Noninvasive detection of early coronary allograft vasculopathy using myocardial contrast echocardiography
O Nguyen, H Slone, G Derk, B Karki, B Davidson, J Hodovan, J SteinerAbstract
Background
Coronary allograft vasculopathy (CAV) is a leading cause of late graft dysfunction after heart transplantation, affecting up to 50% of recipients by 10 years. Despite its diffuse pathobiology involving both epicardial and microvascular vessels, invasive coronary angiography (ICA) remains the diagnostic standard. ICA not only exposes patients to nephrotoxic contrast and ionizing radiation but lacks the ability to evaluate the physiologic significance of the vasculopathy on myocardial blood flow. Myocardial contrast echocardiography (MCE) provides radiation-free assessment of myocardial perfusion and ventricular function. We compared the diagnostic performance of MCE with ICA for CAV detection.
Methods
We conducted a single-center retrospective study of adult heart transplant recipients who underwent both MCE and ICA between 2019-2025. Patients with paired studies within 24 months were included (n=53; 118 pairs). ICA findings were graded using ISHLT criteria. Burst replenishment MCE perfusion was performed at rest and during regadenoson-induced hyperemia. MCE image sequences were interpreted by specially-trained cardiologists. Abnormal perfusion by MCE was defined as lack of complete myocardial replenishment within 5 beats (rest) or 1-2 beats (hyperemic stress) following a destructive pulse. In a secondary analysis, CAV status (CAV+/–) was adjudicated by integrated review of symptoms, longitudinal angiography, echocardiography, and clinical data. Sensitivity, specificity, AUC, and inter-modality concordance were evaluated overall and by ISHLT grade.
Results
MCE detected perfusion abnormalities in 40.9% of patients with ISHLT CAV0, 45.7% with CAV1, and 83.3% with CAV≥2. Mean (SD) interval between paired studies was 59.6 (30.8) weeks. Secondary analysis highlighted the discordance between modalities, which was most common in ISHLT grade 0 (54.4%) and declined with advancing ISHLT grade (grade 1 43.9% and grade ≥2 1.8%). Sensitivity of MCE for clinically-defined CAV exceeded ICA for ISHLT grade 0 (56.8% vs. 27.0%), whereas ICA outperformed MCE for more advanced disease (ISHLT grade 1: 85.4% vs. 46.3%; ISHLT grade ≥2: 100% vs. 83.3%). Overall sensitivity and specificity were 60.7% and 87.2% for ICA and 53.6% and 76.5% for MCE. AUC was 0.73 (95% CI 0.65–0.81) for ICA and 0.65 (95% CI 0.56–0.74) for MCE (p=0.19).
Conclusions
While ICA remains the standard for defining advanced CAV, it frequently misses early, clinically relevant disease. At our institution, MCE demonstrated higher sensitivity for CAV in patients with angiographically normal coronaries, indicating its value in detecting impaired flow reserve and microvascular disease beyond angiographically defined flow obstruction. MCE enhances CAV detection and risk stratification beyond angiography alone, supporting its integration as a complementary tool in routine post-transplant surveillance for more proactive graft preservation.Table 1.Perfusion Modality PerformanceFor image description, please refer to the figure legend and surrounding text.Figure 1.ICA and MCE ROC curvesFor image description, please refer to the figure legend and surrounding text.