and delta Mt of 140±40 microns, compared to 2±1% and 50±20 microns for normal segments (P<.05).
- No other examined parameters predicted allograft arteriosclerosis development within the first year.
Conclusions:
- Early endothelial dysfunction, identified by acetylcholine response, predicts the development of allograft arteriosclerosis in the first year post-cardiac transplantation.
- This early pathophysiological marker holds potential utility in guiding therapeutic interventions and clinical trials.
Background:
Accelerated coronary arteriosclerosis is the major obstacle to long-term survival after cardiac transplantation. Endothelial dysfunction is common early posttransplant. The relationship between early endothelial dysfunction and the development of allograft arteriosclerosis has not been analyzed serially with intravascular ultrasound in the same patients. We hypothesized that an early constrictor response to acetylcholine, indicative of endothelial dysfunction, may predict the development of transplant coronary arteriosclerosis.
Methods And Results:
Endothelium-dependent vasomotion was assessed early posttransplant in 20 patients by serial intracoronary acetylcholine infusion, and the percent change in diameter was measured by quantitative angiography. The development of arteriosclerosis was studied by use of intravascular ultrasound in the same 20 patients by quantifying the changes in intimal index (delta Ii) and maximal intimal thickness [delta Mt] of 46 matched coronary segments between initial and 1-year follow-up studies. Coronary segments with endothelial dysfunction (constriction > or = 5%; n = 23) demonstrated a significantly greater increase in mean Ii and Mt by 1 year posttransplant compared with segments with normal endothelial function (n = 23) (delta Ii = 7 +/- 2% versus 2 +/- 1% [P < .05] and delta Mt = 140 +/- 40 versus 50 +/- 20 microns [P < .05]). No other parameters examined predicted the development of allograft arteriosclerosis in the initial year posttransplant.
Conclusions:
Paired studies that used intravascular ultrasound showed that early endothelial dysfunction predicts the development of allograft arteriosclerosis during the initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic trials.