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Voltage dependent anion channel 2 (VDAC2) is an outer mitochondrial membrane porin known to play a significant role in apoptosis and calcium signaling. Abnormalities in calcium homeostasis often leads to electrical and contractile dysfunction and can cause dilated cardiomyopathy and heart failure. However, the specific role of VDAC2 in intracellular calcium dynamics and cardiac function is not well understood. To elucidate the role of VDAC2 in calcium homeostasis, we generated a cardiac ventricular myocyte-specific developmental deletion of Vdac2 in mice. Our results indicate that loss of VDAC2 in the myocardium causes severe impairment in excitation-contraction coupling by altering both intracellular and mitochondrial calcium signaling. We also observed adverse cardiac remodeling which progressed to severe cardiomyopathy and death. Reintroduction of VDAC2 in 6-week-old knock-out mice partially rescued the cardiomyopathy phenotype. Activation of VDAC2 by efsevin increased cardiac contractile force in a mouse model of pressure-overload induced heart failure. In conclusion, our findings demonstrate that VDAC2 plays a crucial role in cardiac function by influencing cellular calcium signaling. Through this unique role in cellular calcium dynamics and excitation-contraction coupling VDAC2 emerges as a plausible therapeutic target for heart failure., The authors found that VDAC2 plays a crucial role in influencing mitochondrial calcium dynamics and cellular calcium signalling. A VDAC2 agonist, efsevin, rescued the heart failure phenotype, identifying a new potential therapeutic target for heart failure.

Background Patients with single ventricle (SV) may often undergo aortic reconstruction that creates a stiff large vessel, increasing afterload and affecting exercise performance. The objective of this study was to determine the relationship of pulse wave velocity (PWV) and distensibility in reconstructed and normal aortic arches after Fontan with exercise variables. Methods PWV and distensibility of the descending aorta at the level of the diaphragm (DAo) were calculated with real-time exercise cardiac magnetic resonance in 48 patients with SV after Fontan (18 after aortic reconstruction; 30 without aortic reconstruction) and compared with metabolic exercise stress test variables. Results PWV was greater in the reconstructed group than in the non-reconstructed group (median 4.4 m/s [range: 2.3 to 9.8 m/s] versus 3.6 [range: 2.6 to 6.3 m/s], respectively, p = 0.003). Statistically significant inverse correlations were found between PWV and end-diastolic, end-systolic, and stroke volumes at rest and at exercise in the reconstructed group. In addition, inverse correlations also existed in the reconstructed group between distensibility of the DAo and the exercise variables such as peak oxygen pulse (R = 0.56, p = 0.02), peak oxygen consumption (R = 0.63, p = 0.008), oxygen consumption at ventilatory anaerobic threshold (R = 0.48, p = 0.04), and peak work (R = 0.54, p = 0.02). Similar correlations were not seen in patients with non-reconstructed aortas. Conclusions Patients with SV with reconstructed aortas have increased aortic stiffness, increasing afterload on the ventricle. Native DAo stiffness distal to the reconstruction is inversely correlated with exercise performance, presumably to decrease impedance mismatch to maintain homogeneity of the aortic wall. This information suggests a possible mechanism for decreased exercise performance in patients with SV with aortic reconstructions.

Background As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease. Objective We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease. Study Design This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks’ gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis. Results Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25–2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10–2.36). Conclusion Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.

Introduction: Three-dimensional echocardiography (3DE) has been shown to be superior to 2DE when quantifying chamber dimensions. However, the clinical utility of 3DE has been limited by time-consuming analysis and need for 3D-specific training. This study aims to assess the clinical utility of a “hands-off,” artificial intelligence-driven software program, Philips Dynamic HeartModelA.I. (DHM), in a pediatric population. Hypothesis: We hypothesize that this program will be able to accurately calculate LVEF in children when compared to Cardiac MRI (CMRI) used as a gold standard. Methods: To date, 10 patients (Average Age 14.8±1.9) have undergone CMRI immediately followed by echocardiography at the Children’s Hospital of Philadelphia. Echocardiographic images were analyzed via DHM without manual editing and from full-volume 3D border tracing (3DEF). We excluded 3D imaging of 2 patients due to poor image quality. 2D LVEF was also evaluated visually in all patients by three experts, and by 2D Simpson’s Biplane method. All analyses were timed with a stopwatch. Each technique was correlated with CMRI. Results: Our results showed that LVEF measured via DHM was rapid and correlated very well with CMRI (R=0.85). DHM had a stronger correlation with CMRI than Biplane, 3DEF, and visual EF (R=0.56; R=0.68; R=0.57). Moreover, DHM analysis was faster than both Biplane and 3DEF (32±8 seconds vs 100±19 seconds, p Conclusions: Based on our pilot data, DHM analysis in children was faster than both 3DEF and biplane method likely due to its hands-off nature. Furthermore, its correlation with CMRI was superior to both 3DEF and Biplane. Based on further patient enrollment by us and others, this completely automated method will likely be clinically useful as it has potential to become a standard application in large volume, busy echo labs.

Introduction: Three-dimensional echocardiography (3DE) has been shown to be superior to two-dimensional echocardiography (2DE) for the quantification of chamber volumes and dimensions. However, the utility of 3DE in routine clinical practice has been restricted by time-consuming analysis and the need for 3D-specific training. This study aims to assess the accuracy and clinical utility of Philips Dynamic Heart ModelA.I. (DHM), a “hands off” automated software program, that may be used to measure LA chamber dimensions. This is notable, as indexed LA volume has been used as a predictor of heart failure in adults. Hypothesis: We hypothesize that DHM will be able to quickly and accurately calculate left atrial chamber volume when compared to Cardiac MRI (CMRI) used as a gold standard. Methods: To date, 10 patients (Average Age 14.8±1.9) have undergone clinically indicated CMRI, immediately followed by 3DE, at the Children’s Hospital of Philadelphia. 3D images were analyzed via DHM without manual editing (hands-off approach). DHM automatically calculated maximum LA volume. LA volume was also calculated from CMRI images using the biplane method. LA volume measurements by DHM were correlated with CMRI. Results: DHM was able to calculate LA volume in an average time of 32±8 seconds, without additional human input. Furthermore, inter-technique correlations showed that LA volume measurements made via DHM correlated very well with LA volume measurements made via CMRI (R=0.85, p Conclusions: In children, fully automated evaluation of LA volume based on artificial intelligence is a viable alternative to time-consuming 3D analysis when compared to a CMRI gold standard. This method of “hands-off” analysis may prove to be useful in situations where trained 3D personnel are unavailable. Furthermore, the utilization of this method may result in a greater integration of 3D LA volume into routine clinical practice.

Background Recent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein‐losing enteropathy. However, the role of the lymphatic circulation in early post‐Fontan outcomes is not well defined. Methods and Results This was a retrospective, single‐center study of patients undergoing first‐time Fontan completion from 2012 to 2017. The primary outcome was early Fontan complication ≤6 months after surgery, a composite of death, Fontan takedown, extracorporeal membrane oxygenation, chest tube drainage >14 days, cardiac catheterization, readmission, or transplant. Complication causes were assigned to 1 of 4 groups: (1) Fontan circuit obstruction, (2) ventricular dysfunction or atrioventricular valve regurgitation, (3) persistent pleural effusions in the absence of Fontan obstruction or ventricular dysfunction, and (4) chylothorax or plastic bronchitis. T2‐weighted magnetic resonance imaging sequences were used to assess for lymphatic perfusion abnormality. The cohort consisted of 238 patients. Fifty‐eight (24%) developed early complications: 20 of 58 (34.5%) in group 1, 8 of 58 (14%) in group 2, 18 of 58 (31%) in group 3, and 12 of 58 (20%) in group 4. Preoperative T2 imaging was available for 126 (53%) patients. Patients with high‐grade lymphatic abnormalities had 6 times greater odds of developing early complications ( P =0.001). Conclusions There is substantial morbidity in the early post‐Fontan period. Half of those who developed early complications had lymphatic failure or persistent effusions unrelated to structural or functional abnormalities. Preoperative T2 imaging demonstrated that patients with higher‐grade lymphatic perfusion abnormalities were significantly more likely to develop early complications. This has implications for risk stratification and optimization of patients before Fontan palliation.

Objective We sought to evaluate contractile function in single-ventricle patients before and after imposition of Fontan physiology. Methods Single right ventricle (SRV; n = 38) and single left ventricle (SLV; n = 11) patients underwent cardiac magnetic resonance imaging pre and post Fontan operation. Global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain were measured along with ejection fraction (EF) and atrioventricular valve regurgitation (AVVR). Results Age at cardiac magnetic resonance imaging before the Fontan operation was 3.1 ± 1.3 years and after the Fontan procedure was 5.8 ± 2.7 years. There were no significant EF differences between SRV and SLV patients before and after the Fontan procedure, and EF did not deteriorate significantly after the Fontan operation. GRS was significantly lower for SRV patients than for SLV patients before (24.3% vs 32.1%; P = .048) and after (21.8% vs 29.7%; P = .045) the Fontan procedure. GRS and GCS of the SRV patients deteriorated significantly after the Fontan operation (GRS, P = .01; GCS, P = .009). Strains showed positive correlations before and after the Fontan operation with positive correlations among each strain. Within all patients, strains correlated positively with EF. Strains and EF negatively correlated with AVVR (GRS P = .03, r = −0.22; GCS P = .03, r = −0.23; EF P Conclusions Strains were lower for SRV than for SLV patients before and after the Fontan operation and deteriorated after the Fontan operation. Our study suggests that strain measures might detect ventricular deterioration earlier than EF. Because strains before and after the Fontan operation were positively correlated, and negatively correlated with AVVR, the early institution of myocardial protective therapy including AVVR management, especially for SRV patients, might have benefit.

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.

Objective Exercise intolerance afflicts Fontan patients with total cavopulmonary connections (TCPCs) causing a reduction in quality of life. Optimising TCPC design is hypothesised to have a beneficial effect on exercise capacity. This study investigates relationships between TCPC geometries and exercise haemodynamics and performance. Methods This study included 47 patients who completed metabolic exercise stress test with cardiac magnetic resonance (CMR). Phase-contrast CMR images were acquired immediately following supine lower limb exercise. Both anatomies and exercise vessel flow rates at ventilatory anaerobic threshold (VAT) were extracted. The vascular modelling toolkits were used to analyse TCPC geometries. Computational simulations were performed to quantify TCPC indexed power loss (iPL) at VAT. Results A highly significant inverse correlation was found between the TCPC diameter index, which factors in the narrowing of TCPC vessels, with iPL at VAT (r=−0.723, p 2 ) at VAT (r=0.373, p=0.01), VO 2 at peak exercise (r=0.485, p=0.001) and work at VAT/weight (r=0.368, p=0.01). iPL at VAT was negatively correlated with VO 2 at VAT (r=−0.337, p=0.02), VO 2 at peak exercise (r=−0.394, p=0.007) and work at VAT/weight (r=−0.208, p=0.17). Conclusions Eliminating vessel narrowing in TCPCs and reducing elevated iPL at VAT could enhance exercise tolerance for patients with TCPCs. These findings could help plan surgical or catheter-based strategies to improve patients’ exercise capacity.

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.

Background Little is known of baseline anatomic, hemodynamic, and fluid dynamic cardiac magnetic resonance data in single-ventricle patients immediately after Fontan. A comparison from that time point to the teen years can demonstrate clinical course, potentially predict future events, and may shed some light regarding how to optimize outcome. This cross-sectional study is meant to characterize these variables from just after Fontan to the teenage years. Methods The anatomy, flows, and computational fluid dynamic modeling of 22 patients 3 to 9 months after Fontan (age 3 ± 1.1 years) and 25 teens (age 16 ± 1.8 years) were compared. Significance was defined as P less than .05. Results The percentage of Fontan pathway stenosis was greater with cardiac index and fenestration flow while caval return was lower in teens than in younger patients (for Fontan pathway stenosis, 43% vs 21%, P = .009); however, hepatic flow distribution was more evenly distributed in older patients. Pulmonary artery size kept up with somatic growth. In the teen group, indexed power loss (R = .39), percentage of Fontan pathway stenosis (R = .62), and particle resident time (R = .42) deteriorated as time from Fontan increased (P Conclusions There are mostly aspects of deterioration with a few bright spots of stability in anatomy, blood flow, and fluid dynamic variables in Fontan patients from the postoperative period to the teenage years. Most notably, Fontan pathway stenosis increases with decreasing flows while pulmonary artery size and hepatic flow distribution remain stable or improved. These data may be aid in designing improved Fontan reconstruction to optimize clinical outcome and to understand future complications.

Fontan surgical planning ranks proposed surgical options according to their hemodynamics assessed by computational fluid dynamic (CFD) modeling. CFD commonly utilizes blood flow acquired under breath-holding (BH) conditions. Ignoring the free-breathing (FB) effect on blood flow waveforms may impact the ranking of surgical options. This study investigates such a potential impact by including ten Fontan patients who had blood flow acquisitions under both BH and FB conditions. A virtual surgery platform was used to generate two surgical options for each patient: (1) a traditional Fontan conduit and (2) a Y-graft. These options were ranked based on clinically relevant hemodynamic metrics: power loss (PL) and hepatic flow distribution (HFD). No difference was found in the ranking of options between using FB and BH flow acquisitions. The findings indicated that decision-making is not affected by the types of flow acquisition for Fontan surgical planning.

Surgical optimization of the cavopulmonary connection and pharmacological therapy for dysfunctional Fontan physiology continue to advance, but these treatment approaches only slow the progression of decline to end-stage heart failure. The development of a mechanical cavopulmonary assist device will provide a viable therapeutic option in the bridging of patients to transplant or to stabilization. We hypothesize that rotational blood flow, delivered by an implantable axial flow blood pump, could effectively assist the venous circulation in Fontan patients by mimicking vortical blood flow patterns in the cardiovascular system. This study investigated seven new models of mechanical cavopulmonary assistance (single and dual-pump assist), created combinations of pump designs that deliver counter rotating vortical flow conditions, and analyzed pump performance, velocity streamlines, swirling strength, and energy augmentation in the cavopulmonary circuit for each support scenario. The model having an axial clockwise-oriented impeller in the inferior vena cava and an axial counterclockwise-oriented impeller rotating in the superior vena cava outperformed all of the support scenarios by enhancing the energy of the cavopulmonary circulation an average of 10.3% over the entire flow range and a maximum of 27.4% at %the higher flow rates. This research will guide the development of axial flow blood pumps for Fontan patients and demonstrated the high probability of %a cardiovascular benefit using counter rotating pumps in a dual support scenario, but found that this is dependent upon the patient-specific cavopulmonary anatomy.

Using cardiac magnetic resonance imaging (MRI) with virtual angioscopy, we sought to evaluate coronary anatomy, myocardial injury, and left ventricular function in children with interarterial anomalous aortic origin of coronary artery before and after surgery.We prospectively enrolled children 5 to 19 years old with interarterial anomalous coronary artery. Cardiac MRI was performed with respiratory-navigated steady-state free-precession 3-dimensional data set acquisition. Virtual angioscopy was used to evaluate the coronary ostia directly. Surgery consisted of the modified unroofing procedure.We enrolled 9 subjects between February 2009 and May 2015. Subjects were male, with an average age at surgery of 14.1 years. Anomalous coronary was right in 7 patients (77%) and left in 2. In all subjects, the proximal anomalous coronary arose tangential to the aorta with an elliptical, slitlike ostium. Before the operation, the proximal coronary artery was significantly smaller proximally than distally (2 vs 3.1 mm; P .0001. After the operation, neo-orifices were round and patent in 7 subjects; however, 2 subjects still had narrowed neo-orifices. New postoperative MRI findings included flattened septal wall motion (N = 1), small region of midmyocardial partial-thickness scar (N = 1), and dyskinetic septal wall motion with mild aortic insufficiency (N = 1). Left ventricular function was normal both before and after surgery (P = .85).Cardiac MRI with virtual angioscopy is an important tool for evaluating anomalous coronary anatomy, myocardial function, and ischemia and should be considered for initial and postoperative assessment of children with anomalous coronary arteries.

Background Pulmonary insufficiency is a consequence of transannular patch repair in Tetralogy of Fallot (ToF) leading to late morbidity and mortality. Transcatheter native outflow tract pulmonary valve replacement has become a reality. However, predicting a secure, atraumatic implantation of a catheter-based device remains a significant challenge due to the complex and dynamic nature of the right ventricular outflow tract (RVOT). We sought to quantify the differences in compression and volume for actual implants, and those predicted by pre-implant modeling. Methods We used custom software to interactively place virtual transcatheter pulmonary valves (TPVs) into RVOT models created from pre-implant and post Harmony valve implant CT scans of 5 ovine surgical models of TOF to quantify and visualize device volume and compression. Results Virtual device placement visually mimicked actual device placement and allowed for quantification of device volume and radius. On average, simulated proximal and distal device volumes and compression did not vary statistically throughout the cardiac cycle (P = 0.11) but assessment was limited by small sample size. In comparison to actual implants, there was no significant pairwise difference in the proximal third of the device (P > 0.80), but the simulated distal device volume was significantly underestimated relative to actual device implant volume (P = 0.06). Conclusions This study demonstrates that pre-implant modeling which assumes a rigid vessel wall may not accurately predict the degree of distal RVOT expansion following actual device placement. We suggest the potential for virtual modeling of TPVR to be a useful adjunct to procedural planning, but further development is needed.

Objective Poor total cavopulmonary connection (TCPC) hemodynamics have been hypothesized to be associated with long-term complications in Fontan patients. Image-based Fontan surgical planning has shown great potential as a clinical tool because it can pre-operatively evaluate patient-specific hemodynamics. Current surgical planning paradigms commonly utilize cardiac-gated phase contrast magnetic resonance (MR) imaging to acquire vessel flows. These acquisitions are often taken under breath-held (BH) conditions and ignore the effect of respiration on blood flow waveforms. This study investigates the effect of respiration-driven flow waveforms on patient-specific hemodynamics using real-time MR acquisitions. Methods Patient-specific TCPCs were reconstructed from cardiovascular MR images. Real-time phase contrast MR images were acquired under both free-breathing (FB) and breath-held conditions for 9 patients. Numerical simulations were employed to assess flow structures and hemodynamics used in Fontan surgical planning including hepatic flow distribution (HFD) and indexed power loss (iPL), which were then compared between FB and BH conditions. Results Differences in TCPC flow structures between FB and BH conditions were observed throughout the respiratory cycle. However, the average differences (BH – FB values for each patient, which are then averaged) in iPL and HFD between these conditions were 0.002 ± 0.011 (p = 0.40) and 1 ± 3% (p = 0.28), respectively, indicating no significant difference in clinically important hemodynamic metrics. Conclusions Respiration affects blood flow waveforms and flow structures, but might not significantly influence the values of iPL or HFD. Therefore, breath-held MR acquisition can be adequate for Fontan surgical planning when focusing on iPL and HFD.

Little data are available on the accuracy of phase-contrast magnetic resonance imaging (PC-MRI) velocity mapping in the vicinity of intravascular metal stents other than nitinol stents. Therefore, we sought to determine this accuracy using in vitro experiments. An in vitro flow phantom was used with 3 stent types: (1) 316L stainless steel, (2) nitinol self-expanding, and (3) platinum-iridium. Steady and pulsatile flow was delivered with a magnetic resonance imaging-compatible pump (CardioFlow 5000, Shelley Medical, London, Ontario, Canada). Flows were measured using a transit time flow meter (ME13PXN, Transonic, Inc, Ithaca, New York). Mean flows ranged from 0.5 to 7 L/min. For each condition, 5 PC-MRI acquisitions were made: within the stent, immediately adjacent to both edges of the stent artifact, and 1 cm upstream and downstream of the artifact. Mean PC-MRI flows were calculated by segmenting the tube lumen using clinical software (ARGUS, Siemens, Inc, Erlangen, Germany). PC-MRI and flow meter flows were compared by location and stent type using linear regression, Bland-Altman, and intraclass correlation (ICC). PC-MRI flows within the stent artifact were inaccurate for all stents studied, generally underestimating flow meter-measured flow. Agreement between PC-MRI and flow meter-measured flows was excellent for all stent types, both immediately adjacent to and 1 cm away from the edge of the stent artifact. Agreement was highest for the platinum-iridium stent (R = 0.999, ICC = 0.999) and lowest for the nitinol stent (R = 0.993, ICC = 0.987). In conclusion, PC-MRI flows are highly accurate just upstream and downstream of a variety of clinically used stents, supporting its use to directly measure flows in stented vessels.

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.

Background: Children with single ventricle heart disease are at risk for developing systemic to pulmonary arterial collateral vessels that adversely impact short-term outcomes, although the effect on long-term outcomes remains unclear. Collateral flow (CollF) can be quantified using cardiac magnetic resonance (CMR) flow quantification. The velocity–time integral (VTI), obtained from spectral Doppler tracings, has been used in “runoff” lesions like aortic regurgitation to quantify insufficiency. We hypothesized that the VTI ratio of the proximal descending aorta (DAo) after cavopulmonary anastomosis (CPA) would estimate CollF. Methods: A retrospective cross-sectional study was conducted. Patients who had a superior CPA or total CPA and underwent CMR between April 2008 and December 2012 were included. Those with greater than trivial semilunar valve insufficiency or aortic arch obstruction were excluded. In a subset (n = 88), spectral Doppler tracings of the DAo were analyzed to determine the VTI ratio. In another subset (n = 112), CMR was used to determine the ratio of retrograde to antegrade flow in the DAo. Results: There was no linear correlation between VTI ratio and CollF ( r2 = .006, P = .46). There was a weakly positive correlation with CollF ( r2 = .07, P = .007) and the CMR measured ratio of retrograde to antegrade flow. Holodiastolic flow reversal by echo did not predict higher CollF ( P = .40), but those with holodiastolic flow reversal by CMR had significantly higher CollF ( P = .04). Conclusions: The ratio of reverse to forward flow in the DAo as determined by Doppler echo does not accurately reflect CollF in children with single ventricle after CPA.

Growth hormone and its mediator, insulinlike growth factor 1 (IGF-1), are key determinants of growth in children and young adults. As patients with Fontan physiology often experience diminished longitudinal growth, we sought to describe IGF-1 levels in this population and to identify factors associated with IGF-1 deficiency. Forty-one Fontan subjects ≥5 years were evaluated in this cross-sectional study. Age- and gender-specific height Z scores were generated using national data. Laboratory testing included IGF-1 and brain natriuretic peptide (BNP) levels. IGF-1 levels were converted to age-, gender-, and Tanner stage–specific Z scores. BNP levels were log transformed to achieve a normal distribution (log-BNP). Medical records were reviewed for pertinent clinical variables. Predictors of IGF-1 Z score were assessed through the Student t test and Pearson's correlation. Median age was 11.1 years (range 5.1 to 33.5 years), and time from Fontan was 8.2 years (1.1 to 26.7). Mean height Z score was −0.2 ± 0.9 with a mean IGF-1 Z score of −0.1 ± 1.3. There was no association between IGF-1 Z score and height Z score. Longer interval since Fontan ( R = −0.32, p = 0.04), higher log-BNP ( R = −0.40; p = 0.01), and lower indexed systemic flow on cardiac magnetic resonance ( R = 0.55, p = 0.02) were associated with lower IGF-1 Z scores. In conclusion, in this cohort with Fontan physiology, higher BNP and lower systemic flow were associated with lower IGF-1 Z score. Longitudinal studies are needed to determine if these relations represent a mechanistic explanation for diminished growth in children with this physiology and with other forms of congenital heart disease.

Background As patients with a single-ventricle physiology age, long-term complications inherent to this population become more evident. Previous studies have focused on correlating anatomic and hemodynamic performance, but there is little information of how these variables change with time. Vessel growth and flow rate changes were quantified using cardiac magnetic resonance and their effects on hemodynamics were assessed, which could affect the long-term outcome. Methods Forty-eight patients with a lateral tunnel or extracardiac conduit Fontan who underwent two cardiac magnetic resonance scans (average interval, 5.1 ± 2.3 years) were studied. Total cavopulmonary connection anatomic and flow variables were reconstructed and normalized to body surface area 1/2 . Total cavopulmonary connection hemodynamic efficiency (indexed power loss) was obtained through computational fluid dynamic modeling. Results Absolute vessel diameters increased with time, normalized diameters decreased, and vessel mean flow rates remained unchanged. Indexed power loss changed significantly in the cohort, as well as in patients in whom the minimum normalized left pulmonary artery decreased. Age at first scan and connection type (lateral tunnel or extracardiac conduit) were not associated with changes in indexed power loss. Conclusions We present the largest serial cardiac magnetic resonance Fontan cohort to date. Although flow rates increased proportionally to body surface area, vessel diameters did not match somatic growth. As a result, energy losses increased significantly with time in the cohort analyzed.

Pulse-wave velocity (PWV), a measure of arterial stiffness, is a known independent risk factor for cardiovascular events. Patients with single ventricle who undergo aortic to pulmonary anastomosis (recon) have noncompliant patch material inserted into the neoaorta, possibly increasing vessel stiffness and afterload. The purpose of this study is to determine if PWV in patients with single ventricle differed between those who did and those who did not undergo aortic reconstruction (nonrecon). We retrospectively reviewed cardiac magnetic resonance anatomic, cine, and phase contrast evaluations in the ascending aorta and descending aorta (DAo) at the level of the diaphragm data from 126 patients with single ventricle (8.6 ± 8.0 years) from January 2012 to May 2013. Significance = p0.05. Seventy-five patients underwent recon and 51 did not. PWV in recon was significantly higher than in nonrecon (3.9 ± 0.9 m/s vs 3.2 ± 1.0 m/s, p = 0.008); in recon, patients13 years old had a higher PWV than those7 years (4.5 ± 0.6 vs 3.5 ± 0.7 m/s, p = 0.004). Whether7 or13 years old, PWV of those with recon was higher than nonrecon DAo distensibility was similar between both groups. There was no difference in age, body surface area, or cardiac index between recon and nonrecon. No correlations between various hemodynamic and ventricular function parameters with PWV were noted. In conclusion, PWV in recon is higher than in nonrecon with similar DAo distensibility implicating the aortic reconstruction as a possible cause of increased afterload; older recon patients have stiffer aortas than younger ones, possibly imposing an additional cardiovascular risk in the future. Other biomaterials may potentially moderate PWV if clinical outcome is adversely affected.

A 28-year-old male with Fontan physiology presented with chest pain, elevated troponin, regional dyskinesis, and an apical echogenicity in the right-sided morphologically left ventricle (LV) on echocardiogram. Cardiac magnetic resonance (CMR) imaging was performed with a three-dimensional respiratory-navigated inversion recovery FLASH (low flip angle, spoiled gradient echo technique) sequence during slow gadolinium infusion. A hypointense lesion in the LV apex was consistent with thrombus. Gadolinium-delayed enhancement imaging demonstrated increased signal in the mid-inferior LV free wall. In this case, progressive decline in ventricular function was likely followed by an intracardiac thrombus and embolic myocardial infarction. The CMR was instrumental in characterizing the mass and identifying myocardial scar.

ObjectiveWe previously described lower leg lean mass Z-scores (LLMZ) in Fontan patients associated with worse peak oxygen consumption on metabolic exercise testing. We hypothesised that LLMZ correlates with indexed systemic flow (Qsi) and cardiac index (CI) on exercise cardiac magnetic resonance (eCMR).MethodsThirteen patients had LLM measured by dual-energy X-ray absorptiometry within mean 40 (range 0–258) days of eCMR. LLM was converted to sex and race-specific Z-scores based on healthy reference data. Ventricular volumes and flow measurements of the ascending and descending (DAO) aorta and superior vena cava (SVC) were obtained by CMR at rest and just after supine ergometer exercise to a heart rate associated with anaerobic threshold on prior exercise test. Baseline and peak exercise measures of Qsi (SVC+DAO/BSA) and CI, as well as change in Qsi and CI with exercise, were compared with LLMZ by linear regression.ResultsLLMZ was not correlated with resting flows, stroke volume or CI. There was a strong linear correlation between LLMZ and change in both CI (r=0.77, p=0.002) and Qsi (r=0.73, p=0.005) from rest to exercise. There was also a significant correlation between LLMZ and Qsi at exercise (r=0.70, p=0.008). The correlation between LLMZ and CI at exercise did not reach significance (r=0.3, p=0.07).ConclusionsIn our cohort, there was a strong linear correlation between LLMZ and change in both CI and Qsi from rest to exercise, suggesting that Fontan patients with higher LLMZ may be better able to augment systemic output during exercise, improving performance.

Objectives This study sought to quantify average hemodynamic metrics of the Fontan connection as reference for future investigations, compare connection types (intra-atrial vs extracardiac), and identify functional correlates using computational fluid dynamics in a large patient-specific cohort. Fontan hemodynamics, particularly power losses, are hypothesized to vary considerably among patients with a single ventricle and adversely affect systemic hemodynamics and ventricular function if suboptimal. Methods Fontan connection models were created from cardiac magnetic resonance scans for 100 patients. Phase velocity cardiac magnetic resonance in the aorta, vena cavae, and pulmonary arteries was used to prescribe patient-specific time-averaged flow boundary conditions for computational fluid dynamics with a customized, validated solver. Comparison with 4-dimensional cardiac magnetic resonance velocity data from selected patients was used to provide additional verification of simulations. Indexed Fontan power loss, connection resistance, and hepatic flow distribution were quantified and correlated with systemic patient characteristics. Results Indexed power loss varied by 2 orders of magnitude, whereas, on average, Fontan resistance was 15% to 20% of published values of pulmonary vascular resistance in single ventricles. A significant inverse relationship was observed between indexed power loss and both systemic venous flow and cardiac index. Comparison by connection type showed no differences between intra-atrial and extracardiac connections. Instead, the least efficient connections revealed adverse consequences from localized Fontan pathway stenosis. Conclusions Fontan power loss varies from patient to patient, and elevated levels are correlated with lower systemic flow and cardiac index. Fontan connection type does not influence hemodynamic efficiency, but an undersized or stenosed Fontan pathway or pulmonary arteries can be highly dissipative.

Objective Elevated energy loss in the total cavopulmonary connection (TCPC) is hypothesised to have a detrimental effect on clinical outcomes in single-ventricle physiology, which may be magnified with exercise. This study investigates the relationship between TCPC haemodynamic energy dissipation and exercise performance in single-ventricle patients. Methods Thirty consecutive Fontan patients with TCPC and standard metabolic exercise testing were included. Specific anatomies and flow rates at rest and exercise were obtained from cardiac MR (CMR) and phase-encoded velocity mapping. Exercise CMR images were acquired immediately following supine lower limb exercise using a CMR-compatible cycle ergometer. Computational fluid dynamics simulations were performed to determine power loss of the TCPC anatomies using in vivo anatomies and measured flows. Results A significant negative linear correlation was observed between indexed power loss at exercise and (a) minute oxygen consumption (r=−0.60, p 3.0263 , p Conclusions This is the first study to demonstrate the relationship between power loss and exercise performance with the TCPC being one of the few modifiable factors to allow for improved quality of life. These results suggest that aerobic exercise tolerance in Fontan patients may, in part, be a consequence of TCPC power loss.

We sought to evaluate body composition in children and young adults with Fontan physiology. Leg lean mass (LM) deficits correlate with diminished exercise capacity in other populations and may contribute to exercise limitations in this cohort.This cross-sectional study included whole body dual energy X-ray absorptiometry scans in 50 Fontan participants ≥5 years, and measures of peak oxygen consumption (VO2) in 28. Whole body and leg LM (a measure of skeletal muscle) were converted to sex- and race-specific Z-scores, relative to age and stature, based on 992 healthy reference participants.Median age was 11.5 (range 5.1-33.5) years at 9.3 (1.1-26.7) years from Fontan. Height Z-scores were lower in Fontan compared with reference participants (-0.47±1.08 vs 0.25±0.93, p0.0001). Body mass index Z-scores were similar (0.15±0.98 vs 0.35±1.02, p=0.18). LM Z-scores were lower in Fontan compared with reference participants (whole body LM -0.33±0.77 vs 0.00±0.74, p=0.003; leg LM -0.89±0.91 vs 0.00±0.89, p0.0001). LM Z-scores were not associated with age or Fontan characteristics. Leg LM Z-scores were lower in vitamin D deficient versus sufficient Fontan participants (-1.47±0.63 vs -0.71±0.92, p=0.01). Median per cent predicted peak VO2 was 81% (range 13%-113%) and was associated with leg LM Z-scores (r=0.54, p=0.003).Following Fontan, children and young adults are shorter than their peers and have significant LM deficits. Skeletal muscle deficits were associated with vitamin D deficiency and reduced exercise capacity. Future studies should examine the progression of these deficits to further understand the contribution of peripheral musculature to Fontan exercise capacity.

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.

Holodiastolic flow reversal in the descending aorta on echocardiogram suggests significant aortic regurgitation. The study aim was to determine whether the presence of holodiastolic flow reversal on cardiac magnetic resonance imaging (MRI) correlates with aortic valve regurgitant fraction. We retrospectively reviewed 166 cardiac MRIs (64 % male, age 14.1 ± 9.5 years) from January 2011 to May 2012 where velocity mapping was acquired at both the aortic valve and the descending aorta at the level of the diaphragm. Descending aorta velocity maps were checked for baseline offset using a static reference region. Holodiastolic flow reversal was defined as flow reversal throughout diastole both before and after baseline correction. Significant aortic regurgitation was defined as regurgitant fraction10 %. Aortic valve regurgitant fraction was10 % in 144 patients (Group A), 10-20 % inclusive in 7 patients (Group B), and20 % in 15 patients (Group C). Though the aortic valve regurgitant fraction was significantly higher for patients with holodiastolic flow reversal versus those without (8.5 ± 14.2 vs. 3.8 ± 6.6 %, p = 0.02), holodiastolic flow reversal was present in 32 Group A patients (22 %). In comparison, 4 Group B patients (57 %) and 7 Group C patients (47 %) had holodiastolic flow reversal. The sensitivity (Groups B and C) was 0.5, and the specificity (Group A) was 0.78. Holodiastolic flow reversal in the descending aorta on cardiac MRI was neither sensitive nor specific for predicting significant aortic regurgitation in this study population. Holodiastolic flow reversal in the absence of significant aortic regurgitation may be a relatively common finding in patients with congenital heart disease.

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.

Objectives This study investigated whether cardiac magnetic resonance (CMR) and echocardiography (echo) can replace catheterization (cath) for routine evaluation prior to Fontan and under what circumstances CMR and cath are used together. Background Routine cath prior to Fontan has been utilized for years; noninvasive methods, however, may be sufficient. Methods This study reviews clinical data in 119 consecutive patients investigating 3 groups: those who underwent CMR alone (MR; n = 41), cath alone (C; n = 41), or both cath and CMR (C+M; n = 37) prior to Fontan. Results No clinically significant differences were noted in patient characteristics, hemodynamics, or clinical status prior to or after surgery between the C and MR groups. CMR added information in 82%. There were no discrepant findings between CMR and cath data in the C+M group. Diagnostic success was ≥95% in all groups. Of those undergoing Fontan completion, the C+M group had similar outcomes to C and MR; C and CMR were utilized in combination to assess aortopulmonary collaterals or the need for an intervention or evaluate its success. Echo could not delineate pulmonary arterial anatomy in 46% to 53% of patients. The C+M and C groups were exposed to 6.8 ± 4.1 mSv of radiation. Conclusions Single ventricle patients not requiring an intervention can undergo successful Fontan completion with CMR and echo alone with similar short-term outcomes to C, which was used as a control, preventing an invasive test and exposure to radiation. CMR can add information in a significant number of patients. Cath and CMR are utilized together for interventions and assessment of aortopulmonary collaterals.

Background— Systemic-pulmonary collateral (SPC) flow occurs commonly in single ventricle patients after superior cavo-pulmonary connection, with unclear clinical significance. We sought to evaluate the association between SPC flow and acute post-Fontan clinical outcomes using a novel method of quantifying SPC flow by cardiac magnetic resonance (CMR) imaging. Methods and Results— All patients who had SPC flow quantified by CMR imaging before Fontan were retrospectively reviewed to assess for acute clinical outcomes after Fontan completion. Forty-four subjects were included who had Fontan completion between May 2008 and September 2010. SPC flow prior to Fontan measured 1.5±0.9 L/min/m 2 , accounting for 31±11% of total aortic flow and 44±15% of total pulmonary venous flow. There was a significant linear association between natural log-transformed duration of hospitalization and SPC flow as a proportion of total aortic (rho=0.31, P =0.04) and total pulmonary venous flow (rho=0.29, P =0.05). After adjustment for Fontan type and presence of a fenestration, absolute SPC flow was significantly associated with hospital duration ≥7 days (odds ratio [OR]=9.2, P =0.02) and chest tube duration ≥10 days (OR=22.7, P =0.009). Similar associations exist for SPC flow as a percentage of total aortic (OR=1.09, P =0.048 for hospitalization ≥7 days; OR=1.24, P =0.007 for chest tube duration ≥10 days) and total pulmonary venous flow (OR=1.07, P =0.048 for hospitalization ≥7 days; OR=1.18, P =0.006 for chest tube duration ≥10 days). Conclusions— Increasing SPC flow before Fontan, as measured by CMR imaging, is associated with increased duration of hospitalization and chest tube following Fontan completion.

Left ventricular (LV) diastolic dysfunction is associated with poor outcomes after tetralogy of Fallot (TOF) repair, although its cause is not known, and its relation to right ventricular (RV) performance has never been examined. The aim of this study was to test the hypothesis that RV dilation leads to LV diastolic dysfunction after TOF repair. Patients with repaired TOF who underwent cardiac catheterization and cardiac magnetic resonance imaging within 6 months from January 2003 and April 2011 were reviewed to assess the relation of LV end-diastolic pressure (LVEDP) and indexed RV end-diastolic volume (RVEDVi). Thirty-eight patients were included at a median age of 10.1 years (range 0.6 to 54.7). There was a significant linear association between RVEDVi and LVEDP (p = 0.05). RV end-diastolic pressure (p

Clinicians use branch pulmonary artery (BPA) blood flow distribution to help determine the need for intervention. Although phase-contrast magnetic resonance (PCMR) flow measurements are accurate, this has never been shown in the vicinity of a BPA ferromagnetic stent (FS) which produces significant susceptibility artifact. We retrospectively reviewed 49 consecutive PCMR studies performed from 2005 to 2012 on patients with repaired conotruncal anomalies and either left (n = 29) or right PA (n = 20) stents. Three methods of measuring the stented BPA flow were compared: (1) main PA (MPA) minus nonstented BPA, (2) direct PCMR of stented BPA away from the artifact, and (3) pulmonary venous flows (ipsilateral to stented BPA and derived pulmonary blood flow ratio from bilateral pulmonary venous flows). Internal consistency was tested with the Student t test, linear regression, Bland-Altman analysis, and intraclass correlation (ICC). The mean age was 11.7 ± 6.9 years with 5.8 ± 4.2 years between stent placement and CMR. There was good agreement without significant difference between MPA-derived stented BPA flow (method 1) and direct PCMR of stented BPA (method 2; 41 ± 19% vs 39 ± 19%, p = 0.59; R(2) = 0.84, p0.001; ICC = 0.96). There was also good agreement between methods 1 and 2 compared to pulmonary venous flows, with the highest correlation occurring between method 2 and ipsilateral pulmonary venous flow (R(2) = 0.90, p0.001; ICC = 0.97 for MPA-derived-stented BPA flow; R(2) = 0.94, p0.001; ICC = 0.98 for direct PCMR of stented BPA). Eleven of the 49 patients (22%) underwent interventional catheterization after PCMR. In conclusion, in the vicinity of a BPA FS, accurate measurement of the net fractional pulmonary blood flow ratio is feasible. PCMR adjacent to the stent and ipsilateral pulmonary venous flows provide the most internally consistent data. These data underscore PCMR's utility in managing patients with implanted FS.

The present project investigated whether cardiac magnetic resonance (CMR) of aortic arch anomalies can be performed successfully in infants6 months of age without the use of cardiac anesthesia or deep sedation. We performed a retrospective review of infants ≤6 months old from 2005 to 2009 who underwent either CMR or computed tomography angiography to investigate aortic arch abnormalities. The CMR procedure used a "feed and swaddle" protocol without deep sedation or cardiac anesthesia. Of the 52 infants referred for CMR, 24 underwent the feed and swaddle protocol (aged 2.6 ± 1.4 months). One patient awoke during the study, and examination of the remaining 23 yielded a definitive diagnosis (success rate 96%). The scanning time was 6.2 ± 3.1 minutes, with the large airways evaluation accounting for 1/2 the time. Single-shot axial steady-state free precession, in which the definitive diagnosis was made, accounted for 0.59 ± 0.3 minutes. Fifteen infants were diagnosed with a vascular ring. Of the 8 infants who underwent surgery, the diagnostic accuracy was 100%. During the same period, 19 patients, who had undergone computed tomography angiography (aged 1.67 ± 1.20 months), were referred for aortic arch evaluation. Of these 19 patients, 6 (32%) underwent sedation or anesthesia. The imaging time was 0.08 ± 0.06 minutes, significantly different from the CMR times (p0.01). However, the overall room times (31.3 ± 22.3 and 35.8 ± 3.86 minutes, respectively) were not different between the CMR and angiographic groups. The radiation dose was 1.41 ± 1.03 mSv. In conclusion, CMR evaluation of aortic arch anomalies in children6 months old can be successfully completed quickly using a feed and swaddle approach with high diagnostic accuracy. This protocol avoids the risks of sedation, as well as the radiation associated with computed tomography angiography.

Fontan’s visionary operation and its modifications over the ensuing decades have re-established nonturbulent flow and substantially reduced cyanosis for patients with severe hypoplasia of one ventricle. However, a long list of largely unexpected sequelae has emerged over the last 40 years. Although it is not difficult to understand how care providers could become discouraged, a number of myths have arisen, which we will attempt to dispel with real-world counterexamples as well as with lessons learned from other disciplines: evolutionary, developmental, and computational biology. We argue that distinctive biochemical abnormalities pointing to dysfunction in multiple organs, including the largest organ system in the body, the endothelium, occur long before grossly observable changes in cardiac imaging can be recognized. With a rational redesign of both our surveillance scheme and our wellness strategies, we hope that Fontan survivors and their families, as well as physicians, nurses, and therapists, will see why Fontan’s principle remains just as vibrant today as it was in 1971.

Objective Patients frequently undergo cardiac catheterization before the Fontan operation because of the limited echocardiographic windows in the region of the superior cavopulmonary connection and branch pulmonary arteries. Patients with obstruction to pulmonary blood flow are at increased risk for prolonged length of hospital stay after the Fontan operation. Cardiac magnetic resonance has unlimited imaging windows and can quantify both the branch pulmonary artery size and net flow distribution and thereby serve as a method for identifying patients at increased risk for prolonged length of stay. Methods We retrospectively reviewed 24 cardiac magnetic resonance studies of patients (mean age, 3.1 ± 1.0 years) referred before the Fontan operation. Cardiac magnetic resonance measured the cross-sectional area and flow to each branch pulmonary artery. Post-Fontan hospital course data were acquired from the medical record. Results Prolonged length of stay after the Fontan operation is observed among patients with one branch that is less than 25% of the total cross-sectional area (18.0 ± 5.5 vs 8.2 ± 3.8 days, P = .01) or with less than 40% flow to one branch (12.5 ± 6.9 vs 7.6 ± 1.5 days, P = .04). There is moderate correlation between the total branch pulmonary area and length of stay ( r = −0.75). Conclusions Cardiac magnetic resonance noninvasively assesses the branch pulmonary area size and flow before the Fontan operation. These data predict which patients are more likely to experience a prolonged hospital course.

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.

Objectives Our goal was to determine flow distribution in the cavopulmonary connections of patients with and without bilateral superior venae cavae who had the Fontan procedure. No large series exists that establishes the flow distributions in Fontan patients, which would be an important resource for everyday clinical use and may affect future surgical reconstruction. Methods We studied 105 Fontan patients (aged 2–24 years) with through-plane phase contrast velocity mapping to determine flow rates in the inferior and superior venae cavae and left and right pulmonary arteries. Superior caval anastomosis type included 40 bidirectional Glenn shunts (of which 15 were bilateral) and 53 hemi-Fontan anastomoses; Fontan type included 69 intra-atrial baffles, 28 extracardiac conduits, and 4 atriopulmonary connections. Results Total caval flow was 2.9 ± 1.0 L · min −1 · m −2 , with an inferior vena cava contribution of 59% ± 15%. Total pulmonary flow was 2.5 ± 0.8 L · min −1 · m −2 , statistically less than caval flow and not explained by fenestration presence. The right pulmonary artery contribution (55% ± 13%) was statistically greater than the left. In patients with bilateral superior cavae, the right cava accounted for 52% ± 14% of the flow, with no difference in pulmonary flow splits (50% ± 16% to the right). Age and body surface area correlated with percent inferior caval contribution ( r = 0.60 and 0.74, respectively). Superior vena cava anastomosis and Fontan type did not significantly affect pulmonary flow splits. Conclusions Total Fontan cardiac index was 2.9 L · min −1 · m −2 , with normal pulmonary flow splits (55% to the right lung). Inferior vena caval contribution to total flow increases with body surface area and age, consistent with data from healthy children.

ObjectiveWe quantify the geometric and hemodynamic characteristics of extracardiac and lateral tunnel Fontan surgical options and correlate certain anatomic characteristics with their hemodynamic efficiency and patient cardiac index.Methods and ResultsThe study was conducted retrospectively on 22 patients undergoing Fontan operations (11 extracardiac and 11 lateral tunnel operations). Total cavopulmonary connection geometric parameters such as vessel areas, curvature, and offsets were quantified using a skeletonization method. Energy loss at the total cavopulmonary connection junction was available from previous in vitro experiments and computational fluid dynamic simulations for 5 and 9 patients, respectively. Cardiac index data were available for all patients. There was no significant difference in the mean and minimum cross-sectional vessel areas of the pulmonary artery between the extracardiac and lateral tunnel groups. The indexed energy dissipation within the total cavopulmonary connection was strongly correlated to minimum cross-sectional area of the pulmonary arteries (R2 value of 0.90 and P < .0002), whereas all other geometric features, including shape characteristics, had no significant correlation. Finally, cardiac index significantly correlated with the minimum pulmonary artery area (P = .006), suggesting that total cavopulmonary connection energy losses significantly affect resting cardiac output.ConclusionsThe minimum outlet size of the total cavopulmonary connection (ie, minimum cross section of pulmonary artery) governs the energy loss characteristics of the total cavopulmonary connection more strongly than variations in the shapes corresponding to extracardiac and lateral tunnel configurations. Differences in pulmonary artery sizes must be accounted for when comparing energy losses between extracardiac and lateral tunnel geometries.

Survival of patients with congenital heart disease has improved such that there are now more adults than children living with these conditions. Complex single ventricle congenital heart disease requiring Fontan palliation is associated with multiple risk factors for impaired bone accrual. Bone density and structure have not been characterized in these patients.Tibia peripheral quantitative computed tomography (pQCT) was used to assess trabecular and cortical volumetric bone mineral density (vBMD), cortical dimensions, and calf muscle area in 43 Fontan participants (5-33 years old), a median of 10 years following Fontan palliation. pQCT outcomes were converted to sex- and race-specific Z-scores relative to age based on700 healthy reference participants. Cortical dimensions and muscle area were further adjusted for tibia length.Height Z-scores were lower in Fontan compared to reference participants (mean ± SD: -0.29 ± 1.00 vs. 0.25 ± 0.93, p0.001); BMI Z-scores were similar (0.16 ± 0.88 vs. 0.35 ± 1.02, p = 0.1). Fontan participants had lower trabecular vBMD Z-scores (-0.85 ± 0.96 vs. 0.01 ± 1.02, p0.001); cortical vBMD Z-scores were similar (-0.17 ± 0.98 vs. 0.00 ± 1.00, p = 0.27). Cortical dimensions were reduced with lower cortical area (-0.59 ± 0.84 vs. 0.00 ± 0.88, p0.001) and periosteal circumference (-0.50 ± 0.82 vs. 0.00 ± 0.84, p0.001) Z-scores, compared to reference participants. Calf muscle area Z-scores were lower in the Fontan participants (-0.45 ± 0.98 vs. 0.00 ± 0.96, p = 0.003) and lower calf muscle area Z-scores were associated with smaller periosteal circumference Z-scores (R = 0.62, p0.001). Musculoskeletal deficits were not associated with age, Fontan characteristics, parathyroid hormone or vitamin D levels.Children and young adults demonstrate low trabecular vBMD, cortical structure and muscle area following Fontan. Muscle deficits were associated with smaller periosteal dimensions. Future studies should determine the fracture implications of these deficits and identify interventions to promote musculoskeletal development.

The investigators recently validated a method of quantifying systemic-to-pulmonary arterial collateral flow using phase-contrast magnetic resonance imaging velocity mapping. Cross-sectional data suggest decreased collateral flow in patients with total cavopulmonary connections (TCPCs) compared with those with superior cavopulmonary connections (SCPCs). However, no studies have examined serial changes in collateral flow from SCPCs to TCPCs in the same patients. The aim of this study was to examine differences in collateral flow between patients with SCPCs and those with TCPCs. Collateral flow was quantified by 2 independent measures from 250 single-ventricle studies in 219 different patients (115 SCPC and 135 TCPC studies, 31 patients with both) and 18 controls, during routine studies using through-plane phase-contrast magnetic resonance imaging. Collateral flow was indexed to body surface area, aortic flow, and pulmonary venous flow. Regardless of indexing method, SCPC patients had significantly higher collateral flow than TCPC patients (1.64 ± 0.8 vs 1.03 ± 0.8 L/min/m(2), p0.001). In 31 patients who underwent serial examinations, collateral flow as a fraction of aortic flow increased early after TCPC completion. In TCPC patients, indexed collateral flow demonstrated a significant negative correlation with time from TCPC. In conclusion, SCPC and TCPC patients demonstrate substantial collateral flow, with SCPC patients having higher collateral flow than TCPC patients overall. On the basis of the paired subset analysis, collateral flow does not decrease in the short term after TCPC completion and trends toward an increase. In the long term, however, collateral flow decreases over time after TCPC completion.

Systemic to pulmonary arterial collateral flow (CollF) is common in single ventricle patients with superior cavopulmonary connections (SCPC), although associations with CollF are not well understood. We previously described a method to quantify CollF by cardiac MRI (CMR). We sought to identify factors associated with CollF in a large cross section of patients with SCPC.A retrospective observational cohort study of events from birth to study CMR was performed for all patients with SCPC who had CollF quantified by CMR.CollF was quantified in 96 patients at a median age of 2.6 (IQR 1.9-3.1) years and 2.1 (1.4-2.7) years after SCPC and measured 1.6±0.7 L/min/m(2) (33±11% of aortic flow and 48±16% of pulmonary venous flow). Significantly higher amounts of indices of CollF were associated with: duration of chest tubes (p≤0.05 for all), intensive care unit and hospital length of stay (p≤0.04 for all), higher O2 saturation at Stage 2 discharge (p=0.04 for CollF/aortic), female sex (p≤0.007 for CollF/aortic and CollF/pulmonary venous), and history of a Blalock-Taussig shunt (p0.04 for CollF and CollF/aortic). Multivariable models were constructed to identify factors independently associated with CollF measures and included: female sex (p≤0.006 for all), O2 saturation at Stage 2 discharge (p=0.013 for CollF/aortic) and total chest tube days (p=0.001 for all). These models explained 20-22% of the variance in the outcomes.These data support hypotheses that perioperative morbidity and pleural inflammation play a role in CollF development and that CollF affects pulmonary blood flow.

Background Single ventricle lesions are associated with gradual attrition after surgical palliation with the total cavopulmonary connection (TCPC). Ventricular dysfunction is frequently noted, particularly impaired diastolic performance. This study seeks to relate TCPC hemodynamic energy losses to single ventricle volumes and filling characteristics. Methods Cardiac magnetic resonance (CMR) data were retrospectively analyzed for 30 single ventricle patients at an average age of 12.7 ± 4.8 years. Cine ventricular short-axis scans were semiautomatically segmented for all cardiac phases. Ventricular volumes, ejection fraction, peak filling rate, peak ejection rate, and time to peak filling were calculated. Corresponding patient-specific TCPC geometry was acquired from a stack of transverse CMR images; relevant flow rates were segmented from through-plane phase contrast CMR data at TCPC inlets and outlets. The TCPC indexed power loss was calculated from computational fluid dynamics simulations using a validated custom solver. Time-averaged flow conditions and rigid vessel walls were assumed in all cases. Pearson correlations were used to detect relationships between variables, with p less than 0.05 considered significant. Results Ventricular end-diastolic (R = −0.48) and stroke volumes (R = −0.37) had significant negative correlations with the natural logarithm of a flow-independent measure of power loss. This power loss measure also had a significant positive relationship to time to peak filling rate (normalized to cycle time; R = 0.67). Conclusions Flow-independent TCPC power loss is inversely related with ventricular end-diastolic and stroke volumes. Elevated power losses may contribute to impaired diastolic filling and limited preload reserve in single ventricle patients.

Anomalous left coronary artery from the inappropriate aortic sinus with intraseptal course is generally benign but can be confused on imaging studies with the potentially lethal interarterial, intramural anomalous left coronary artery. The purpose of this study was to assess normal ostial morphologic features and intraseptal course using cardiac MRI and CT in pediatric patients with intraseptal anomalous left coronary artery.A retrospective review was conducted of the medical records of 14 children with the diagnosis of intraseptal anomalous left coronary artery between November 2009 and March 2013. Coronary artery origin and course were evaluated with cardiac MRI or CT, and 3D assessment of coronary ostial morphologic features was performed with virtual angioscopy.The patient ages ranged from 5 to 18 years at diagnosis; 10 (71.4%) were boys. The right and left coronary origins were the right sinus of Valsalva as a common origin (n = 9) or a single coronary artery (n = 5). Anomalous intraseptal left main coronary was found in 13 patients, and one patient had anomalous left anterior descending with retroaortic circumflex coronary artery. Anomalous coronary ostia were round and without stenosis in all studies. The anomalous vessel was identified with echocardiography, but the anomalous left coronary artery was not delineated, and a normal ostium was not adequately portrayed in any instance.By use of cardiac MRI and CT, the anomalous course of round coronary ostia was confirmed and visualized in a pediatric cohort with intraseptal anomalous left coronary artery. The data provide the basis for understanding the benign clinical course and showing that surgery is unnecessary for this coronary anomaly.

In postoperative congenital heart patients with pulmonary regurgitation, individual branch pulmonary artery regurgitant fractions estimate relative pulmonary vascular resistance independent of pulmonary blood flow distribution.