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Published on: August 2, 2024
Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound
Yasbanoo Moayedi1,2, Chun Po S Fan2, Maxime Tremblay-Gravel1
1Section of Heart Failure, Cardiac Transplant, and Mechanical Circulatory Support, Department of Medicine, Stanford University, Stanford, CA, USA.
Insights
Donor-derived atherosclerosis increases cardiac allograft vasculopathy (CAV) risk. Early prednisone discontinuation and proliferation signal inhibitor (PSI) use reduce CAV incidence, aiding tailored patient management after heart transplantation.
Area of Science:
- Cardiology
- Transplantation Immunology
- Vascular Biology
Background:
- Cardiac allograft vasculopathy (CAV) is a primary cause of late graft loss after heart transplantation.
- Limited data exists on the impact of donor-derived atherosclerosis (DA), early prednisone discontinuation, and early proliferation signal inhibitor (PSI) use on CAV development.
- Intravascular ultrasound (IVUS) is a key imaging modality for assessing CAV.
Purpose of the Study:
- To investigate the association between donor-derived atherosclerosis (DA) and the development of CAV.
- To evaluate the impact of early prednisone discontinuation and PSI initiation on CAV incidence.
- To identify clinical risk factors for CAV using serial IVUS data.
Main Methods:
- Retrospective study of adult heart transplant recipients (2008-2017) with serial IVUS over 5 years.
- DA defined by baseline maximal intimal thickness (MIT) ≥0.5 mm; CAV defined by MIT ≥1 mm or significant increase.
- Multivariable regression and multistate models used to assess risk factors and treatment associations.
Main Results:
- Donor-derived atherosclerosis (DA) was present in 40% of patients and significantly associated with higher CAV incidence (59% vs. 41%).
- Significant CAV risk factors included male sex, non-Caucasian race, low BMI, longer ischemic time, older donor age, and rejection with hemodynamic compromise.
- Early prednisone discontinuation (within 1 year) and early PSI initiation (within 2 years) were associated with a reduced risk of CAV.
Conclusions:
- Donor-derived atherosclerosis is a significant predictor of CAV development in heart transplant recipients.
- Early cessation of prednisone and initiation of PSI therapy can mitigate CAV risk.
- Utilizing early IVUS findings can guide personalized patient management strategies to improve long-term graft survival.
Background:
Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS).
Methods:
Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV.
Results:
Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non-Caucasian race (HR = 1.98, p = .011), BMI < 18 kg/m2 (HR = 4.596, p = .042), longer ischemic time (HR = 1.374, p = .028), older donor age (HR = 1.158, p = .009), and rejection with hemodynamic compromise within the first year (HR = 2.858, p = .043). Prednisone discontinuation within 1 year was associated with a lower risk of CAV (HR 0.58 p = .047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p < .001).
Conclusion:
In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.
