Manifold-based denoising for Ferumoxytol-enhanced 3D cardiac cine MRI.

The two-dimensional (2D) cine cardiovascular magnetic resonance (CMR) technique is the reference standard for assessing cardiac function. However, one challenge with 2D cine is that the acquisition time for the whole cine stack is long and requires multiple breath holds, which may not be feasible for pediatric or ill patients. Though single breath-hold multi-slice cine may address the issue, it can only acquire low-resolution images, and hence, affect the accuracy of cardiac function assessment. To address these challenges, a Ferumoxytol-enhanced, free breathing, isotropic high-resolution 3D cine technique was developed. The method produces high-contrast cine images with short acquisition times by using compressed sensing together with a manifold-based method for image denoising. This study included fifteen patients (9.1 $ \pm $ 5.6 yrs.) who were referred for clinical cardiovascular magnetic resonance imaging (MRI) with Ferumoxytol contrast and were prescribed the 3D cine sequence. The data was acquired on a 1.5T scanner. Statistical analysis shows that the manifold-based denoised 3D cine can accurately measure ventricular function with no significant differences when compared to the conventional 2D breath-hold (BH) cine. The multiplanar reconstructed images of the proposed 3D cine method are visually comparable to the golden standard 2D BH cine method in terms of clarity, contrast, and anatomical precision. The proposed method eliminated the need for breath holds, reduced scan times, enabled multiplanar reconstruction within an isotropic data set, and has the potential to be used as an effective tool to access cardiovascular conditions.

Right ventricular longitudinal function is linked to left ventricular filling pressure in patients with repaired tetralogy of fallot.

Experimental data on pulmonary regurgitation has linked right ventricular longitudinal function to left ventricular filling pressure in animals with induced and treated pulmonary regurgitation but this relationship has not been investigated in patients with repaired Tetralogy of Fallot (rToF). The aim of this study was to determine if right ventricular longitudinal function assessed using cardiovascular magnetic resonance (CMR) is associated with left ventricular filling pressure in patients with rToF. A second objective of this study was to determine if direction of septal movement is related to right ventricular pressure load in rToF. Eighteen patients with rToF undergoing CMR and heart catheterization prior to pulmonary valve replacement were retrospectively included and catheter-based pressure measurements were compared with CMR-derived RV regional function. Left ventricular filling pressure was measured as precapillary wedge pressure (PCWP). Longitudinal contribution to RV stroke volume correlated with PCWP (r = 0.48; p = 0.046) but not with RV EF or pulmonary regurgitation. Neither RV longitudinal strain nor TAPSE showed correlation with PCWP. Longitudinal contribution to stroke volume was lower for the RV compared to the LV (49 vs 54%; p = 0.039). Direction of septal movement did not show a correlation with RV end-systolic pressure. Right ventricular longitudinal pumping is associated with left ventricular filling pressure in rToF-patients and this inter-ventricular coupling may explain LV underfilling in patients with pulmonary regurgitation and rToF and may be of value to determine right ventricular dysfunction. RV systolic pressure, however, cannot be assessed from the direction of septal movement, in these patients.

Biventricular Pressure-Volume Loop Assessment Before and After Pulmonary Valve Replacement in Tetralogy of Fallot.

Patients with tetralogy of Fallot (TOF) may undergo pulmonary valve replacement (PVR) after initial full repair. We investigated indices of biventricular function, work and efficiency of TOF patients' using noninvasive pressure-volume (PV) loop analysis on cardiovascular magnetic resonance (CMR) images and compared pre-and post PVR groups. Biventricular segmentations of steady state free precession CMR images were performed using custom validated software (Segment version 2.0 R7067). Brachial cuff pressure estimated left ventricular (LV) systolic pressure. Right ventricular (RV) inputs were obtained from pre-PVR cardiac catheterization data. Biventricular PV loops were then derived using a time-varying elastance model. Twenty seven patients were studied: (22 pre-PVR, 5 post-PVR), mean age of 20±10.5 years and 83% male. RV stroke volume significantly differed before and after PVR (73.2±25 ml vs. 41±10 mL, P =0.01). RV stroke work (SW) and mean external power (MEP) were significantly less post-PVR, but there were no significant differences in the LV hemodynamic indices. TOF patients have reduced RV SW and MEP post-PVR suggesting improved hemodynamics. Noninvasive biventricular PV loop analysis shows potential for integration into standard CMR imaging of TOF and provides hemodynamic data that could influence management decisions.

COVID-19 Vaccination-Associated Myocarditis in Adolescents.

OBJECTIVES: In this study, we aimed to characterize the clinical presentation, short-term prognosis, and myocardial tissue changes as noted on cardiovascular magnetic resonance (CMR) or cardiac MRI in pediatric patients with coronavirus disease 2019 vaccination-associated myocarditis (C-VAM). METHODS: In this retrospective multicenter study across 16 US hospitals, patients <21 years of age with a diagnosis of C-VAM were included and compared with a cohort with multisystem inflammatory syndrome in children. Younger children with C-VAM were compared with older adolescents. RESULTS: Sixty-three patients with a mean age of 15.6 years were included; 92% were male. All had received a messenger RNA vaccine and, except for one, presented after the second dose. Four patients had significant dysrhythmia; 14% had mild left ventricular dysfunction on echocardiography, which resolved on discharge; 88% met the diagnostic CMR Lake Louise criteria for myocarditis. Myocardial injury as evidenced by late gadolinium enhancement on CMR was more prevalent in comparison with multisystem inflammatory syndrome in children. None of the patients required inotropic, mechanical, or circulatory support. There were no deaths. Follow-up data obtained in 86% of patients at a mean of 35 days revealed resolution of symptoms, arrhythmias, and ventricular dysfunction. CONCLUSIONS: Clinical characteristics and early outcomes are similar between the different pediatric age groups in C-VAM. The hospital course is mild, with quick clinical recovery and excellent short-term outcomes. Myocardial injury and edema are noted on CMR. Close follow-up and further studies are needed to understand the long-term implications and mechanism of these myocardial tissue changes.

Management considerations in the adult with surgically modified d-transposition of the great arteries.

Dextro-transposition of the great arteries (D-TGA) has undergone a significant evolution in surgical repair, leading to survivors with vastly different postsurgical anatomy which in turn guides their long-term cardiovascular morbidity and mortality. Atrial switch repair survivors are limited by a right ventricle in the systemic position, arrhythmia and atrial baffles prone to obstruction or leak. Functional assessment of the systemic right ventricle is complex, requiring multimodality imaging to include specialised echocardiography and cross-sectional imaging (MRI and CT). In the current era, most neonates undergo the arterial switch operation with increasing understanding of near-term and long-term outcomes specific to their cardiac anatomy. Long-term observations of the Lecompte manoeuvre or coronary stenoses following transfer continue, with evolving understanding to improve surveillance. Ultimately, an understanding of postsurgical anatomy, specialised imaging techniques and interventional and electrophysiological procedures is essential to comprehensive care of D-TGA survivors.

Role of virtual reality in congenital heart disease.

OBJECTIVE: New platforms for patient imaging present opportunities for improved surgical planning in complex congenital heart disease (CHD). Virtual reality (VR) allows for interactive manipulation of high-resolution representations of patient-specific imaging data, as a supplement to traditional 2D visualizations and 3D printed heart models. DESIGN: We present the novel use of VR for the presurgical planning of cardiac surgery in two infants with complex CHD to demonstrate interactive real-time views of complex intra and extracardiac anatomy. RESULTS: The use of VR for cardiac presurgical planning is feasible using existing imaging data. The software was evaluated by both pediatric cardiac surgeons and pediatric cardiologists, and felt to be reliable and operated with a very short learning curve. CONCLUSIONS: VR with controller-based interactive capability allows for interactive viewing of 3D models with complex intra and extracardiac anatomy. This serves as a useful complement to traditional preoperative planning methods in terms of its potential for group based collaborative discussion, user defined illustrative views, cost-effectiveness, and facility of use.

Cardiac strain findings in children with latent rheumatic heart disease detected by echocardiographic screening.

BACKGROUND: Identification of patients with latent rheumatic heart disease by echocardiography presents a unique opportunity to prevent disease progression. Myocardial strain is a more sensitive indicator of cardiac performance than traditional measures of systolic function. OBJECTIVE: The objective of this study was to test the hypothesis that abnormalities in myocardial strain may be present in children with latent rheumatic heart disease. METHODS: Standard echocardiography images with electrocardiogram gating were obtained from Ugandan children found to have latent rheumatic heart disease as well as control subjects. Traditional echocardiography measures of systolic function were obtained, and offline global longitudinal strain analysis was performed. Comparison between groups was performed using strain as a continuous (Mann-Whitney U-test) and categorical (cut-off 5th percentile for age) variable. RESULTS: Our study included 14 subjects with definite rheumatic heart disease, 13 with borderline rheumatic heart disease, and 112 control subjects. None of the subjects had abnormal left ventricular size or ejection fraction. Global longitudinal strain was lower than the 5th percentile in 44% of the subjects with any rheumatic heart disease (p=0.002 versus controls) and 57% of the subjects with definite rheumatic heart disease (p=0.03). The mean absolute strain values were significantly lower when comparing subjects with any rheumatic heart disease with controls (20.4±3.95 versus 22.4±4.35, p=0.025) and subjects with definite rheumatic heart disease with controls (19.9±4.25 versus 22.4±4.35, p=0.033). CONCLUSION: Global longitudinal strain is decreased in subjects with rheumatic heart disease in the absence of abnormal systolic function. Larger studies with longer-term follow-up are required to determine whether there is a role for strain to help better understand the pathophysiology of latent rheumatic heart disease.

Utility of fetal magnetic resonance imaging in assessing the fetus with cardiac malposition.

OBJECTIVE: Abnormal cardiac axis and/or malposition prompts evaluation of congenital heart disease; however, etiology may be difficult to clarify using obstetrical ultrasound or fetal echocardiography (echo) alone. We aimed to use fetal magnetic resonance imaging (MRI) as a complementary tool to identify causes of cardiac malposition. METHODS: Review of fetuses diagnosed with cardiac malposition by fetal ultrasound and echo was performed. Etiology was classified as either because of heterotaxy syndrome or extracardiac masses. Reclassification was then performed with fetal MRI findings. Results were compared with postnatal diagnoses. RESULTS: Forty-two fetuses were identified as having abnormal cardiac axis and/or malposition. Twenty three of 42 cases (55%) had extracardiac anomalies, while 19 (45%) were because of heterotaxy. Twelve of 42 (29%) cases were reassigned by fetal MRI (five in heterotaxy group and seven in the lung anomaly group). Four cases (33%) had both cardiac disease and extracardiac masses, not previously recognized. Fetal MRI clarified heterotaxy subtype or removed heterotaxy diagnosis in five (26%) patients. Fetal MRI findings were confirmed in 8 of these 12 cases postnatally. CONCLUSION: Fetal MRI is a useful complementary tool to define etiology of cardiac malposition in complex cases for informative prenatal counseling and planning. © 2016 John Wiley & Sons, Ltd.

Upper arm and cardiac magnetic resonance imaging in Duchenne muscular dystrophy.

We analyzed quantitative maps of T1 and T2 relaxation times and muscle fat fraction measurements in magnetic resonance imaging of the upper arm skeletal muscles and heart in ambulatory boys with Duchenne muscular dystrophy and age-range-matched healthy volunteer boys. The cardiac-optimized sequences detected fatty infiltration and edema in the upper arm skeletal muscles but not the myocardium in these Duchenne muscular dystrophy boys who had normal ejection fraction. Imaging the heart and skeletal muscle using the same magnetic resonance imaging methods during a single scan may be useful in assessing relative disease status and therapeutic response in clinical trials of Duchenne muscular dystrophy.

The utility of handheld echocardiography for early rheumatic heart disease diagnosis: a field study.

AIMS: The World Heart Federation (WHF) guidelines for rheumatic heart disease (RHD) are designed for a standard portable echocardiography (STAND) machine. A recent study in a tertiary care centre demonstrated that they also had good sensitivity and specificity when modified for use with handheld echocardiography (HAND). Our study aimed to evaluate the performance of HAND for early RHD diagnosis in the setting of a large-scale field screening. METHODS AND RESULTS: STAND was performed in 4773 children in Gulu, Uganda, with 10% randomly assigned to also undergo HAND. Additionally, any child with mitral or aortic regurgitation also underwent HAND. Studies were performed by experienced echocardiographers and blindly reviewed by cardiologists using 2012 WHF criteria, which were modified slightly for HAND--due to the lack of spectral Doppler capability. Paired echocardiograms were performed in 1420 children (mean age 10.8 and 53% female), resulting in 1234 children who were normal, 133 who met criteria for borderline RHD, 47 who met criteria for definite RHD, and 6 who had other diagnoses. HAND had good sensitivity and specificity for RHD detection (78.9 and 87.2%, respectively), but was most sensitive for definite RHD (97.9%). Inter- and intra-reviewer agreement ranged between 66-83 and 71.4-94.1%, respectively. CONCLUSIONS: HAND has good sensitivity and specificity for diagnosis of early RHD, performing best for definite RHD. Protocols for RHD detection utilizing HAND will need to include confirmation by STAND to avoid over-diagnosis. Strategies that evaluate simplified screening protocols and training of non-physicians hold promise for more wide spread deployment of HAND-based protocols.

Noncoronary inflammation in Kawasaki disease is associated with abnormal myocardial deformation in the acute phase.

BACKGROUND: Patients with Kawasaki disease (KD) are at risk for developing coronary artery lesions, but the association of noncoronary changes such as mitral regurgitation (MR) and/or pericardial effusion (PE) with cardiac mechanics in the acute phase of KD has not been previously described. The aim of this study was to test the hypothesis that these noncoronary markers for carditis are associated with abnormalities in strain (ε) and strain rate (SR) in patients with MR or PE not appreciated by conventional echocardiography. METHODS: Longitudinal and circumferential ε and SR analyses were retrospectively performed on patients with KD. Patients with and without MR or PE were compared. Strain values were also compared between patients with and without coronary artery lesions. Values for ejection fraction, shortening fraction, and clinical laboratory parameters were correlated with MR or PE. Follow-up echocardiographic outcomes were recorded at the first encounter after initial diagnosis. Follow-up ε and SR data were also obtained in the group with MR or PE and altered ventricular mechanics at diagnosis. RESULTS: Of the 110 patients reviewed, 92 had appropriate image quality for either longitudinal ε and SR or circumferential ε and SR analysis. Twenty-eight patients (30%) had either MR or PE. Longitudinal ε and SR were significantly decreased in patients with MR or PE compared with patients without MR or PE (ε: -16.4 ± 4.0% vs -19.0 ± 3.7%, P = .004; SR: -1.3 ± 0.7 vs -1.6 ± 0.4 sec(-1), P = .03). No significant difference in longitudinal ε or SR was noted between patients with and without coronary artery lesions (ε: -17.9 ± 4.1% vs -17.8 ± 3.8%, P = .50; SR: -1.5 ± 0.3 vs -1.6 ± 0.8 sec(-1), P = .50). In the group with abnormal coronary arteries, presence of MR or PE was correlated with decreased longitudinal ε (-16.1 ± 3.6% vs -18.9 ± 3.4%, P = .02), without a significant difference in longitudinal SR (-1.6 ± 0.4 vs -1.5 ± 0.4 sec(-1), P = .20). At approximately 3-week follow-up (21.3 ± 15.8 days), longitudinal ε and SR for the group with MR or PE had increased significantly compared with diagnosis (ε: -16.4 ± 4.3% vs -18.6 ± 0.5%, P = .03; SR: -1.3 ± 0.6 vs -1.8 ± 0.4 sec(-1), P = .008), coincident with resolution of MR or PE. In both groups, erythrocyte sedimentation rate and C-reactive protein were elevated (85.3 ± 36.2 mm/h vs 75.1 ± 33.1 mm/h [P = .34] and 12.3 ± 6.7 vs 11.7 ± 8.2 mg/dL [P = .83]), but only modest correlations were noted between longitudinal ε and elevated erythrocyte sedimentation rate (r = 0.52, P = .01; confidence interval, 0.10-0.80) and C-reactive protein (r = 0.50, P = .02; confidence interval, 0.10-0.80) in patients with MR or PE. Shortening fraction and ejection fraction were within the normal range in both groups. CONCLUSIONS: Patients presenting with KD with MR or PE at diagnosis are likely to have altered ventricular mechanics compared with patients with KD without MR or PE despite normal conventional echocardiographic measures of function. There is no significant difference in ventricular mechanics when comparing patients with KD with coronary ectasia or aneurysms and those without coronary lesions. Presence of abnormal ε in patients with KD with altered ventricular mechanics correlates modestly with laboratory inflammatory markers. Peak systolic longitudinal ε and SR increased significantly at 3-week follow-up compared with initial diagnosis, coincident with resolution of MR or PE.

Tricuspid atresia with aortopulmonary window: challenges in achieving a balanced circulation.

Tricuspid atresia and aortopulmonary window are rare congenital cardiac anomalies. The occurrence of both these anomalies in the same patient is extremely rare, with only 1 case reported in the literature. We report the surgical management of one such patient and discuss the management issues with respect to Stage 1 single ventricle palliation.

Prenatal transplantation of cytokine-stimulated marrow improves early chimerism in a resistant strain combination but results in poor long-term engraftment.

OBJECTIVE: In the absence of immunodeficiency, only microchimerism (<0.1%) has been achieved in human fetal recipients or nonhuman primates following in utero hematopoietic cell transplantation (IUHCT). We hypothesized that enhanced long-term engraftment might be more reliably achieved in microchimeric systems if higher levels of chimerism existed during development of adaptive immunity. To evaluate this hypothesis, we stimulated the donor cells with vascular endothelial growth factor (VEGF) and stem cell factor (SCF) prior to IUHCT in a chimerism-resistant murine strain combination. METHODS: Donor Balb/c marrow was cultured in media with or without VEGF and SCF supplementation for 12 hours prior to IUHCT into B6 fetuses at 14 days postcoitum (dpc). Donor cell phenotype, homing, and chimerism were assessed at short and long-term time points and transplanted animals received skin allografts at 8 weeks. RESULTS: In pretreated allogeneic recipients, early chimerism rates were more than double that of controls (71% vs 33%, p = 0.01). These differences were associated with higher numbers of pretransplant donor cell colony-forming cells without change in donor cell homing. Despite prolonged skin allograft survival for pretreated recipients compared with controls (mean survival = 20.8 vs 8.2 days, p < 0.001), long-term engraftment was unchanged. CONCLUSIONS: These findings demonstrate that higher levels of early chimerism in recipients of cytokine-stimulated marrow result in improved short-term chimerism and tolerance. Future studies are needed to confirm the existence of a "threshold" level of chimerism necessary to sustain long-term engraftment.