Abstract
Background
Cardiovascular magnetic resonance with myocardial stress perfusion (stress CMR) is a non-invasive technique that offers an assessment of myocardial function, perfusion, and viability. Regadenoson is a selective cardiac adenosine A2 receptor agonist with fewer side effects than adenosine and a favorable safety profile in older pediatric heart transplant recipients (PHTR). There are limited studies evaluating the hemodynamic response of regadenoson in pediatric patients under general anesthesia (GA).
Methods
We reviewed our experience with regadenoson stress CMR in PHTR under GA from 2020–2024 and compared to a non-GA group of PHTR who underwent regadenoson stress CMR from 2015–2022. Demographic and clinical data were recorded. Hemodynamic response and adverse events were reviewed. CMRs were reviewed for perfusion abnormalities and semi-quantitative analysis was performed using myocardial perfusion reserve index (MPRI).
Results
Forty-six PHTR underwent 53 stress CMRs under GA over the study period (mean age 7.8 years; range 3–19 years). All patients received endotracheal intubation and sevoflurane and were monitored during and after regadenoson administration per institutional protocol. Heart rate (HR) prior to regadenoson administration was 84 ± 12 beats/min with a peak of 109 ± 14 beats/min and average mean blood pressure (BP) was 63 ± 12 mmHg with a nadir of 45 ± 8 mmHg. Transient hypotension was observed in 33 (77%) scans, which resolved with phenylephrine. There were no other adverse events. Phenylephrine was used in 48 CMRs (91%) for BP support at the discretion of anesthesia. Thirty-eight PHTR underwent 48 stress CMRs without sedation. CMRs were matched by time since transplant. The non-GA group was significantly older (mean age 15.8 years; p<0.001). GA patients had a larger percent decrease in mean BP compared to non-GA patients (27 ± 17% vs 15 ± 17%; p<0.001) with no difference in HR change. There were no significant differences in rates of qualitative perfusion defects, (11% vs 4%, p = 0.18), late gadolinium enhancement or MPRI values between the two groups.
Conclusion
Regadenoson stress CMR is safe and feasible in PHTR under GA. While hypotension was frequently seen, it improved in all cases with phenylephrine. Semi-quantitative myocardial perfusion analysis by MPRI is feasible in these young patients, however further studies are needed to assess its clinical utility in this population.
Keywords: Stress CMR, Pediatric CMR, Regadenoson, Pediatric heart transplant
Graphical abstract
1. Background
Myocardial stress perfusion cardiovascular magnetic resonance (CMR) is a non-invasive technique that offers qualitative and quantitative assessment of myocardial function, perfusion, and viability [1]. While adenosine is a common coronary vasodilatory agent used for stress CMR, regadenoson is emerging as the preferred agent in children due to its longer half-life and selective adenosine A2a receptor activity in children. In adults, stress CMR with regadenoson has been shown to have similar vasodilator efficacy to dipyridamole with superior performance in assessing myocardial blood flow and perfusion reserve in patients with coronary artery disease [2]. Several studies have shown that regadenoson is safe and well-tolerated in pediatric patients with congenital heart disease, both with and without sedation [1], [3], [4], [5], [6], [7].
More recently, qualitative and quantitative myocardial perfusion assessment with regadenoson stress CMR has been shown to be useful in detecting coronary allograft vasculopathy (CAV) in adult heart transplant patients [8]. Regadenoson has many benefits as a stress agent, especially in the pediatric heart transplant recipients (PHTR), due to its significantly decreased affinity for the adenosine A1 receptor, which is associated with AV block. In addition, the longer half-life of regadenoson compared to adenosine (t1/2 = 2 h vs. t1/2 < 10 s, respectively) allows for a single bolus injection that requires only one intravenous access site for both stress agent and contrast [1], [9]. A previous study from our center demonstrated the safety and feasibility of regadenoson stress perfusion CMR in older PHTR without general anesthesia (GA) [10]. However, as younger patients, such as infants and toddlers, undergo cardiac transplantation at an earlier age, GA is often required for successful CMR [11]. There are currently no studies evaluating the feasibility and safety of regadenoson stress perfusion CMR under GA within the PHTR population.
As the cardiorespiratory response in PHTR differs compared to healthy controls [12], we aimed to review our single-center experience with use of regadenoson for stress CMR in PHTR under GA and compared them to PHTR without sedation. We also aimed to evaluate the feasibility of semi-quantitative assessment of perfusion in these patients via the myocardial perfusion reserve index (MPRI).
2. Methods
We conducted a single-center retrospective review of all PHTR who underwent regadenoson stress CMR under GA from March 2020 to April 2024 (GA group). This GA group was compared to a non-GA group of PHTR who underwent regadenoson stress CMR from 2015–2022. The distribution of time of CMR since time of transplant was obtained for the GA group and this was used to match patients in the non-GA group. Demographic and clinical data consisting of patient age, gender, weight, body surface area (BSA), self-reported race and ethnicity, history of CAV or rejection, and left-ventricular end-diastolic pressure were collected from clinical documentation or most recent cardiac catheterization reports. The study underwent IRB approval. An ethics committee was not needed as these studies were obtained as part of the clinical protocol of the transplant program.
2.1 Anesthesia and monitoring
All patients in the GA group were anesthetized and monitored according to an institutional protocol (Fig. 1). A pre-procedural baseline ECG was obtained in the pre-operative area. Patients received general endotracheal anesthesia with sevoflurane (0.5–1 minimum alveolar concentration) and neuromuscular blockade with rocuronium to allow for breath holds when required by imaging sequence. Prior to regadenoson administration, the patient was given 100% inspired oxygen as a standard to maximize oxygen delivery. Regadenoson was administered as a bolus of 8 mcg/kg (maximum 400 mcg), followed by reversal with aminophylline 5 mg/kg/dose (maximum 75 mg) after perfusion imaging was completed. Heart rate (HR) and blood pressure (BP) were monitored and documented every 1 min during the stress portion of the study. BP was monitored via arterial line or non-invasive cuff based on anesthesiologist preference. In addition, phenylephrine was used as a bolus or infusion based on anesthesiologist's preference to maintain mean BP within 10–15% of baseline and to treat episodes of hypotension. Treatment with phenylephrine maintained homeostatic hemodynamic conditions during imaging and regadenoson while under GA. Following imaging, the patient was transferred to the post-anesthesia care unit (PACU) for recovery. Vital signs were monitored every 15 min until the patient met the following criteria for discharge: stable vital signs, easily arousable, and maintaining a patent airway.
Fig. 1.
Stress CMR institutional protocol. 2 C two chamber, 4 C four chamber, 3 C three chamber, MOLLI Modified Look-locker inversion recovery, SAX short axis, ECV extracellular volume, GETA general endotracheal tube anesthesia, LGE late gadolinium enhancement
Patients in the non-GA group were monitored according to a previously published institutional protocol [4]. Vital signs were evaluated prior to administration of regadenoson. HR and BP were monitored every 1 min for 5 min, every 5 min for the next 20 min, and then every 10–15 min until 1 h after regadenoson administration.
The dose of regadenoson and aminophylline were recorded. Adverse events including bronchospasm, arrhythmia, and hypotension (defined as mean BP decrease of >20% baseline) were reviewed.
2.2 CMR acquisition
CMR was performed on a 1.5T scanner (Aera, Siemens Healthineers, Erlangen, Germany). A comprehensive protocol for structural and functional assessment was performed with addition of stress perfusion imaging utilizing regadenoson (Lexiscan, Astellas Pharma, Northbrook, Illinois), as we described previously (Fig. 1) [4], [9]. Regadenoson was administered and, after a 60–90 s delay to allow the HR to increase and plateau, first-pass contrast-enhanced images were obtained at three short axis levels (basal, mid-ventricular, and apical) with the addition of motion correction (MOCO). Single-shot fast gradient echo sequences were acquired during stress after the intravenous administration of 0.075 mmol/kg of gadobutrol (Gadavist, Bayer Healthcare, Whippany, New Jersey). Image specifications were TR = 197.5 ms TE = 1.1 ms, inversion time (TI) 120 ms, flip angle = 15°, slice thickness = 6–8 mm, inplane resolution = 1 × 1 mm2. After image acquisition, intravenous aminophylline was given to reverse the effects of regadenoson. Another 0.075 mmol/kg of gadobutrol was administered prior to rest perfusion imaging for a total of 0.15 mmol/kg of gadolinium-based contrast agent for LGE. Gadolinium was injected at a rate of 4 mL/sec.
2.3 CMR image analysis
Interpretation of first-pass perfusion images (both MOCO and raw images) for assessment of myocardial perfusion was independently performed by one pediatric cardiologist (9 years of experience) and one pediatric radiologist (14 years of experience) who were blinded to the clinical report (S.L. and A.P.). The images were qualitatively evaluated for any areas of hypointensity along the subendocardium in a coronary distribution and reported using the American Heart Association (AHA) myocardial segmental model [13]. Hypoperfusion was scored as 0 (normal), 1 (equivocal), or 2 (positive for subendocardial ischemia) based on the CE-MARC trial [14]. Abnormalities were called positive if the hypointensity was most pronounced 2–3 heartbeats after the left-ventricular cavity was maximally enhanced with contrast and continued to persist after the contrast washed out of the myocardium. The presence of LGE was identified by visual assessment as areas of increased signal intensity that was seen in orthogonal views. The presence of wall motion abnormalities was also identified by visual assessment.
Semi-quantitative myocardial perfusion assessment was performed by calculating MPRI using commercially available software (Medis Suite 3.0, Medis Medical Imaging Systems Leiden, The Netherlands). To assess the feasibility and reproducibility of MPRI, the endocardial and epicardial borders were manually traced on all frames of the rest and stress motion-corrected images at the mid-ventricular level. The left-ventricular blood pool signal was identified with a region of interest. Segmental time signal intensity (TSI) curves were generated at rest and stress states. The maximum upslope was defined as the maximum rate of signal intensity increase per time. The relative upslope was calculated by dividing the maximum upslope of the segmental TSI curve by the maximum upslope of the blood pool TSI curve. The MPRI was calculated as the ratio of the relative upslope of stress and rest for each segment of the mid-ventricular slice. Interobserver variability of the MPRI was calculated for a subset of 10 patients by 2 reviewers (N.D. and N.H.).
2.4 Statistical analysis
Categorical variables are summarized as numbers and percentages. Continuous variables are expressed as means ± standard deviations. The GA and non-GA groups were compared using Mann–Whitney U tests for continuous variables and z-scores for proportions. Interobserver variability was reported using a linear regression model, kappa statistic, and Bland-Altman analysis. Significance was defined as p<0.05.
3. Results
3.1 Study population
Forty-six PHTR underwent 53 regadenoson stress perfusion CMRs under GA during the study period. All patients received endotracheal intubation and sevoflurane for induction. The mean age was 7.8 ± 3.6 years (range 3.4–18.7 years) with a mean weight of 25.4 ± 13.8 kg (range 11.5–74.5 kg) and BSA of 0.91 ± 0.32 kg/m2 (range 0.53–1.94 kg/m2). Patients underwent CMR at a mean of 5.8 ± 3.3 years from transplantation. Average left-ventricular end-diastolic pressure (LVEDP) prior to CMR was 10 ± 2 mmHg. Two patients (4%) had a history of CAV (one with CAV1 and one with CAV2) and three (7%) had a history of rejection in the 6 months prior to CMR. Twenty-two patients (48%) had a baseline ECG abnormality. Twenty had some form of right-ventricular conduction delay (incomplete right bundle branch block [IRBBB] or right bundle branch block [RBBB]), three had prolonged QTc, and one had Wolff-Parkinson-White.
Thirty-eight PHTR matched by time since transplant underwent 48 regadenoson stress perfusion CMRs without anesthesia. The non-GA group was significantly older (mean age 15.8 ± 3.8 years; p<0.001) with a larger BSA (1.6 ± 0.4 kg/m2; p<0.001) as expected. As this group was significantly older than the GA group, there were less CMRs and less patients that could be matched using time-since-transplant. There were no other significant differences in demographic data between the two groups. Patients underwent CMR at mean 5.9 ± 3.5 years from transplantation. Average LVEDP was 11 ± 4 mmHg. Six patients (16%) had a history of CAV (4 with CAV1 and 2 with CAV2) and 9 (24%) had a history of rejection in the 6 months prior to CMR. Twenty patients (53%) had a baseline ECG abnormality. Seventeen had some form of right-ventricular conduction delay (RVCD) (IRBBB, RBBB, or RVCD) of which two also had first degree atrioventricular block (AVB). Two had isolated first degree AVB and one had intraventricular conduction delay. A summary of the demographic data of the GA and non-GA groups is demonstrated in Table 1.
Table 1.
Demographic and clinical data.
| GA (N = 53) | Non-GA (N = 48) | p-value | |
|---|---|---|---|
| Sex, female | 19 (41%) (N=46) |
21 (55%) (N=38) |
0.20 |
| Age at CMR (years) | 7.8 ± 3.6 | 15.8 ± 3.8 | <0.001 |
| Weight (kg) | 25.4 ± 13.8 | 58.8 ± 23.4 | <0.001 |
| BSA (kg/m2) | 0.91 ± 0.32 | 1.6 ± 0.4 | <0.001 |
| Time from transplant to CMR (years) | 5.8 ± 3.4 | 5.9 ± 3.5 | 0.85 |
| Baseline ECG Abnormality | 24/53 (45%) | 26/48 (54%) | 0.37 |
Values reported as number and percentage or mean ± standard deviation. p-value <0.05 (bolded) is significant.
BSA body surface area, CMR cardiovascular magnetic resonance, ECG electrocardiogram, GA general anesthesia
*Data is reported by CMR sample except for sex which is reported by patient sample
3.2 Hemodynamic response
Regadenoson was administered at a dose of 8 mcg/kg (maximum 400 mcg) except for three patients who received 6 mcg/kg in the early period of our stress CMR protocol. The average baseline HR in the GA group rose from 84 ± 12 beats per minute (bpm) to 109 ± 14 bpm. The average mean BP decreased from 63 ± 12 mmHg to 45 ± 8 mm Hg and the average diastolic BP decreased from 48 ± 11 mmHg to 35 ± 7 mm Hg. Of 53 CMRs, transient hypotension (defined as a mean BP decrease >20% from baseline) occurred during 33 (77%) scans within the first 2 min after regadenoson, which resolved with phenylephrine. There were no other adverse events noted. Overall, phenylephrine was administered in 48 of 53 CMRs (91%) for BP support at the discretion of the anesthesia team, as described above.
In non-GA patients, the average HR rose from 89 ± 12 bpm to 118 ± 12 bpm and the average mean BP decreased from 87 ± 13 mm Hg to 73 ± 15 mm Hg. The average diastolic BP decreased from 73 ± 12 mm Hg to 55 ± 14 mm Hg. HR and mean BP and diastolic BP changes in GA and non-GA patients are shown in Fig. 2.
Fig. 3.
Assessment of myocardial perfusion defect in a 5-year-old patient demonstrating (a) homogenous myocardial contrast enhancement at rest and (b) area of subendocardial hypointensity in the mid inferoseptum and inferior wall (arrow) at stress
Fig. 2.
Heart rate (HR), mean blood pressure (MBP), and diastolic blood pressure (DBP) during regadenoson stress perfusion cardiac MRI in GA (top) and non-GA (bottom). Regadenoson administered at t = 0. Values are expressed as mean and error bars as standard deviation. HR heart rate, MBP mean blood pressure, DBP diastolic blood pressure
While the non-GA group also experienced a decrease in mean BP, the GA group had a larger percent decrease in BP (27 ± 17% vs 15 ± 17%; p<0.00001). There was no significant difference in percent change in HR between the two groups. Additionally, there were no significant differences in time to recovery of BP (6 vs 8 min; p = 0.9) and HR (9 vs 11 min (p = 0.4) between the GA and non-GA groups, respectively.
3.3 CMR data
All images were deemed of diagnostic quality for interpretation. No scans were terminated prematurely. Mean left-ventricular ejection fraction, left-ventricular end-diastolic volume and right-ventricular end-diastolic volume were normal with no significant difference between the two groups. Mean right-ventricular ejection fraction (RVEF) was normal with non-GA patients having a higher RVEF than GA patients. All CMR data is shown in Table 2.
Table 2.
CMR data.
| GA (N = 53) | Non-GA (N = 48) | p-value | |
|---|---|---|---|
| LVEF (%) | 59 ± 5 | 60 ± 5 | 0.24 |
| LVEDVi (mL/m2) | 73 ± 13 | 76 ± 15 | 0.36 |
| RVEF (%) | 54 ± 6 | 58 ± 6 | 0.01 |
| RVEDVi (mL/m2) | 75 ± 15 | 75 ± 15 | 0.80 |
| Rest Perfusion Defect | 5/53 (9%) | 1/48 (2%) | 0.94 |
| Stress Perfusion Defect | 6/53 (11%) | 2/48 (4%) | 0.18 |
| Wall Motion Abnormality | 0% | 3/47 (6%)* | 0.06 |
| LGE | 15/53 (28%) | 16/48 (33%) | 0.58 |
| MPRI | 1.55 ± 0.46 | 1.35 ± 0.41 | 0.05 |
Values reported as number and percentage or mean ± standard deviation. p-value <0.05 (bolded) is significant
CMR cardiovascular magnetic resonance, GA general anesthesia, LGE late gadolinium enhancement, LVEDVi indexed left-ventricular end-diastolic volume, LVEF left-ventricular ejection fraction, MPRI myocardial perfusion reserve index, RVEDVi indexed right-ventricular end-diastolic volume, RVEF right-ventricular ejection fraction
*One patient had gating artifact from ectopy so unable to quantify function or wall motion
3.4 Stress perfusion analysis
Stress perfusion was performed on all GA and non-GA CMRs. There was substantial interobserver agreement for positive stress perfusion defects (kappa = 0.672). On independent review, five studies were called positive or equivocal by a cardiologist reviewer and eight studies were called positive or equivocal by a radiologist reviewer. Discrepant studies were reviewed for consensus. In the GA group, 6/53 (11%) CMRs showed a stress perfusion defect. None of these correlated with wall motion abnormalities. Fifteen CMRs (28%) had LGE (Fig. 4) of which 3/15 (20%) correlated with a stress perfusion defect. LGE was located focally in the hingepoint in 11/15, septal wall in 1/15, and inferior wall in 1/15. Two CMRs had diffuse LGE with one of these also having lateral wall enhancement. Among the non-GA CMRs, 2/48 (4%) showed a stress perfusion defect. While 3/47 (6%) studies had wall motion abnormalities, none of these correlated with perfusion defects. Sixteen (16/48; 33%) had LGE of which 1/16 (6%) correlated with a perfusion defect. LGE was located focally in the hingepoint in 9/16, lateral wall in 5/16, and basal anterior wall in 1/16. One CMR had diffuse enhancement.
Fig. 4.
Assessment of late gadolinium enhancement in a 6-year-old patient demonstrating extensive area of mid-myocardial enhancement along the inferoseptum from base to apex (arrow) in a (a) short axis image and (B) 4-chamber image
The mid-ventricular MPRI of the GA CMRs was not significantly different from the non-GA. There was no significant interobserver variability (n = 10, r2 = 0.89, p<0.0001) in the MPRI measurement on GA CMRs (Fig. 5). Bland–Altman analysis demonstrates a small discrepancy between observers (mean bias= −0.053 (−0.27 to 0.17) (Fig. 6).
Fig. 5.
Interobserver variability for MPRI. MPRI myocardial perfusion reserve index
Fig. 6.
Bland–Altman plot for myocardial perfusion reserve index
4. Discussion
Our study demonstrates that regadenoson stress perfusion CMR in PHTR under GA is safe and well-tolerated. Transient but mild hypotension within the first 2 min after regadenoson administration was frequently observed in GA patients, with all cases improving after administration of phenylephrine. There were no other adverse events, including arrhythmias, significant myocardial ischemia, as noted by the absence of regional wall motion abnormalities, ECG changes, or cardiac arrest. These findings are similar to those previously reported in other pediatric populations [1], [5], [6], [7].
As seen in previous studies, HR increased in all patients with regadenoson [2], [3], [4], [5], [6], [7]. This, in addition to the decrease in BP, suggests that regadenoson has significant vasodilatory effects, and thus can be used for evaluation of suspected fixed coronary artery obstruction. A previous study from our group demonstrated that inducible subendocardial defects were noted in 25% of PHT patients with known CAV and overlapped with CAV coronary territory in all positive findings [10]. As GA is commonly used in younger patients to facilitate cooperation with the exam, the safety and feasibility of regadenoson for these patients allows surveillance at younger ages.
Regadenoson is a selective cardiac adenosine A2a receptor agonist that has few adverse events and is well tolerated in older PHTR [10]. When compared to adenosine, regadenoson has similar coronary vasodilatory effects with fewer side effects and has technical advantages for utilization in pediatric CMR [1], [2]. While there were no instances of arrhythmia or bronchospasm, our PHTR under GA experienced a larger decrease in BP compared to the non-GA PHTR. Doan et al. also reported similar findings in patients with Kawasaki disease, with 28% of sedated patients experiencing hypotension compared to 4% of non-sedated patients [5]. In our study, PHTR under GA were also younger with a smaller weight and BSA. Hypotension in those that were sedated is likely related to vasodilatory effects of anesthetic volatile agents in younger and smaller patients versus their status as PHTR. Regadenoson was otherwise well tolerated, and all scans were completed without complication.
All patients received sevoflurane for anesthesia. Sevoflurane is a halogenated volatile anesthetic that decreases systemic vascular resistance and sympathetic nervous activity. While volatile anesthetics increase HR and decrease BP, sevoflurane has been shown to have less impact on HR in children. Sevoflurane is known to decrease BP, though the degree of hypotension is variable [15]. Therefore, while we found a mild effect from regadenoson on BP in the non-GA group, this effect may have been enhanced by addition of sevoflurane in the GA group.
Additionally, phenylephrine was regularly utilized to mitigate and treat regadenoson-induced hypotension. Some studies have demonstrated that phenylephrine has a coronary vasodilatory effect in both controls and transplant recipients and also increases coronary blood flow [16]. This may enhance the effectiveness of the perfusion test given its coronary vasodilator properties. There may also be an additional benefit of phenylephrine in anesthetized patients as it can increase cardiac output through increased preload in these patients with sevoflurane-induced hypotension [17].
Stress CMR is used for transplant surveillance in our institution, and routine baseline CMRs are done 1–2 years post-transplant. Our study found a low incidence of perfusion abnormalities in our GA and non-GA groups. Clinically this group had a low incidence of CAV, consistent with our CMR findings. Since stress CMR is more relevant for the assessment of CAV later on post-transplant, it is helpful to have baseline perfusion data in these patients. Interestingly, we found 15 CMRs which showed LGE. The pattern of LGE was generally non-ischemic and did not significantly correlate with perfusion defects. In a study by Lawson et al., they found that greater time since transplant was a risk factor for LGE [18]. This is supported by our findings that despite a young median age of the GA group, there were still many patients that had LGE. This may be related to the presence of microvascular dysfunction, which may not be visualized well by stress perfusion CMR or cine X-ray angiography. Further investigation in this area is warranted.
Qualitative assessment of perfusion abnormalities demonstrated modest interobserver agreement. However, many studies were called equivocal, which may point to the challenges of assessing perfusion defects qualitatively in smaller, younger patients. Therefore, fully quantitative or semi-quantitative assessment via MPRI may be helpful in these patients to provide a more definitive assessment of perfusion. Semi-quantitative analysis of myocardial perfusion with MPRI has been used for detection of perfusion abnormalities in patients with coronary artery disease and may be the preferred technique for evaluation [4], [19], [20]. Both adult and pediatric studies have demonstrated decreased MPRI in transplant patients compared to controls, in those with and without CAV, suggesting that MPRI is likely abnormal in transplant patients, and this may be multifactorial [4], [8], [10], [21]. Our study demonstrated that MPRI was feasible and reproducible to measure in smaller PHT patients under GA with good interobserver reliability in this measurement. However, due to the low incidence of perfusion abnormalities on CMR, we were unable to evaluate for associated clinical significance.
5. Limitations
Limitations of this study include the retrospective nature and limited sample size. It is important to note that the diastolic BPs in the two groups were different due to many factors, which may also influence the differences in myocardial blood flow. Prior to the administration of regadenoson, the patients were given 100% inspired oxygen to maximize myocardial oxygen delivery. While this increases oxygen delivery, it may cause a degree of microvascular vasoconstriction. Though the patients were at steady state with oxygen delivery during imaging at stress and rest, it is difficult to determine what effect this may have had on perfusion. In addition, semi-quantitative analysis remains challenging in smaller pediatric patients with higher HRs and was performed only on the mid-ventricular segments. In addition, our institutional protocol for stress CMR involves stress-first perfusion (rather than rest-first perfusion) using regadenoson. While studies have shown that regadenoson with aminophylline reversal can be used similarly to adenosine for coronary flow reserve measurements, there are also studies that show differences in MPRI at true rest versus recovery as a substitute for rest [22], [23]. There also are no reference standards at this time for MPRI in pediatric patients. Therefore, the clinical significance of the value of MPRI and difference in MPRI between the two groups remains unclear. Given the small number of perfusion defects and patients with a history of CAV, as well as the lack of a healthy control group, our study was limited in assessing efficacy.
6. Conclusions
In conclusion, regadenoson stress CMR is safe and feasible in pediatric transplant patients under GA. While hypotension was noted frequently, it occurred predictably within 2 min after administration of regadenoson and improved in all cases with a standardized protocol including close monitoring and prophylactic use of phenylephrine. Therefore, we recommend close collaboration with anesthesia and the capability of using phenylephrine for BP management in these patients. We also found that semi-quantitative analysis using MPRI was feasible and reproducible in these patients and future studies are needed to assess the clinical significance of these findings.
Funding
Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL117888.
Author contributions
Husain Nazia: Writing – review & editing, Supervision, Methodology, Formal analysis, Conceptualization. Popescu Andrada: Writing – review & editing, Formal analysis. Magnetta Defne: Writing – review & editing. Das Nikkan: Writing – original draft, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Vu Eric L: Writing – review & editing, Formal analysis, Data curation. Lee Simon: Writing – review & editing, Supervision, Methodology, Formal analysis, Conceptualization. Rigsby Cynthia K: Writing – review & editing. Robinson Joshua D: Writing – review & editing.
Declaration of competing interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Availability of data and materials
The data underlying this article will be shared on reasonable request to the corresponding author.
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Data Availability Statement
The data underlying this article will be shared on reasonable request to the corresponding author.