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Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Peripheral microvascular dysfunction is associated with plaque progression and adverse long-term outcomes in heart
Ilke Ozcan1, Takumi Toya1,2, Michel T Corban1
1Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA.
Insights
Peripheral endothelial dysfunction (PED) in heart transplant recipients predicts worse outcomes. This condition is linked to faster plaque progression and a higher risk of major adverse cardiovascular events (MACE) post-transplant.
Area of Science:
- Cardiology
- Transplantation Immunology
- Vascular Biology
Background:
- Cardiac allograft vasculopathy (CAV) significantly increases morbidity and mortality after heart transplantation.
- Peripheral endothelial dysfunction (PED) is a known risk factor for atherosclerosis and major adverse cardiovascular events (MACE) in the general population.
Purpose of the Study:
- To investigate the association between PED and CAV progression after heart transplantation.
- To determine if PED predicts future MACE in heart transplant recipients.
Main Methods:
- Sixty-six heart transplant patients underwent serial intravascular ultrasound (IVUS) for CAV surveillance and baseline peripheral endothelial function assessment.
- PED was defined as a reactive hyperemia peripheral arterial tonometry index < 2.
- CAV progression was quantified by changes in plaque volume and plaque index over a median follow-up of 3.0 years.
Main Results:
- Patients with PED exhibited significantly greater yearly plaque progression (0.50 vs. 0.15 mm³/mm/year, P=0.02) and a higher plaque index change (2.41% vs. 0.69%, P=0.01).
- PED was independently associated with an increased risk of MACE (HR 2.15, P=0.03) during a median follow-up of 8.2 years.
- MACE included revascularization, heart failure hospitalization, stroke, myocardial infarction, re-transplantation, and death.
Conclusions:
- Peripheral endothelial dysfunction is a significant predictor of accelerated plaque progression in cardiac allografts.
- PED assessment may serve as a valuable tool for stratifying cardiovascular risk in heart transplant recipients.
- These findings highlight the importance of monitoring endothelial function for long-term outcomes in transplanted hearts.
Aims:
Cardiac allograft vasculopathy (CAV) is the major cause of increased morbidity and mortality after heart transplantation. Peripheral endothelial dysfunction (PED) is associated with early atherosclerosis and future risk of major adverse cardiovascular events (MACE) in non-heart transplant population. We aimed to investigate the association of PED with future MACE, and plaque progression assessed by intravascular ultrasound (IVUS) after heart transplantation.
Methods And Results:
We included 66 transplant patients who underwent serial IVUS surveillance for CAV and baseline assessment of peripheral endothelial function using reactive hyperaemia peripheral arterial tonometry. PED was defined as reactive hyperaemia index < 2. The primary endpoint of the study was to investigate the association of PED with CAV progression assessed by intravascular ultrasound (IVUS). CAV progression was assessed as the change (Δ) in plaque volume divided by segment length, and Δ plaque index (plaque volume/vessel volume), adjusted for the time between IVUS measurements (median 3.0 [2.2, 3.1] years). The secondary endpoint was to investigate the association between PED and future MACE, which was defined as any incident of revascularization, heart failure hospitalization, stroke, myocardial infarction, re-transplantation, and death. Patients with PED (n = 27) had more yearly plaque progression (0.50 ± 0.66 vs. 0.15 ± 0.50 mm3 /mm/year, P = 0.02) and a higher Δ plaque index (2.41 ± 2.53% vs. 0.69 ± 2.22%, P = 0.01). Patients with PED were more likely to experience MACE during a median follow-up of 8.2 years (interquartile range [7.6, 8.4]), after adjustment for potential cofounders such as age, high-density lipoprotein cholesterol levels, total rejection score, baseline International Society for Heart & Lung Transplantation CAV grade, and indication of transplantation. (hazard ratio 2.15, 95% confidence interval [1.09, 4.23], P = 0.03).
Conclusions:
Peripheral endothelial dysfunction is associated with increased plaque progression and adverse long-term cardiovascular outcomes in transplant patients. PED assessment might be a useful clinical tool for risk stratification after heart transplantation.
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