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Background Multiple studies in adult patients suggest that tissue mapping performed by cardiovascular magnetic resonance (CMR) has excellent diagnostic accuracy in acute myocarditis, however, these techniques have not been studied in depth in children. Methods CMR data on 23 consecutive pediatric patients from 2014 to 2017 with a clinical diagnosis of acute myocarditis were retrospectively analyzed and compared to 39 healthy controls. The CMR protocol included native T1, T2, and extracellular volume fraction (ECV) in addition to standard Lake Louise Criteria (LLC) parameters on a 1.5 T scanner. Results Mean global values for novel mapping parameters were significantly elevated in patients with clinically suspected acute myocarditis compared to controls, with native T1 1098 ± 77 vs 990 ± 34 ms, T2 52.8 ± 4.6 ms vs 46.7 ± 2.6 ms, and ECV 29.8 ± 5.1% vs 23.3 ± 2.6% (all p -values < 0.001). Ideal cutoff values were generated using corresponding ROC curves and were for global T1 1015 ms (AUC 0.936, sensitivity 91%, specificity 86%), for global T2 48.5 ms (AUC 0.908, sensitivity 91%, specificity 74%); and for ECV 25.9% (AUC 0.918, sensitivity 86%, specificity 89%). While the diagnostic yield of the LLC was 57% (13/23) in our patient cohort, 70% (7/10) of patients missed by the LLC demonstrated abnormalities across all three global mapping parameters (native T1, T2, and ECV) and another 20% (2/10) of patients demonstrated at least one abnormal mapping value. Conclusions Similar to findings in adults, pediatric patients with acute myocarditis demonstrate abnormal CMR tissue mapping values compared to controls. Furthermore, we found CMR parametric mapping techniques measurably increased CMR diagnostic yield when compared with conventional LLC alone, providing additional sensitivity and specificity compared to historical references. Routine integration of these techniques into imaging protocols may aid diagnosis in children.

Background Cardiac evaluations, including cardiovascular magnetic resonance (CMR) imaging and biomarker results, are needed in children during mid-term recovery after infection with SARS-CoV-2. The incidence of CMR abnormalities 1–3 months after recovery is over 50% in older adults and has ranged between 1 and 15% in college athletes. Abnormal cardiac biomarkers are common in adults, even during recovery. Methods We performed CMR imaging in a prospectively-recruited pediatric cohort recovered from COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We obtained CMR data and serum biomarkers. We compared these results to age-matched control patients, imaged prior to the SARS-CoV-2 pandemic. Results CMR was performed in 17 children (13.9 years, all ≤ 18 years) and 29 age-matched control patients without SARS-CoV-2 infection. Cases were recruited with symptomatic COVID-19 (11/17, 65%) or MIS-C (6/17, 35%) and studied an average of 2 months after diagnosis. All COVID-19 patients had been symptomatic with fever (73%), vomiting/diarrhea (64%), or breathing difficulty (55%) during infection. Left ventricular and right ventricular ejection fractions were indistinguishable between cases and controls (p = 0.66 and 0.70, respectively). Mean native global T1, global T2 values and segmental T2 maximum values were also not statistically different from control patients (p ≥ 0.06 for each). NT-proBNP and troponin levels were normal in all children. Conclusions Children prospectively recruited following SARS-CoV-2 infection had normal CMR and cardiac biomarker evaluations during mid-term recovery. Trial Registration Not applicable.

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.

Multiparametric cardiovascular magnetic resonance (CMR) has an emerging role in non-invasive surveillance of pediatric heart transplant recipients (PHTR). Higher myocardial T2, higher extracellular volume fraction (ECV), and late gadolinium enhancement (LGE) have been associated with adverse clinical outcomes in adult heart transplant recipients. The purpose of this study was to investigate the prognostic value of CMR-derived T1 and T2 mapping, ECV, and LGE for clinical outcomes in PHTR. We performed a single-center, retrospective chart review of consecutive, gadolinium-enhanced CMR studies in PHTR over a 7.5-year period, excluding follow-up studies. Standard CMR ventricular volume and function analysis, T1 mapping with ECV, T2 mapping, and LGE assessment were performed. The composite outcome included cardiac death, non-cardiac death, re-transplantation, and cardiac hospitalization. Among 113 PHTR, mean age was 13.0 ± 5.1 years, with 6.0 ± 4.0 years since transplant. The indication for CMR was surveillance in 79%. Mean native T1 was 1050 ± 48 ms, T2 49.2 ± 3.9 ms, and ECV 29.7 ± 4.5%. Left ventricular LGE was present in 37% (42/113) and right ventricular LGE in 3.5% (4/113). The mean follow-up time was 2.3 years and median was 1.4 years. Cardiac death occurred in 2% (2/113), re-transplantation in 4% (4/113), and cardiac hospitalization in 22% (25/113). Non-cardiac death did not occur. Using Kaplan-Meier analysis, high T1 (≥1061 ms), T2 (≥50.0 ms), and ECV (≥31.4%) were each associated with decreased freedom from the composite outcome in follow-up. In univariable Cox regression analyses, high T1 was associated with increased risk of the composite outcome (hazard ratios [HR] 4.0, 95% confidence interval [CI] 1.7–9.2, p = 0.001), as were high T2 (HR 2.8, 95% CI 1.1–7.1, p = 0.026), and high ECV (HR 3.5, 95% CI 1.5–8.1, p = 0.004). T1 and T2 mapping are associated with early differences in adverse cardiac events in PHTR. These data suggest a role for a multicenter study with a longer follow-up duration. [Display omitted]

Background Doppler echocardiography (echo) is the reference standard for blood flow velocity analysis, and two-dimensional (2-D) phase-contrast magnetic resonance imaging (MRI) is considered the reference standard for quantitative blood flow assessment. However, both clinical standard-of-care techniques are limited by 2-D acquisitions and single-direction velocity encoding and may make them inadequate to assess the complex three-dimensional hemodynamics seen in congenital heart disease. Four-dimensional flow MRI (4-D flow) enables qualitative and quantitative analysis of complex blood flow in the heart and great arteries. Objectives The objectives of this study are to compare 4-D flow with 2-D phase-contrast MRI for quantification of aortic and pulmonary flow and to evaluate the advantage of 4-D flow-based volumetric flow analysis compared to 2-D phase-contrast MRI and echo for peak velocity assessment in children and young adults. Materials and methods Two-dimensional phase-contrast MRI of the aortic root, main pulmonary artery (MPA), and right and left pulmonary arteries (RPA, LPA) and 4-D flow with volumetric coverage of the aorta and pulmonary arteries were performed in 50 patients (mean age: 13.1 ± 6.4 years). Four-dimensional flow analyses included calculation of net flow and regurgitant fraction with 4-D flow analysis planes similarly positioned to 2-D planes. In addition, 4-D flow volumetric assessment of aortic root/ascending aorta and MPA peak velocities was performed and compared to 2-D phase-contrast MRI and echo. Results Excellent correlation and agreement were found between 2-D phase-contrast MRI and 4-D flow for net flow ( r  = 0.97, P  < 0.001) and excellent correlation with good agreement was found for regurgitant fraction ( r  = 0.88, P  < 0.001) in all vessels. Two-dimensional phase-contrast MRI significantly underestimated aortic ( P  = 0.032) and MPA ( P  < 0.001) peak velocities compared to echo, while volumetric 4-D flow analysis resulted in higher (aortic: P  = 0.001) or similar (MPA: P  = 0.98) peak velocities relative to echo. Conclusion Excellent flow parameter agreement between 2-D phase-contrast MRI and 4-D flow and the improved volumetric 4-D flow velocity analysis relative to echo suggests that 4-D flow has the potential to become a clinical alternative to 2-D phase-contrast MRI.

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). 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). 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. 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. [Display omitted]

This study aimed to validate respiratory-resolved five-dimensional (5D) flow cardiovascular magnetic resonance (CMR) against real-time two-dimensional (2D) phase-contrast MRI, assess the impact of number of respiratory states, and measure the impact of respiration on hemodynamics in congenital heart disease (CHD) patients. Respiratory-resolved 5D flow MRI-derived net and peak flow measurements were compared to real-time 2D phase-contrast MRI-derived measurements in 10 healthy volunteers. Pulmonary-to-systemic flow ratios (Qp:Qs) were measured in 19 CHD patients and aortopulmonary collateral burden was measured in 5 Fontan patients. Additionally, the impact of number of respiratory states on measured respiratory-driven net flow changes was investigated in 10 healthy volunteers and 19 CHD patients (shunt physiology, n = 11, single ventricle disease [SVD], n = 8). There was good agreement between 5D flow MRI and real-time 2D phase-contrast–derived net and peak flow. Respiratory-driven changes had a good correlation (rho = 0.64, p < 0.001). In healthy volunteers, fewer than four respiratory states reduced measured respiratory-driven flow changes in veins (5.2 mL/cycle, p < 0.001) and arteries (1.7 mL/cycle, p = 0.05). Respiration drove substantial venous net flow changes in SVD (64% change) and shunt patients (57% change). Respiration had significantly greater impact in SVD patients compared to shunt patients in the right and left pulmonary arteries (46% vs 15%, p = 0.003 and 59% vs 20%, p = 0.002). Qp:Qs varied by 37 ± 24% over respiration in SVD patients and 12 ± 20% in shunt patients. Aortopulmonary collateral burden varied by 118 ± 84% over respiration in Fontan patients. The smallest collateral burden was measured during active inspiration in all patients and the greatest burden was during active expiration in four of five patients. Reduced respiratory resolution blunted measured flow changes in the caval veins of shunt and SVD patients (p < 0.005). Respiratory-resolved 5D flow MRI measurements agree with real-time 2D phase contrast. Venous measurements are sensitive to number of respiratory states, whereas arterial measurements are more robust. Respiration has a substantial impact on caval vein flow, Qp:Qs, and collateral burden in CHD patients. [Display omitted]

Blood flow dynamics make it possible to better understand the development of aortopathy and cardiovascular events in patients with Marfan syndrome (MFS). Aortic 3D blood flow characteristics were investigated in relation to aortic geometry in children and adolescents with MFS. Twenty-five MFS patients (age 15.6 ± 4.0 years; 11 females) and 21 healthy controls (age 16.0 ± 2.6 years; 12 females) underwent magnetic resonance angiography and 4D flow CMR for assessment of thoracic aortic size and 3D blood flow velocities. Data analysis included calculation of aortic diameter and BSA-indexed aortic dimensions (Z-score) along the thoracic aorta, 3D mean systolic wall shear stress (WSSmean) in ten aortic segments and assessment of aortic blood flow patterns. Aortic root (root), ascending (AAo) and descending (DAo) aortic size was significantly larger in MFS patients than healthy controls (Root Z-score: 3.56 ± 1.45 vs 0.49 ± 0.78, p < 0.001; AAo Z-score 0.21 ± 0.95 vs −0.54 ± 0.64, p = 0.004; proximal DAo Z-score 2.02 ± 1.60 vs 0.56 ± 0.66, p < 0.001). A regional variation in prevalence and severity of flow patterns (vortex and helix flow patterns) was observed, with the aortic root and the proximal DAo (pDAo) being more frequently affected in MFS. MFS patients had significantly reduced WSSmean in the proximal AAo (pAAo) outer segment (0.65 ± 0.12 vs. 0.73 ± 0.14 Pa, p = 0.029) and pDAo inner segment (0.74 ± 0.17 vs. 0.87 ± 0.21 Pa, p = 0.021), as well as higher WSSmean in the inner segment of the distal AAo (0.94 ± 0.14 vs. 0.84 ± 0.15 Pa, p = 0.036) compared to healthy subjects. An inverse relationship existed between pDAo WSSmean and both pDAo diameter (R = −0.53, p < 0.001) and % diameter change along the pDAo segment (R = −0.64, p < 0.001). MFS children and young adults have altered aortic flow patterns and differences in aortic WSS that were most pronounced in the pAAo and pDAo, segments where aortic dissection or rupture often originate. The presence of vortex flow patterns and abnormal WSS correlated with regional size of the pDAo and are potentially valuable additional markers of disease severity.

Cardiovascular magnetic resonance (CMR) is used to diagnose myocarditis in adults and children based on the original Lake Louise criteria (LLC) and more recently the revised LLC. The major change included in the revised LLC was the incorporation of parametric mapping, which significantly increases the sensitivity and specificity of diagnosis. Subsequently, scientific statements have recommended the use of parametric mapping in the diagnosis of myocarditis in children. However, there are some challenges to parametric mapping that are unique to the pediatric population. Our goal is to characterize clinical CMR and parametric mapping practice patterns for the diagnosis of myocarditis in pediatric centers. The Cardiovascular Magnetic Resonance Evaluation in Return to Athletes for Myocarditis in Coronavirus Disease 2019 and Immunization Consortium (CERAMICi) created a Research Electronic Data Capture (REDCap) survey to evaluate clinical practice patterns for diagnosis of myocarditis in pediatrics. This survey was distributed to the Society for Cardiovascular Magnetic Resonance community. Fifty-nine responses from 51 centers were received, with only one response from each center being utilized. Only 35% (18/51) of centers (37% (14/38) North America, 31% (4/13) international) reported using CMR routinely in all patients with a suspicion of myocarditis. Diagnostic uncertainty was noted as the most important reason for CMR, while cost was noted as the least important consideration. The majority of centers reported using the revised LLC (37/51, 72%) compared to original LLC (7/51, 14%) or a hybrid criteria (6/51, 12%). When looking at the use of parametric mapping, only 5/47 (11%) for T1 mapping and 11/49 (22%) for T2 mapping reported having scanner-specific pediatric normative data. Routine CMR imaging for diagnosis of myocarditis in pediatrics is infrequently performed at surveyed centers despite the focus on a group of non-invasive cardiac imagers. While the majority reported using parametric mapping, few centers reported having pediatric scanner-specific normative data. This highlights an important gap in the utilization of CMR that may aid in the diagnosis of myocardial disease. [Display omitted]

Myocardial stress perfusion magnetic resonance imaging is a non-invasive tool to assess for myocardial ischemia and viability. Pediatric myocardial stress perfusion MRI can be challenging due to multiple intravenous lines, sedation, inadequate breath holding, fast heart rates, and complex anatomy. We performed a retrospective analysis in 39 children to evaluate safety and efficacy of regadenoson, a coronary vasodilator administered via a single intravenous line (6–10 mcg/kg), with respiratory motion correction (MOCO) and semi-quantitative blood flow analysis. Stress response data and adverse events were recorded, and image quality compared between native and MOCO reconstructions, assessing for perfusion deficits. Semi-quantitative analysis compared myocardial perfusion reserve index (MPRI) between patients who had a focal perfusion defect, patients who had undergone an orthotopic heart transplant, and non-transplant patients with no focal defects. Stress perfusion was completed in 38/39 patients (median age 15 years with a 41 ± 27% rise in heart rate (p < 0.005). Fifteen out of thirty-eight had transient minor side effects with no major adverse events. MOCO image quality was better than non-MOCO (4.63 vs. 4.01 at rest, p < 0.005: 4.41 vs. 3.84 at stress, p < 0.005). Reversible perfusion defects were seen in 4/38 patients with lower segmental mean MPRI in the area of the perfusion defect, nearing statistical significance when compared to non-transplant patients with no defects (0.78 ± 0.22 vs. 0.99 ± 0.36, p = 0.07). The global MPRI of the 16 patients who had undergone orthotopic heart transplant was significantly lower than the non-transplant patients (0.75 ± 0.22 vs. 0.92 ± 0.23, p = 0.03). Regadenoson is a safe and effective coronary vasodilator for pediatric stress perfusion MRI with MOCO producing better image quality and allowing for semi-quantitative assessment of perfusion deficits that correlate with qualitative assessment.