Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot.

OBJECTIVE: Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF). METHODS: We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment-including blood sampling and speckle tracking echocardiography-occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples. RESULTS: We included 45 patients with ToF repair aged 4.3 (3.4 - 6.5) months and 16 patients with PVR aged 10.4 (7.8 - 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (-18±4 to -13±4 to -20±2, p < 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p < 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients' sex, rather than ToF-related phenotypes in a subset of the study population. CONCLUSIONS: The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury. TRIAL REGISTRATION NUMBER: Netherlands Trial Register: NL5129.

Functional Echocardiographic and Serum Biomarker Changes Following Surgical and Percutaneous Atrial Septal Defect Closure in Children.

Background Ventricular performance is temporarily reduced following surgical atrial septal defect closure. Cardiopulmonary bypass and changes in loading conditions are considered important factors, but this phenomenon is incompletely understood. We aim to characterize biventricular performance following surgical and percutaneous atrial septal defect closure and to relate biomarkers to ventricular performance following intervention. Methods and Results In this multicenter prospective study, children scheduled for surgical or percutaneous atrial septal defect closure were included. Subjects were assessed preoperatively, in the second week postintervention (at 2-weeks follow-up), and 1-year postintervention (1-year follow-up). At each time point, an echocardiographic study and a panel of biomarkers were obtained. Sixty-three patients (median age, 4.1 [interquartile range, 3.1-6.1] years) were included. Forty-three patients underwent surgery. At 2-weeks follow-up, right ventricular global longitudinal strain was decreased for the surgical, but not the percutaneous, group (-17.6±4.1 versus -27.1±3.4; P<0.001). A smaller decrease was noted for left ventricular global longitudinal strain at 2-weeks follow-up for the surgical group (surgical versus percutaneous, -18.6±3.2 versus -20.2±2.4; P=0.040). At 1-year follow-up, left ventricular performance returned to baseline, whereas right ventricular performance improved, but did not reach preintervention levels. Eight biomarkers relating to cardiovascular and immunological processes differed across study time points. Of these biomarkers, only NT-proBNP (N-terminal pro-B-type natriuretic peptide) correlated with less favorable left ventricular global longitudinal strain at 2-weeks follow-up. Conclusions Right, and to a lesser degree left, ventricular performance was reduced early after surgical atrial septal defect closure. Right ventricular performance at 1-year follow-up remained below baseline levels. Several biomarkers showed a pattern over time similar to ventricular performance. These biomarkers may provide insight into the processes that affect ventricular function. Registration URL: https://www.trialregister.nl/; Unique identifier: NL5129.

Associations between blood biomarkers, cardiac function and adverse outcome in a young tetralogy of Fallot cohort.

BACKGROUND: To determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF). METHODS: In the setting of multicenter prospective research studies TOF patients underwent blood sampling, cardiopulmonary exercise testing and low-dose dobutamine stress cardiac magnetic resonance (CMR) imaging. In the blood sample NT-proBNP, GDF-15, Galectin-3, ST-2, DLK-1, FABP4, IGFBP-1, IGFBP-7, MMP-2, and vWF were assessed. During subsequent follow-up, patients were evaluated for reaching the study endpoint (cardiac death, arrhythmia-related hospitalization or cardioversion/ablation, VO2 max ≤65% of predicted). Regression analysis was used to explore the correlation between blood biomarkers (corrected for age and gender) and other clinical parameters. The potential predictive value of blood biomarkers and events were assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: We included 137 Fallot patients, median age 19.2 (interquartile range: 14.6-25.7) years, median age at TOF-repair 0.9 (0.5-1.9) years. After a median follow-up of 8.7 (6.3-10.7) years, 20 (14.6%) patients reached the composite endpoint. In a multivariable cox-regression analysis corrected for age at study baseline, elevated IGFBP-7 and MMP-2 levels were associated with the composite endpoint. We also noted a correlation between DLK-1 and relative change in right ventricular end systolic volume during dobutamine stress CMR (ß = -0.27, p = 0.010), a correlation between FABP4 and Max VO2 (ß = -0.41, p ≤0.001 and between MMP-2 and tricuspid valve E/A ratio (ß = -0.15, p = 0.037). CONCLUSIONS: IGFBP-7, MMP-2 and DLK-1 levels are related to cardiac function and long-term outcome in TOF patients.

Hemodynamic interplay of vorticity, viscous energy loss, and kinetic energy from 4D Flow MRI and link to cardiac function in healthy subjects and Fontan patients.

The purpose of this study was to directly assess (patho)physiology of intraventricular hemodynamic interplay between four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI)-derived vorticity with kinetic energy (KE) and viscous energy loss (EL) over the cardiac cycle and their association to ejection fraction (EF) and stroke volume (SV). Fifteen healthy subjects and thirty Fontan patients underwent whole heart 4D Flow MRI. Ventricular vorticity, KE, and EL were computed over systole (vorticity_volavg systole, KEavg systole, and ELavg systole) and diastole (vorticity_volavg diastole, KEavg diastole, and ELavg diastole). The association between vorticity_vol and KE and EL was tested by Spearman correlation. Fontan patients were grouped to normal and impaired EF groups. A significant correlation was found between SV and vorticity in healthy subjects (systolic: ρ = 0.84, P < 0.001; diastolic: ρ = 0.81, P < 0.001) and in Fontan patients (systolic: ρ = 0.61, P < 0.001; diastolic: ρ = 0.54, P = 0.002). Healthy subjects showed positive correlation between vorticity_vol versus KE (systole: ρ = 0.96, P < 0.001; diastole: ρ = 0.90, P < 0.001) and EL (systole: ρ = 0.85, P < 0.001; diastole: ρ = 0.84, P < 0.001). Fontan patients showed significantly elevated vorticity_vol compared with healthy subjects (vorticity_volavg systole: 3.1 [2.3-3.9] vs. 1.7 [1.3-2.4] L/s, P < 0.001; vorticity_volavg diastole: 3.1 [2.0-3.7] vs. 2.1 [1.6-2.8] L/s, P = 0.002). This elevated vorticity in Fontan patients showed strong association with KE (systole: ρ = 0.91, P < 0.001; diastole: ρ = 0.85, P < 0.001) and EL (systole: ρ = 0.82, P < 0.001; diastole: ρ = 0.89, P < 0.001). Fontan patients with normal EF showed significantly higher vorticity_volavg systole and ELavg systole, but significantly decreased KE avg diastole, in the presence of normal SV, compared with healthy subjects. Healthy subjects show strong physiological hemodynamic interplay between vorticity with KE and EL. Fontan patients demonstrate a pathophysiological hemodynamic interplay characterized by correlation of elevated vorticity with KE and EL in the presence of maintained normal stroke volume. Altered vorticity and energetic hemodynamics are found in the presence of normal EF in Fontan patients.NEW & NOTEWORTHY Physiologic intraventricular hemodynamic interplay/coupling is present in the healthy left ventricle between vorticity versus viscous energy loss and kinetic energy from four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI). Conversely, Fontan patients present compensatory pathophysiologic hemodynamic coupling by an increase in intraventricular vorticity that positively correlates to viscous energy loss and kinetic energy levels in the presence of maintained normal stroke volume. Altered vorticity and energetics are found in the presence of normal ejection fraction in Fontan patients.

Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort.

Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure. Methods and Results In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide), GDF-15 (growth differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after Fontan completion. After this baseline study measurement, follow-up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years, median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2 (4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT-proBNP was associated with (all) events during follow-up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe event-free survival was better in patients with low levels of GDF-15 (P=0.005) and vWF (P=0.008) and high levels of DLK-1 (P=0.041). There was a positive correlation (ß=0.33, P=0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve. Conclusions NT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to long-term outcome in young patients who have undergone the Fontan procedure.

Left and Right Ventricular Impairment Shortly After Correction of Tetralogy of Fallot.

Surgical repair of Tetralogy of Fallot (ToF) is usually performed in the first months of life with low early postoperative mortality. During long-term follow-up, however, both right (RV) and left ventricular (LV) performances may deteriorate. Tissue Doppler imaging (TDI) and speckle tracking echocardiography (ST) can unmask a diminished RV and LV performance. The objective of the current study was to assess the cardiac performance before and shortly after corrective surgery in ToF patients using conventional, TDI and ST echocardiographic techniques. Thirty-six ToF patients after surgery were included. Transthoracic echocardiography including TDI and ST techniques was performed preoperatively and at hospital discharge after surgery (10 days to 4 weeks after surgery). Median age at surgery was 7.5 months [5.5-10.9]. Regarding the LV systolic function there was a significant decrease in interventricular septum (IVS) S' at discharge as compared to preoperatively (pre IVS S' = 5.4 ± 1.4; post IVS S' = 3.9 ± 1.2; p < 0.001) and in global longitudinal peak strain (GLS) (pre = - 18.3 ± 3.4; post = - 14.2 ± 4.1; p = 0.003); but not in the fractional shortening (FS). Both conventional and TDI parameters showed a decrease in diastolic function at discharge. Tricuspid Annular Plane Systolic Excursion and RV S' were significantly lower before discharge. When assessing the RV diastolic performance, only the TDI demonstrated a RV impairment. There was a negative correlation between age at surgery and postoperative LV GLS (R = - 0.41, p = 0.031). There seems to be an impairment in left and right ventricle performance at discharge after ToF corrective surgery compared to preoperatively. This is better determined with TDI and ST strain imaging than with conventional echocardiography.

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VO2max in Fontan patients.

BACKGROUND: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity. METHODS: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 µg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_volavg cycle, KEavg cycle, ELavg cycle). The relation to maximum oxygen uptake (VO2 max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data. RESULTS: Dobutamine stress caused a significant 88 ± 52% increase in KE (KEavg cycle: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (ELavg cycle: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_volavg cycle: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO2 max (KEavg cycle: r = - 0.83, P = 0.003; ELavg cycle: r = - 0.80, P = 0.006; vorticity_volavg cycle: r = - 0.64, P = 0.047). CONCLUSIONS: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO2 max.

Electrical remodeling after percutaneous atrial septal defect closure in pediatric and adult patients.

BACKGROUND: Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients. METHODS: ECGs of 69 children and 75 adults (median age 6 [IQR 4-11] years and 45 [IQR 33-54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1-7 days), intermediate (4-14 weeks) and late (6-18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms. RESULTS: In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children. CONCLUSION: In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure.

Disproportionate intraventricular viscous energy loss in Fontan patients: analysis by 4D flow MRI.

AIMS: To non-invasively assess intraventricular viscous energy loss (EL) and proportionality to kinetic energy (KE) in Fontan patients using 4D flow magnetic resonance imaging (MRI) and compare to healthy controls. METHODS AND RESULTS: Thirty Fontan patients and 15 controls underwent 4D flow MRI. Ventricular EL was computed and normalized by end-diastolic volume (EDV). EL over the cardiac cycle (ELcycle) relative to the average kinetic energy (KEcycle) was quantified using a dimensionless index, ELindex (ELcycle/KEcycle). EL was significantly elevated in Fontan patients compared to controls (ELcycle/EDV: 3.7 vs. 2.6 J/m3, P = 0.001). Fontan patients with inflow of blood entering a ventricle, which leaves that ventricle through a ventricular septal defect to the aorta, defined as discordant inflow-to-outflow showed significantly higher EL compared to patients with inflow of blood into the same ventricle from which the blood is ejected into the aorta, defined as concordant inflow-to-outflow (ELcycle/EDV: 6.8 vs. 3.2 J/m3, P = 0.001). EL was not significantly different in Fontan patients with a systemic left vs. a systemic right ventricle (ELcycle/EDV: 3.5 vs. 3.6 J/m3, P = 0.91). ELindex was significantly elevated in Fontan patients compared to controls (ELindex: 0.4 vs. 0.2, P < 0.001). Highest ELindex was found in Fontan patients with discordant inflow-to-outflow compared to concordant inflow-to-outflow (0.5 vs. 0.3, P = 0.01). CONCLUSION: Fontan patients show disproportionate intraventricular EL relative to KE. Intraventricular EL is elevated in these patients compared to healthy controls, and highest EL is found in patients with discordant inflow-to-outflow.

Automated Cardiac Valve Tracking for Flow Quantification with Four-dimensional Flow MRI.

Purpose To compare four-dimensional flow MRI with automated valve tracking to manual valve tracking in patients with acquired or congenital heart disease and healthy volunteers. Materials and Methods In this retrospective study, data were collected from 114 patients and 46 volunteers who underwent four-dimensional flow MRI at 1.5 T or 3.0 T from 2006 through 2017. Among the 114 patients, 33 had acquired and 81 had congenital heart disease (median age, 17 years; interquartile range [IQR], 13-49 years), 51 (45%) were women, and 63 (55%) were men. Among the 46 volunteers (median age, 28 years; IQR, 22-36 years), there were 19 (41%) women and 27 (59%) men. Two orthogonal cine views of each valve were used for valve tracking. Wilcoxon signed-rank test was used to compare analysis times, net forward volumes (NFVs), and regurgitant fractions. Intra- and interobserver variability was tested by using intraclass correlation coefficients (ICCs). Results Analysis time was shorter for automated versus manual tracking (all patients, 14 minutes [IQR, 12-15 minutes] vs 25 minutes [IQR, 20-25 minutes]; P < .001). Although overall differences in NFV and regurgitant fraction were comparable between both methods, NFV variation over four valves was smaller for automated versus manual tracking (all patients, 4.9% [IQR, 3.3%-6.7%] vs 9.8% [IQR, 5.1%-14.7%], respectively; P < .001). Regurgitation severity was discordant for seven pulmonary valves, 22 mitral valves, and 21 tricuspid valves. Intra- and interobserver agreement for automated tracking was excellent for NFV assessment (intra- and interobserver, ICC ≥ 0.99) and strong to excellent for regurgitant fraction assessment (intraobserver, ICC ≥ 0.94; interobserver, ICC ≥ 0.89). Conclusion Automated valve tracking reduces analysis time and improves reliability of valvular flow quantification with four-dimensional flow MRI in patients with acquired or congenital heart disease and in healthy volunteers. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by François in this issue.

Four-dimensional flow magnetic resonance imaging-derived blood flow energetics of the inferior vena cava-to-extracardiac conduit junction in Fontan patients.

OBJECTIVES: In patients with the Fontan circulation, systemic venous return flows passively towards the lungs. Because of the absence of the subpulmonary ventricle, favourable blood flow patterns with minimal energy loss are clinically relevant. The region where the inferior vena cava, the hepatic veins and the extracardiac conduit join (IVC-conduit junction) is a potential source of increased energy loss. The aim of this study was to evaluate the relationship between geometry and blood flow patterns in the IVC-conduit junction with associated kinetic energy and energy loss using 4-dimensional flow magnetic resonance imaging (MRI). METHODS: Fourteen extracardiac conduit-Fontan patients underwent 4-dimensional flow MRI. The IVC-conduit junctions were ranked into 3 groups for 3 categories: the geometry, the flow complexity and the conduit mean velocity. The relative increase in the mean velocity from the IVC to the conduit (representing IVC-conduit mismatch) was determined. The peak kinetic energy and mean kinetic energy and energy loss were determined and normalized for volume. RESULTS: In 4 of 14 patients, adverse geometries led to helical flow patterns and/or acute changes in flow direction. For each category, the most adverse IVC-conduit junctions were associated with an approximate 2.3-3.2-fold and 2.0-2.9-fold increase in kinetic energy and energy loss, respectively. The IVC-conduit mismatch is strongly correlated with the mean kinetic energy and energy loss (r = 0.80, P = 0.001 and ρ = 0.83, P < 0.001, respectively) and with body surface area in patients with 16- mm conduits (r = 0.88, P = 0.010). CONCLUSIONS: The IVC-conduit junction is a potential source of increased energy loss. Junctions with increased energy loss showed: (i) a distorted geometry leading to adverse blood flow patterns and/or (ii) the IVC-conduit mismatch. Sixteen-millimetre conduits appear to be inadequate for older patients.

Scan-rescan reproducibility of diastolic left ventricular kinetic energy, viscous energy loss and vorticity assessment using 4D flow MRI: analysis in healthy subjects.

The aim of the current study was to assess the scan-rescan reproducibility of left ventricular (LV) kinetic energy (KE), viscous energy loss (EL) and vorticity during diastole from four-dimensional flow magnetic resonance imaging (4D flow MRI) in healthy subjects. Twelve volunteers (age 27 ± 3 years) underwent whole-heart 4D flow MRI twice in one session. In-scan consistency was evaluated by correlation between KE and EL. ELindex was computed to measure the amount of EL relative to KE over diastole. Scan-rescan analysis was performed to test reproducibility of volumetric measurements of KE, EL, ELindex and vorticity in the LV over early (E) and late (A) diastolic filling. In-scan consistency between KE and EL was strong-excellent (E-filling scan1: r = 0.92, P < 0.001; scan2: ρ = 0.96, P < 0.001 and A-filling scan1: ρ = 0.87, P < 0.001; scan2: r = 0.99, P < 0.001). For the majority of subjects (10 out of 12), KE and EL measures showed good to strong reproducibility. However, with a wide range of agreement [intraclass correlation (ICC): 0.64-0.95] and coefficients of variation (CV) ≤ 25%. ELindex showed strong reproducibility for all 12 subjects with a strong ICC (0.94, P < 0.001) and a CV of 9%. Scan-rescan reproducibility of volumetric vorticity showed good-excellent ICCs (0.83-0.95) with CVs ≤ 11%. In conclusion, the current study shows strong-excellent in-scan consistency and overall good agreement between scans for 4D flow MRI assessment of left ventricular kinetic energy, energy loss and vorticity over diastole. However, substantial differences between the scans were also found in some parameters in two out of twelve subjects. Strong reproducibility was found in the dimensionless ELindex, which measures the amount of viscous energy loss relative to the average kinetic energy over diastole.

Normal values of the ventricular gradient and QRS-T angle, derived from the pediatric electrocardiogram.

BACKGROUND: Normal values of the mathematically-synthesized vectorcardiogram (VCG) are lacking for children. Therefore, the objective of this study was to assess normal values of the pediatric synthesized VCG (spatial QRS-T angle [SA] and ventricular gradient [VG]). METHODS: Electrocardiograms (ECGs) of 1263 subjects (0-24 years) with a normal heart were retrospectively selected. VCGs were synthesized by the Kors matrix. Normal values (presented as 2nd and 98th percentiles) were assessed by quantile regression with smoothing by splines. RESULTS: Our results show that heart rate decreased over age, QRS duration increased and QTc interval remained constant. The SA initially decreased and increased again from the age of 8 years. The VG magnitude was relatively stable until the age of 2 years, after which it increased. CONCLUSION: Normal values of the pediatric ECG and VCG (VG and SA) were established. These normal values could be important for future studies using VG and SA for risk stratification in heart disease in children.

In-scan and scan-rescan assessment of LV in- and outflow volumes by 4D flow MRI versus 2D planimetry.

PURPOSE: To evaluate the in-scan and scan-rescan consistency of left ventricular (LV) in- and outflow assessment from 1) 2D planimetry; 2) 4D flow magnetic resonance imaging (MRI) with retrospective valve tracking, and 3) 4D flow MRI with particle tracing. MATERIALS AND METHODS: Ten healthy volunteers (age 27 ± 3 years) underwent multislice cine short-axis planimetry and whole-heart 4D flow MRI on a 3T MRI scanner twice with repositioning between the scans. LV in- and outflow was compared from 1) 2D planimetry; 2) 4D flow MRI with retrospective valve tracking over the mitral valve (MV) and aortic valve (AV), and 3) 4D flow MRI with particle tracing through forward and backward integration of velocity data. RESULTS: In-scan consistency between MV and AV flow volumes is excellent for both 4D flow MRI methods with r ≥ 0.95 (P ≤ 0.001). In-scan AV and MV flow by retrospective valve tracking shows good to excellent correlations versus AV and MV flow by particle tracing (r ≥ 0.81, P ≤ 0.004). Scan-rescan SV assessment by 2D planimetry shows excellent reproducibility (intraclass correlation [ICC] = 0.98, P < 0.001, coefficient of variation [CV] = 7%). Scan-rescan MV and AV flow volume assessment by retrospective valve tracking shows strong reproducibility (ICCs ≥ 0.89, P ≤ 0.05, CVs = 12%), as well as by forward and backward particle tracing (ICCs ≥ 0.90, P ≤ 0.001, CVs ≤ 11%). Multicomponent particle tracing shows good scan-rescan reproducibility (ICCs ≥ 0.81, P ≤ 0.007, CVs ≤ 16%). CONCLUSION: LV in- and outflow assessment by 2D planimetry and 4D flow MRI with retrospective valve tracking and particle tracing show good in-scan consistency and strong scan-rescan reproducibility, which indicates that both 4D flow MRI methods are reliable and can be used clinically. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:511-522.

Unravelling cardiovascular disease using four dimensional flow cardiovascular magnetic resonance.

Knowledge of normal and abnormal flow patterns in the human cardiovascular system increases our understanding of normal physiology and may help unravel the complex pathophysiological mechanisms leading to cardiovascular disease. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has emerged as a suitable technique that enables visualization of in vivo blood flow patterns and quantification of parameters that could potentially be of prognostic value in the disease process. In this review, current image processing tools that are used for comprehensive visualization and quantification of blood flow and energy distribution in the heart and great vessels will be discussed. Also, imaging biomarkers extracted from 4D flow CMR will be reviewed that have been shown to distinguish between normal and abnormal flow patterns. Furthermore, current applications of 4D flow CMR in the heart and great vessels will be discussed, showing its potential as an additional diagnostic modality which could aid in disease management and timing of surgical intervention.

Comparison of model-based and expert-rule based electrocardiographic identification of the culprit artery in patients with acute coronary syndrome.

BACKGROUND AND PURPOSE: Culprit coronary artery assessment in the triage ECG of patients with suspected acute coronary syndrome (ACS) is relevant a priori knowledge preceding percutaneous coronary intervention (PCI). We compared a model-based automated method (Olson method) with an expert-rule based method for the culprit artery assessment. METHODS: In each of the 53 patients who were admitted with the working diagnosis of suspected ACS, scheduled for emergent angiography with a view on revascularization as initial treatment and subsequently found to have an angiographically documented completely occluded culprit artery, culprit artery location was assessed in the preceding ECG by both the model-based Olson method and the expert-rule based method that considered either visual or computer-measured J-point amplitudes. ECG culprit artery estimations were compared with the angiographic culprit lesion locations. Proportions of correct classifications were compared by a Z test at the 5% significance level. RESULTS: The Olson method performed slightly, but not significantly, better, when the expert-rule based method used visual assessment of J-point amplitudes (88.7% versus 81.1% correct; P=0.28). However, the Olson method performed significantly better when the expert-rule based method used computer-measured J-point amplitudes (88.7% versus 71.7% correct; P<0.05). CONCLUSION: The automated model-based Olson method performed at least at the level of expert cardiologists using a manual rule-based method.

Bilateral Heel Numbness due to External Compression during Obstetric Epidural Analgesia.

We describe the case of a 32-year-old woman who developed bilateral heel numbness after obstetric epidural analgesia. We diagnosed her with bilateral neuropathy of the medial calcaneal nerve, most likely due to longstanding pressure on both heels. Risk factors for the development of this neuropathy were prolonged labour with spinal analgesia and a continuation of analgesia during episiotomy. Padded footrests decrease pressure and can possibly prevent this neuropathy.