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Background Coronary cardiovascular magnetic resonance angiography (CCMRA) of congenital heart disease (CHD) in pediatric patients requires accurate planning, adequate sequence parameter adjustments, lengthy scanning sessions, and significant involvement from highly trained personnel. Anesthesia and intubation are commonplace to minimize movements and control respiration in younger subjects. To address the above concerns and provide a single-click imaging solution, we applied our free-running framework for fully self-gated (SG) free-breathing 5D whole-heart CCMRA to CHD patients after ferumoxytol injection. We tested the hypothesis that spatial and motion resolution suffice to visualize coronary artery ostia in a cohort of CHD subjects, both for intubated and free-breathing acquisitions. Methods In 18 pediatric CHD patients, non-electrocardiogram (ECG) triggered 5D free-running gradient echo CCMRA with whole-heart 1 mm3 isotropic spatial resolution was performed in seven minutes on a 1.5T CMR scanner. Eleven patients were anesthetized and intubated, while seven were breathing freely without anesthesia. All patients were slowly injected with ferumoxytol (4 mg/kg) over 15 minutes. Cardiac and respiratory motion-resolved 5D images were reconstructed with a fully SG approach. To evaluate the performance of motion resolution, visibility of coronary artery origins was assessed. Intubated and free-breathing patient sub-groups were compared for image quality using coronary artery length and conspicuity as well as lung-liver interface sharpness. Results Data collection using the free-running framework was successful in all patients in less than 8 min; scan planning was very simple without the need for parameter adjustments, while no ECG lead placement and triggering was required. From the resulting SG 5D motion-resolved reconstructed images, coronary artery origins could be retrospectively extracted in 90% of the cases. These general findings applied to both intubated and free-breathing pediatric patients (no difference in terms of lung-liver interface sharpness), while image quality and coronary conspicuity between both cohorts was very similar. Conclusions A simple-to-use push-button framework for 5D whole-heart CCMRA was successfully employed in pediatric CHD patients with ferumoxytol injection. This approach, working without any external gating and for a wide range of heart rates and body sizes provided excellent definition of cardiac anatomy for both intubated and free-breathing patients.

Background Surgical and catheter-based interventions for congenital heart disease require precise understanding of complex anatomy. The use of three-dimensional (3D) printing and virtual reality to enhance visuospatial understanding has been well documented, but integration of these methods into routine clinical practice has not been well described. We review the growth and development of a clinical 3D modeling service to inform procedural planning within a high-volume pediatric heart center. Methods Clinical 3D modeling was performed using cardiac magnetic resonance (CMR) or computed tomography (CT) derived data. Image segmentation and post-processing was performed using FDA-approved software. Patient-specific anatomy was visualized using 3D printed models, digital flat screen models and virtual reality. Surgical repair options were digitally designed using proprietary and open-source computer aided design (CAD) based modeling tools. Results From 2018 to 2020 there were 112 individual 3D modeling cases performed, 16 for educational purposes and 96 clinically utilized for procedural planning. Over the 3-year period, demand for clinical modeling tripled and in 2020, 3D modeling was requested in more than one-quarter of STAT category 3, 4 and 5 cases. The most common indications for modeling were complex biventricular repair (n = 30, 31%) and repair of multiple ventricular septal defects (VSD) (n = 11, 12%). Conclusions Using a multidisciplinary approach, clinical application of 3D modeling can be seamlessly integrated into pre-procedural care for patients with congenital heart disease. Rapid expansion and increased demand for utilization of these tools within a high-volume center demonstrate the high value conferred on these techniques by surgeons and interventionalists alike.

The purpose of this study was to assess the safety and indications for cardiac magnetic resonance (CMR) with myocardial perfusion imaging (MPI) in a cohort of children and young adults. A retrospective review of 178 children and young adults who underwent CMR with MPI was performed. Studies were categorized based on study protocols as MPI with resting perfusion only, adenosine stress MPI, exercise-induced stress MPI, and MPI for cardiac mass diagnosis. Relevant clinical history, exam indications, and adverse reactions following gadolinium-based contrast agent and adenosine administration were recorded. Studies were reviewed for the presence of myocardial perfusion defects, wall motion abnormalities, and delayed myocardial enhancement. The most common indications from MPI were congenital heart disease (CHD), Kawasaki disease, anomalous coronary artery, or myocardial mass characterization. Of these, 51% were protocoled with adenosine stress, 23% without stress, 6% with exercise stress, and 20% for cardiac mass evaluation. Excluding patients for myocardial mass evaluation, MPI defects were present in 16% (14 with adenosine stress, 1 with exercise stress, 8 on resting studies only). For cardiac mass evaluation, a mass was confirmed in 58%. No adverse reactions occurred with intravenous administration of a gadolinium-based contrast agent. Three self-limited adverse reactions, 2 patients with chest pain, and 1 patient with bradycardia, occurred following adenosine administration. MPI is a safe modality for the evaluation of pediatric and young adults with minimal adverse events. The most common indications for MPI were for the evaluation of CHD, Kawasaki disease, anomalous coronary artery, or myocardial mass characterization.

A non-contractile transannular patch (TAP) in the right ventricular outflow tract (RVOT) contributes to ventricular dysfunction after tetralogy of Fallot (TOF) repair. We compared regional right ventricular (RV) strain in repaired TOF with valvar pulmonary stenosis (VPS) after balloon valvuloplasty to investigate the effects of TAP. Retrospective review of 26 cardiac magnetic resonance studies of TOF (n = 13) and VPS (n = 13) subjects matched by degree and duration of pulmonary regurgitation (PR). Feature tracking strain analysis was performed. Student's t tests, Pearson correlation, and linear regression were applied. RV ejection fraction (EF) was normal and similar between TOF and VPS (60 and 65%, respectively, p = 0.8). RV 4-chamber Lagrangian longitudinal strain (RV 4ch LS) was worse in both groups compared to normals but comparable to each other: -18.2 (95% CI -3.6 to -33) for TOF and -20.2 (95% CI -12.4 to -28) for VPS, p = 0.5. RVOT LS was worse than RV 4ch LS in TOF, p = 0.05, but not in VPS, p = 0.19. There were no significant differences in RVOT strain between groups, p = 0.18. RVOT strain and RV 4ch LS correlated positively with RV EF in VPS (r = 0.72, p = 0.003 and r = 0.55, p = 0.04). PR degree correlated negatively with RVOT LS for TOF and VPS. Longitudinal strain is diminished in VPS and TOF subjects with preserved RV EF. TAP could explain worse RVOT strain in TOF. Longitudinal studies are needed to ascertain if RV strain predicts worsening of RV EF.

Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause strokes and seizures in younger individuals. CCMs arise from endothelial cell loss of KRIT1, CCM2 or PDCD10, non-homologous proteins that form an adaptor complex. How disruption of the CCM complex results in disease remains controversial, with numerous signalling pathways (including Rho, SMAD and Wnt/β-catenin) and processes such as endothelial-mesenchymal transition (EndMT) proposed to have causal roles. CCM2 binds to MEKK3 (refs 7, 8, 9, 10, 11), and we have recently shown that CCM complex regulation of MEKK3 is essential during vertebrate heart development. Here we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we show that expression of the MEKK3 target genes Klf2 and Klf4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. By contrast, we find no evidence of EndMT or increased SMAD or Wnt signalling during early CCM formation. Endothelial-specific loss of Map3k3 (also known as Mekk3), Klf2 or Klf4 markedly prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we show that endothelial expression of KLF2 and KLF4 is increased in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates the MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signalling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.

There is an established association between tetralogy of Fallot and partial anomalous pulmonary venous connections. This association is important because surgically repaired tetralogy patients have increased risk of right heart failure. We hypothesize that partial anomalous venous connections increase right ventricular volumes and worsen right ventricular failure.We reviewed cardiac MRI exams performed at a tertiary pediatric hospital from January 2005 to January 2014. We identified patients with repaired tetralogy and unrepaired partial anomalous pulmonary venous connection. We used age- and gender-matched repaired tetralogy patients without partial anomalous pulmonary venous connection as controls. We analyzed the MRI results and surgical course and performed comparative statistics to identify group differences.There were eight patients with repaired tetralogy and unrepaired partial anomalous pulmonary venous connection and 16 controls. In all cases, the partial anomalous pulmonary venous connection was not detected on preoperative echocardiography. There were no significant differences in surgical course and body surface area between the two groups. Repaired tetralogy patients with unrepaired partial anomalous pulmonary venous connection showed significantly higher indexed right ventricular end diastolic volume (149 ± 33 mL/m(2) vs. 118 ± 30 mL/m(2)), right ventricle to left ventricle size ratios (3.1 ± 1.3 vs. 1.9 ± 0.5) and a higher incidence of reduced right ventricular ejection fraction compared to controls (3/8 vs. 0/16).Repaired tetralogy of Fallot with unrepaired partial anomalous pulmonary venous connection is associated with reduced right ventricular ejection fraction and more significant right ventricular dilation.

Tricuspid annular plane systolic excursion (TAPSE) reflects longitudinal myocardial shortening, the main component of right ventricular (RV) contraction in normal hearts. To date, TAPSE has not been extensively studied in patients with hypoplastic left heart syndrome (HLHS) and systemic RVs after Fontan palliation. This retrospective study investigated HLHS patients after Fontan with cardiac magnetic resonance (CMR) performed between 1 January 2010 and 1 August 2012 and transthoracic echocardiogram (TTE) performed within 6 months of CMR. The maximal apical displacement of the lateral tricuspid valve annulus was measured on CMR (using four-chamber cine images) and on TTE (using two-dimensional apical views). To create TTE-TAPSE z-scores, published reference data were used. Intra- and interobserver variability was tested with analysis of variance. Inter-technique agreement of TTE and CMR was tested with Bland-Altman analysis. In this study, 30 CMRs and TTEs from 29 patients were analyzed. The age at CMR was 14.1 ± 7.1 years, performed 11.9 ± 7.8 years after Fontan. For CMR-TAPSE, the intraclass correlation coefficients for inter- and intraobserver variability were 0.89 and 0.91, respectively. The TAPSE measurements were 0.57 ± 0.2 cm on CMR and 0.70 ± 0.2 cm on TTE (TTE-TAPSE z score, -8.7 ± 1.0). The mean difference in TAPSE between CMR and TTE was -0.13 cm [95 % confidence interval (CI) -0.21 to -0.05], with 95 % limits of agreement (-0.55 to 0.29 cm). The study showed no association between CMR-TAPSE and RVEF (R = 0.08; p = 0.67). In patients with HLHS after Fontan, TAPSE is reproducible on CMR and TTE, with good agreement between the two imaging methods. Diminished TAPSE suggests impaired longitudinal shortening in the systemic RV. However, TAPSE is not a surrogate for RVEF in this study population.

Background Assessing aortic valve stenosis (AVS) by cardiac magnetic resonance (CMR) remains challenging, largely due to effects of accelerated flow and resulting pressure recovery, or the phenomena of kinetic energy transmuting to static fluid pressure distally. Effective orifice area (EOA) is a technique used in echocardiography and has been shown to improve AVS assessment. The potential of phasecontrast velocity mapping (PC-MRI) to improve the accuracy of EOA rests on the ability to resolve high peak velocities; previous studies have shown systematic underestimation compared to echocardiography. We used in vitro experiments to assess the accuracy of EOA using the continuity equation with PC-MRI derived peak velocities and flows.

This study examined the correlation of echocardiography (ECHO) and Cardiac Magnetic Resonance (CMR) in the assessment of aortic valve regurgitation (AR) in children and young adults with congenital heart disease. We hypothesized that qualitative ECHO assessment correlates insufficiently with quantitative CMR data and compared subjective ECHO evaluations with objective measurement of regurgitant fractions (RF) by CMR. Patients who had both ECHO and CMR assessments of AR within 60 days of each other were included. The qualitative ECHO assessment (mild, moderate, severe) of AR and left ventricular dimension at end diastole were recorded. RF was quantified by CMR using phase-contrast velocity mapping. Repeat ECHO review and grading of AR was performed by a blinded single reader in a randomly chosen subgroup of patients. In 43 patients studied, statistical significance was observed in the CMR-RF between mild and moderate, and between mild and severe ECHO grades. There was significant overlap of objective RF between subjective grades. Mild ECHO AR corresponded to an RF (%) of 0-29, moderate 1-40, and severe 5-58. Overlap was more significant at moderate and severe grades. Results were similar in the group in whom a single reader interpreted the ECHO assessment. In conclusion, results derived from a real-life multiple-reader ECHO laboratory showed inconsistencies in ECHO grading of AR, with a wide range of objectively measured RF within a given ECHO grade. ECHO is less reliable in identifying more severe AR, often overestimating severity. Quantitative CMR is a potentially useful supplement to ECHO for management decisions and assessments of medical and surgical therapies in children and young adults with AR.

Background Feature-tracking Strain (FT S) is a new technique that performs myocardial Strain evaluation on Steady State Free Precession (SSFP) cines without the need for myocardial tagging. As a pilot study to determine whether FT S may be useful in single ventricle patients, we applied this analysis to patients with hypoplastic left heart syndrome (HLHS) and tricuspid atresia (TA). Methods We retrospectively reviewed 22 patients with a history of Fontan palliation (median age 8.2, range 2 - 27.5 years) who had cardiac MRIs with a Siemens 1.5 Tesla Avanto (Siemens Medical Systems) scanner, 11 with TA, 11 with HLHS. All had steady-state free precession (SSFP) sequences of 4-chamber (4ch) cine and short axis (SAx) cine stacks from cardiac base to apex. Ejection fraction (EF) was calculated from the SAx stack on a Leonardo workstation (Siemens, Inc.). FT S analysis of the 4ch cine was performed off-line with TomTec 2D Cardiac Performance Analysis (version 1.0, TomTec Imaging Systems) following two tracking protocols: endocardial trace only (Endo), epicardial to endocardial trace (Endo-Epi) (Figure 1). Pearson correlation was used to test relationship between absolute global longitudinal Strain (GLSabs) and EF. Differences in GLS between tracking methods were tested with Bland Altman analysis. Results Mean EF was 60.2%, 95% CI 42.6% to 77.8%. Mean GLS was -15.7 (95% CI -6.8 to -24.7) by Endo., and -16.5 (95% CI -6.9 to -26.1) by Endo-Epi tracking methods. There was fair correlation (Figure 2) between GLSabs and EF using the Endo method (Pearson r = 0.67, p mean Endo GLS of 0.8, with a wide distribution in difference values, 95% CI 2.9 to -4.5. Morphologic ventricle type (single LV vs single RV) did not make a difference in GLS to EF correlations when compared to the mixed cohort. Mean GLS for single LVs was somewhat higher than single RVs, but this difference did not reach statistical significance. Conclusions There is fair correlation between GLS and EF in single ventricle patients with feature-tracking Strain analysis tracking the ventricular endocardium. Validation in a larger sample is warranted. Comparison of FT S with tagged harmonic phase MRI in single ventricle patients may further validate this promising technique in defining regional and global strain. Funding

Repaired conotruncal anomaly pts may have residual branch pulmonary artery (BPA) stenosis or significant differences in the sizes of the BPAs. Phase-Contrast Magnetic Resonance (PCMR) can measure differential BPA regurgitation.

Corrigendum: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases

It is generally assumed that blood behaves strictly as a particle-free fluid and not as a suspension in arterial sized vessels (> 1 mm). However, we have previously demonstrated a biphasic deviation of pressure gradients(PG) of blood from a particle-free fluid of equal viscosity in straight tubes, with the blood PG being greater than the particle-free fluid at low flowrates and lower at high flowrates. Since this behavior may affect velocity-derived PG, we addressed the hypothesis that PG across a BT shunt would show significant deviation from that of a particle-free blood analog fluid (BAF). Methods: The in vitro BT shunt model consisted of two arterial sections connected by a physiologically sized shunt (D = 5 mm, L = 9 cm). PG across the shunt were obtained by measuring pressure 10 cm proximal and distal to the inlet and outlet respectively. For a given flow rate the PG across the shunt was recorded for both blood and an equal viscosity BAF(aqueous glycerin solution, 3.8 cP). PG differences were plotted vs. Reynolds number (Re = ratio of inertial to viscous forces) and divided into laminar and turbulent flow regimes, with a transition Re of 2100 (the approximate transition from laminar to turbulent flow in tubes). Differences in PG between blood and BAF were considered significant at a level of 0.01 using a paired t-test for both the laminar and turbulent regimes. Results: For Re 0.5). However, for Re > 2100, the PG for blood were consistently lower than that of BAF and the differences were significant (mean difference = 9.9 mmHg, p < 0.01). Conclusions: Blood PG across BT shunts deviate from BAF PG. This effect is especially pronounced in the turbulent regime and is consistent with our previous investigations using straight tubes, suggesting Re-dependent phenomena may account for this behavior. These findings may have important implications in the noninvasive assessment of pulmonary artery pressure in patients with BT shunts.

VESSEL COMPLIANCE MISMATCH CAN INCREASE WORKLOAD OF THE LEFT VENTRICLE IN ABSENCE OF OBSTRUCTION AFTER REPAIR OF AORTIC COARCTATION. † 220