Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy

Background The progressive risk of graft failure in pediatric heart transplantation (PHT) necessitates close surveillance for rejection and coronary allograft vasculopathy (CAV). The current gold standard of surveillance via invasive coronary angiography is costly, imperfect and associated with complications. Our goal was to assess the safety and feasibility of a comprehensive multi-parametric CMR protocol with regadenoson stress perfusion in PHT and evaluate for associations with clinical history of rejection and CAV. Methods We performed a retrospective review of 26 PHT recipients who underwent stress CMR with tissue characterization and compared with 18 age-matched healthy controls. CMR protocol included myocardial T2, T1 and extracellular volume (ECV) mapping, late gadolinium enhancement (LGE), qualitative and semi-quantitative stress perfusion (myocardial perfusion reserve index; MPRI) and strain imaging. Clinical, demographics, rejection score and CAV history were recorded and correlated with CMR parameters. Results Mean age at transplant was 9.3 ± 5.5 years and median duration since transplant was 5.1 years (IQR 7.5 years). One patient had active rejection at the time of CMR, 11/26 (42%) had CAV 1 and 1/26 (4%) had CAV 2. Biventricular volumes were smaller and cardiac output higher in PHT vs. healthy controls. Global T1 (1053 ± 42 ms vs 986 ± 42 ms; p < 0.001) and ECV (26.5 ± 4.0% vs 24.0 ± 2.7%; p = 0.017) were higher in PHT compared to helathy controls. Significant relationships between changes in myocardial tissue structure and function were noted in PHT: increased T2 correlated with reduced LVEF (r = − 0.57, p = 0.005), reduced global circumferential strain (r = − 0.73, p < 0.001) and reduced global longitudinal strain (r = − 0.49, p = 0.03). In addition, significant relationships were noted between higher rejection score and global T1 (r = 0.38, p = 0.05), T2 (r = 0.39, p = 0.058) and ECV (r = 0.68, p < 0.001). The presence of even low-grade CAV was associated with higher global T1, global ECV and maximum segmental T2. No major side effects were noted with stress testing. MPRI was analyzed with good interobserver reliability and was lower in PHT compared to healthy controls (0.69 ± − 0.21 vs 0.94 ± 0.22; p < 0.001). Conclusion In a PHT population with low incidence of rejection or high-grade CAV, CMR demonstrates important differences in myocardial structure, function and perfusion compared to age-matched healthy controls. Regadenoson stress perfusion CMR could be safely and reliably performed. Increasing T2 values were associated with worsening left ventricular function and increasing T1/ECV values were associated with rejection history and low-grade CAV. These findings warrant larger prospective studies to further define the role of CMR in PHT graft surveillance.

Regadenoson stress CMR: safety, feasibility and hemodynamic response

Background and objectives The use of regadenoson for stress cardiac magnetic resonance (CMR) has potential advantages over other vasodilators. We sought to evaluate the safety, feasibility and hemodynamic response (heart rate and blood pressure) of regadenoson in an unselected population undergoing stress CMR for clinical work-up. Methods A total of 603 regadenoson stress CMR clinical examinations performed between May 2017 and May 2020 in our institution were retrospectively reviewed. Studies were performed using a conventional stress/rest CMR protocol with a 1.5T MRI scanner. A fixed dose of 5 ml of regadenoson was employed as stressor. As part of the protocol, 200 mg of theophylline was administered between stress and rest acquisitions to reverse the vasodilator effect of regadenoson. Adverse events, clinical symptoms, and hemodynamic response were assessed. Results In our cohort, no severe adverse events requiring hospitalization were observed, and only 5 adverse events were reported (0.83%). Only two patients (0.3%) did not complete the test due to adverse events or symptoms related to regadenoson administration (one case presented severe hypotension; the other presented unbearable chest pain). There were no cases of bronchospasm, stress-induced arrhythmia or death. Over half of patients reported mild symptoms after drug administration (52%, n=314), more frequently dyspnea (19%, n=112), chest pain (18%, n=106) and flushing (6%, n=34). All symptoms resolved after theophylline administration. Overall, an increase in heart rate (mean increase and (standard deviation) = 24 (12.6) bpm and a mild decrease in systolic (−8.2 (17.1) mmHg) and diastolic (−4.9 (10.2) mmHg) blood pressure were observed as response to regadenoson. A blunted heart rate response was observed in elderly (p&lt;0.01), diabetic (p&lt;0.01) and obese (p=0.01) patients. Only 46 patients (7.8%) did not show tachycardization response. Conclusions The use of regadenoson in stress CMR proved to be safe and feasible in the vast majority of patients. Adverse events were not frequent with regadenoson and symptoms were transient and well tolerated, while premature ending of the test related to drug administration was very rare. FUNDunding Acknowledgement Type of funding sources: None. Hemodynamic response

Cardiac stress T1-mapping response and extracellular volume stability of MOLLI-based T1-mapping methods

Stress and rest T1-mapping may assess for myocardial ischemia and extracellular volume (ECV). However, the stress T1 response is method-dependent, and underestimation may lead to misdiagnosis. Further, ECV quantification may be affected by time, as well as the number and dosage of gadolinium (Gd) contrast administered. We compared two commonly available T1-mapping approaches in their stress T1 response and ECV measurement stability. Healthy subjects (n = 10, 50% female, 35 ± 8 years) underwent regadenoson stress CMR (1.5 T) on two separate days. Prototype ShMOLLI 5(1)1(1)1 sequence was used to acquire consecutive mid-ventricular T1-maps at rest, stress and post-Gd contrast to track the T1 time evolution. For comparison, standard MOLLI sequences were used: MOLLI 5(3)3 Low (256 matrix) & High (192 matrix) Heart Rate (HR) to acquire rest and stress T1-maps, and MOLLI 4(1)3(1)2 Low & High HR for post-contrast T1-maps. Stress and rest myocardial blood flow (MBF) maps were acquired after IV Gd contrast (0.05 mmol/kg each). Stress T1 reactivity (delta T1) was defined as the relative percentage increase in native T1 between rest and stress. Myocardial T1 values for delta T1 (dT1) and ECV were calculated. Residuals from the identified time dependencies were used to assess intra-method variability. ShMOLLI achieved a greater stress T1 response compared to MOLLI Low and High HR (peak dT1 = 6.4 ± 1.7% vs. 4.8 ± 1.3% vs. 3.8 ± 1.0%, respectively; both p < 0.0001). ShMOLLI dT1 correlated strongly with stress MBF (r = 0.77, p < 0.001), compared to MOLLI Low HR (r = 0.65, p < 0.01) and MOLLI High HR (r = 0.43, p = 0.07). ShMOLLI ECV was more stable to gadolinium dose with less time drift (0.006–0.04% per minute) than MOLLI variants. Overall, ShMOLLI demonstrated less intra-individual variability than MOLLI variants for stress T1 and ECV quantification. Power calculations indicate up to a fourfold (stress T1) and 7.5-fold (ECV) advantage in sample-size reduction using ShMOLLI. Our results indicate that ShMOLLI correlates strongly with increased MBF during regadenoson stress and achieves a significantly higher stress T1 response, greater effect size, and greater ECV measurement stability compared with the MOLLI variants tested.