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Aims Inefficient ventricular–arterial (V–A) coupling has been described in Fontan patients and may result in adverse haemodynamics. A varying amount of aortopulmonary collateral (APC) flow is also frequently present that increases volume load of the single ventricle. The aim of the study was to assess changes in V–A coupling and APC flow during exercise CMR. Methods and results Eighteen Fontan patients (age 24 ± 3 years) and 14 controls (age 23 ± 4 years) underwent exercise CMR using a cycle ergometer. Ventricular volumetry and flow measurements in the ascending aorta (AAO), inferior (IVC), and superior (SVC) vena cava were assessed using real-time sequences during stepwise increases in work load. Measures of systemic arterial elastance Ea, ventricular elastance Ees, and V–A coupling (Ea/Ees) were assessed. APC flow was quantified as AAO − (SVC + IVC). Ea remained unchanged during all levels of exercise in both groups (P = 0.39 and P = 0.11). Ees increased in both groups (P = 0.001 and P < 0.001) with exercise but was lower in the Fontan group (P = 0.04). V–A coupling was impaired in Fontan patients at baseline (P = 0.04). Despite improvement during exercise (P = 0.002) V–A coupling remained impaired compared with controls (P = 0.001). Absolute APC flow in Fontan patients did not change during exercise even at maximum work load (P = 0.98). Conclusions Inefficient V–A coupling was already present at rest in Fontan patients and aggravated during exercise due to a limited increase in ventricular contractility which demonstrates the importance of a limited functional reserve of the single ventricle. APC flow remained unchanged suggesting no further increase in volume load during exercise.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is widely used for aortic diameter assessment but there is no consensus on the sequence or cardiac cycle phase in which the measures should be taken. The most used sequence is contrast-enhanced-magnetic-resonance-angiography (angiography), usually non-ECG-triggered. An alternative is a navigated 3D-whole-heart-steady-state-free-precession sequence which is contrast-free and breath- and ECG-gated (mostly diastolic gating), producing very sharp anatomical rendering. Nonetheless, its routine use has not yet spread. Our aim was evaluating aortic diameters by a systolic-gated 3D and put additional effort in the validation of diastolic-gated 3D as alternative to angiography. METHODS: We retrospectively analysed 30 patients scheduled for routine Angiography. We measured the aorta at 9 standard positions by three different sequences (angiography, 3D-diastole and 3D-systole) and compared the diameters obtained by calculating the differences and by paired t-test analysis. RESULTS: Diameters by 3D-systole were larger than by 3D-diastole and angiography (P

Background: Diastolic pulmonary arterial pressure (dPAP) is regarded to be less sensitive to flow metrics as compared to mean PAP (mPAP), and was therefore proposed for the assessment of a precapillary component in patients with postcapillary pulmonary hypertension (PH). To analyze the diagnostic and prognostic impact of dPAP in patients with pure precapillary PH, we purposed to compare the correlation between dPAP and mPAP, as well as hemodynamically-derived calculations [ratio of PAP to systemic arterial pressure (PAP/SAP), pulmonary vascular resistance index (PVRI), transpulmonary gradient (TPG)], using both dPAP and mPAP, at rest and during acute vasoreactivity testing (AVT) in children with idiopathic or heritable pulmonary arterial hypertension (IPAH/HPAH). Furthermore, we aimed to assess the association of these metrics (at baseline and changes after AVT) with transplant-free survival.Methods: We conducted a retrospective analysis of the TOPP (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) registry including 246 IPAH/HPAH patients. Of these, 45 children (18.3%) died, and 13 (5.3%) received lung transplantation during the observation period.Results: dPAP and mPAP-derived variables showed almost linear relationship. Higher mPAP/mSAP, and dPAP-/mPAP-derived PVRI at rest was associated with time to death/transplantation. At maximum AVT-response, the decrease of dPAP and mPAP, diastolic pulmonary gradient (DPG) and TPG, as well as dPAP/dSAP and mPAP/mSAP was associated with time to death/transplantation, showing higher significance than corresponding baseline values. Remarkably, no predictive value was found for PVRI-reduction during AVT, neither dPAP- nor mPAP-derived.Conclusions: There is a strong relationship between dPAP and mPAP-derived variables. According to our results, hemodynamics during AVT (irrespectively of dPAP- or mPAP-derived) may have more prognostic implications than resting hemodynamics in children with IPAH/HPAH, except for PVRI.

The heart should not be divided in right and left, whether in health nor in disease. However, the morphological and functional differences between the right and left ventricle should be known and the impact of the ventricle's position considered. Further, the parameters beyond heart rate, contractility, pre- and afterload guaranteeing a sufficient systemic cardiac output have to be integrated in therapeutic measures; preferentially the influence of interventricular mechanics. Despite of recent developments of specific drug therapies, heart failure is associated with a high rate of morbidity and mortality in children. During the progression of heart failure, pulmonary vascular disease is the consequence or the reason for further failing. Clinical symptoms are associated with congestion and low cardiac output at rest or exercise. Improved understanding of the pathophysiological mechanisms particularly of ventricular failure has resulted in the development of innovative therapies that target atrial/ventricular/arterial interactions. Recent advances in interventional and surgical approaches provide promising new strategies to deal with right and left ventricular deterioration. These techniques may delay listing for heart and (heart-) lung transplantation or even make redundant in individual cases. The beneficial effects of these ventricular interaction strategies are mainly based on the mechanics of the interventricular septum and improvement of systolic and diastolic ventricular performance.

BackgroundPaediatric hypertrophic cardiomyopathy (HCM) caused by sarcomere protein gene mutations is more common than previously thought. We present the case of a 9-year-old boy that was diagnosed with HCM during family screening.Case summaryWe present a case of a 9-year-old boy with a family history of sarcomeric HCM who was diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) during clinical screening. Echocardiography and cardiovascular magnetic resonance imaging revealed asymmetric left ventricular hypertrophy with a maximum wall thickness of 18–19 mm. Cardiovascular magnetic resonance late gadolinium enhancement imaging showed patchy fibrosis within the area of maximum wall thickness. Genetic testing confirmed the presence of the familial mutation in the MYL2 gene. The patient was started on bisoprolol. Furthermore, risk stratification was performed and a recommendation for implantable cardioverter-defibrillator implantation was made.DiscussionThis case demonstrates that significant HCM can already start in childhood and discusses the recommendations for family screening on the basis of recently published studies and the present European Society of Cardiology guideline.

Background Long-term course after atrial switch operation is determined by increasing right ventricular (RV) insufficiency. The aim of our study was to investigate subtle functional parameters by invasive measurements with conductance technique and noninvasive examinations with cardiac magnetic resonance imaging (CMR). Methods We used invasive (pressure–volume loops under baseline conditions and dobutamine) and noninvasive techniques (CMR with feature tracking [FT] method) to evaluate RV function. All patients had cardiopulmonary exercise testing (CPET). Results From 2011 to 2013, 16 patients aged 28.2 ± 7.3 (22–50) years after atrial switch surgery (87.5% Senning and 12.5% Mustard) were enrolled in this prospective study. All patients were in New York Heart Association (NYHA) class I to II and presented mean peak oxygen consumption of 30.1 ± 5.7 (22.7–45.5) mL/kg/min. CMR-derived end-diastolic volume was 110 ± 22 (78–156) mL/m2 and RV ejection fraction 41 ± 8% (25–52%). CMR-FT revealed lower global systolic longitudinal, radial, and circumferential strain for the systemic RV compared with the subpulmonary left ventricle. End-systolic elastance (Ees) was overall reduced (compared with data from the literature) and showed significant increase under dobutamine (0.80 ± 0.44 to 1.89 ± 0.72 mm Hg/mL, p ≤ 0.001), whereas end-diastolic elastance (Eed) was not significantly influenced (0.11 ± 0.70 to 0.13 ± 0.15 mm Hg/mL, p = 0.454). We found no relevant relationship between load-independent conductance indices and strain or CPET parameters. Conductance analysis revealed significant mechanical dyssynchrony, higher during diastole (mean 30 ± 4% baseline, 24 ± 6% dobutamine) than during systole (mean 17 ± 6% baseline, 19 ± 7% dobutamine). Conclusions Functional assessment of a deteriorating systemic RV remains demanding. Conductance indices as well as the CMR-derived strain parameters showed overall reduced values, but a significant relationship was not present (including CPET). Our conductance analysis revealed intraventricular and predominantly diastolic RV dyssynchrony.

Background Single ventricle (SV) patients with a Fontan circulation are at risk for functional deterioration. The aim of this study was to assess longitudinal Fontan hemodynamics using serial cardiovascular magnetic resonance (CMR) data and to study the impact of aortopulmonary collateral (APC) flow and type of SV morphology. Methods Forty-one Fontan patients (age at first CMR 13.4 ± 6.0 years) with two CMR examinations within a time interval of at least 4 years (follow-up 5.3 ± 0.9 years) were included. The protocol consisted of short-axis cine volumetry and 2-dimensional blood flow measurements in the inferior vena cava (IVC), superior vena cava (SVC) and ascending aorta (Ao). APC flow was calculated as Ao – (SVC + IVC). Myocardial strain/strain rate was assessed using feature tracking technique. Results SV end-diastolic volume (p = 0.14) and ejection fraction (p = 0.70) remained constant. No significant changes in CMR derived myocardial strain/strain rate values were observed. Ao flow decreased (p = 0.01), IVC flow remained unchanged (p = 0.52), while SVC flow (p = 0.003) and APC flow (p = 0.006) decreased significantly. Patients with a systemic right ventricle (RV) showed unchanged APC flow and a further increase in SV size over time compared to patients with a systemic left ventricle. Conclusions Longitudinal CMR data in a cohort of clinically stable Fontan patients revealed no significant changes in SV dimensions and myocardial performance while APC flow decreased spontaneously. Patients with a systemic RV seem to be at risk for permanent SV volume overload through APCs and might therefore benefit from consequent interventional APC embolization.

Sudden cardiac death (SCD) is the most common cause of late mortality in tetralogy of Fallot (TOF). Pulmonary regurgitation (PR) was previously found to be the most common hemodynamic abnormality associated with ventricular arrhythmias (VA), but cardiovascular magnetic resonance (CMR)-based studies did not show this association. The aim of this study is to investigate the risk factors for VA in TOF using CMR. Electronic records of TOF patients and their CMR studies between July 2006 and October 2018 in one center were retrospectively reviewed. Demographic, clinical and CMR data of patients were collected. Outcome was defined as sustained ventricular tachycardia (VT), aborted SCD and SCD. From a total of 434 TOF patients with complete CMR studies, 19 (4.4%) patients developed a positive outcome (12 sustained VT, 4 aborted SCD, 3 SCD) at a median age of 24 years. The number of surgical interventions was significantly greater in patients who developed VA. Right ventricular volumes were significantly larger in patients who suffered a positive outcome. Odds ratio for developing VA was 6.905 for RVEDVI ≥ 160 ml/m2 and 6.141 for RVESVI ≥ 80 ml/m2 (P = 0.0014 and 0.0012, respectively). Event-free survival was longer in patients with smaller right ventricular volumes. In conclusion, right ventricular dimensions are the most significant factors associated with the development of VA in TOF. The number of surgical interventions is also related to an increased risk.

Introduction: “Le Coeur en Sabot” (or the boot-shaped heart) is a radiological description of the appearance of the heart on a plain radiograph of a patient with Tetralogy of Fallot. This highlights the importance of the shape of the heart. Maladaptive remodeling is known to occur in patients with repaired Tetralogy of Fallot (rToF) due to residual lesions such as Pulmonary Regurgitant Fraction (PRF) Hypothesis: Shape and function analysis can reveal novel remodeling patterns associated with adverse events in patients with rToF Methods: Biventricular shape and function were studied in 192 patients with rToF (median age 15 years). Linear discriminative analysis (LDA) and principal component analysis (PCA) were used to identify shape differences between patients with and without adverse events (AE). AE included death, arrhythmias, and cardiac arrest (median follow-up 10 years) Results: LDA and PCA showed that shape characteristics pertaining to adverse events included a more circular LV (decreased eccentricity), dilated (increased sphericity) LV base, increased RV apical sphericity, and decreased RV basal sphericity. Multivariate LDA showed that the optimal discriminative model included only RV apical ejection fraction and one PCA mode associated with a more circular and dilated LV base (AUC = 0.78). PRF did not add value, and shape changes associated with increased PRF were not predictive of AE. Conclusions: Remodeling patterns in patients with rToF are associated with AE, independent of PRF. Mechanisms leading to AE include LV basal dilation with a reduced RV apical ejection fraction. That is to say that the old descriptor, “Le Coeur en Sabot'' may also describe that shape that is adverse in rTOF. The toe of this boot would be the dilated and poorly contractile RV apex and the ankle would be the spherical LV base (Figure 1: Top Row Diastole. Middle Systole. Posterior projection (a), anatomical position (b) and superior (c). LV is green)

Background Right atrial (RA) dilatation and impaired right ventricular (RV) filling are common in patients with RV outflow tract dysfunction. We aimed to study potential correlations between atrial function with clinically relevant hemodynamic parameters and to assess the predictive impact of atrial performance on the recovery of exercise capacity and RV pump function after percutaneous pulmonary valve implantation (PPVI). Methods and Results Altogether, 105 patients with right ventricular outflow tract dysfunction (median age at PPVI, 19.2 years; range, 6.2–53.4 years) who underwent cardiac magnetic resonance imaging before and 6 months after PPVI were included. RA and left atrial maximal and minimal volumes as well as atrial passive and active emptying function were assessed from axial cine slices. RA emptying function was inversely related to invasive RV end‐diastolic pressure, and RA passive emptying correlated significantly with peak oxygen uptake. After PPVI, a significant decrease in RA minimum volume was observed, whereas RA passive emptying function improved, and RA active emptying function decreased significantly. Patients with predominant right ventricular outflow tract stenosis showed more favorable changes in RA active and left atrial passive emptying than those with primary volume overload. None of the RA and left atrial emptying parameters was predictive for recovery of peak oxygen uptake or RV ejection fraction. Conclusions In patients with right ventricular outflow tract dysfunction, impaired RA emptying assessed by cardiac magnetic resonance imaging was associated with increased RV filling pressures and lower exercise capacity. PPVI leads to a reduction in RA size and improved passive RA emptying function. However, RA function was not associated with improved exercise performance and RV pump function.

Zusammenfassung Eine pathologische Druckerhöhung im pulmonalen Gefäßsystem (pulmonale Hypertonie, PH) wurde bisher definiert durch einen invasiv gemessenen mittleren pulmonalarteriellen Druck (mPAP) ≥25 mm Hg in Ruhe. Auf dem 6th World Symposium on Pulmonary Hypertension (WSPH) in Nizza 2018 wurde eine neue Definition der PH vorgeschlagen, die die Senkung der Obergrenze des normalen mPAP von 24 auf 20 mm Hg beinhaltet. Obwohl keine Evidenz aus pädiatrischen Studien hierfür vorliegt, wurde diese neue PH-Definition (mPAP >20 mm Hg) aus Gründen der Einheitlichkeit auch von der pädiatrischen „Task Force“ des WSPH 2018 übernommen. Die vorliegende Stellungnahme der Arbeitsgemeinschaft Pulmonale Hypertonie (AGPH) der Deutschen Gesellschaft für Pädiatrische Kardiologie und angeborene Herzfehler e. V. (DGPK) erläutert die zugrunde liegende Rationale und mögliche Konsequenzen dieser Definitionsänderung. Insbesondere stellt sie klar, dass diese Änderung der Definition aktuell keinen Einfluss auf die Verschreibung von Medikamenten zur gezielten spezifischen Therapie der pulmonalarteriellen Hypertonie hat.

BACKGROUND Alterations in wall shear stress (WSS) assessed using 4D flow MRI have been shown to play a role in various vascular pathologies, such as bicuspid aortic valve aortopathy. Most studies have focused on systolic WSS, whereas altered diastolic hemodynamics in regurgitant semilunar valvular lesions have not so far been well characterized. PURPOSE To investigate diastolic WSS in aortic and pulmonary regurgitation. STUDY TYPE Retrospective data analysis. POPULATION Thirty tetralogy of Fallot patients, 19 bicuspid aortic valve patients, 11 healthy volunteers. FIELD STRENGTH/SEQUENCE 5 T, 3D time-resolved phase-contrast MRI with 3D velocity encoding. ASSESSMENT Estimation of WSS and its axial and circumferential vector components along cardiac cycle timeframes in the proximal main pulmonary artery in pulmonary regurgitation (PR) and in the proximal ascending aorta in aortic regurgitation (AR) as well as in healthy volunteers. STATISTICAL TESTS Wilcoxon matched pairs test was used for intra-group comparisons and Mann-Whitney test for intergroup comparisons. Correlations were assessed using Spearman correlation. RESULTS WSS along the entire cardiac cycle was higher in PR and AR in comparison with controls (mean WSS 0.381 ± 0.070 vs. 0.220 ± 0.018, P

Anisotropic multi-slice Cardiac Magnetic Resonance (CMR) Images are conventionally acquired in patient-specific short-axis (SAX) orientation. In specific cardiovascular diseases that affect right ventricular (RV) morphology, acquisitions in standard axial (AX) orientation are preferred by some investigators, due to potential superiority in RV volume measurement for treatment planning. Unfortunately, due to the rare occurrence of these diseases, data in this domain is scarce. Recent research in deep learning-based methods mainly focused on SAX CMR images and they had proven to be very successful. In this work, we show that there is a considerable domain shift between AX and SAX images, and therefore, direct application of existing models yield sub-optimal results on AX samples. We propose a novel unsupervised domain adaptation approach, which uses task-related probabilities in an attention mechanism. Beyond that, cycle consistency is imposed on the learned patient-individual 3D rigid transformation to improve stability when automatically re-sampling the AX images to SAX orientations. The network was trained on 122 registered 3D AX-SAX CMR volume pairs from a multi-centric patient cohort. A mean 3D Dice of $0.86\pm{0.06}$ for the left ventricle, $0.65\pm{0.08}$ for the myocardium, and $0.77\pm{0.10}$ for the right ventricle could be achieved. This is an improvement of $25\%$ in Dice for RV in comparison to direct application on axial slices. To conclude, our pre-trained task module has neither seen CMR images nor labels from the target domain, but is able to segment them after the domain gap is reduced. Code: https://github.com/Cardio-AI/3d-mri-domain-adaptation, Accepted for IEEE Transaction on Medical Imaging (TMI) 2021 on 13.01.2021

Planning the optimal time of intervention for pulmonary valve replacement surgery in patients with the congenital heart disease Tetralogy of Fallot (TOF) is mainly based on ventricular volume and function according to current guidelines. Both of these two biomarkers are most reliably assessed by segmentation of 3D cardiac magnetic resonance (CMR) images. In several grand challenges in the last years, U-Net architectures have shown impressive results on the provided data. However, in clinical practice, data sets are more diverse considering individual pathologies and image properties derived from different scanner properties. Additionally, specific training data for complex rare diseases like TOF is scarce. For this work, 1) we assessed the accuracy gap when using a publicly available labelled data set (the Automatic Cardiac Diagnosis Challenge (ACDC) data set) for training and subsequent applying it to CMR data of TOF patients and vice versa and 2) whether we can achieve similar results when applying the model to a more heterogeneous data base. Multiple deep learning models were trained with four-fold cross validation. Afterwards they were evaluated on the respective unseen CMR images from the other collection. Our results confirm that current deep learning models can achieve excellent results (left ventricle dice of $0.951\pm{0.003}$/$0.941\pm{0.007}$ train/validation) within a single data collection. But once they are applied to other pathologies, it becomes apparent how much they overfit to the training pathologies (dice score drops between $0.072\pm{0.001}$ for the left and $0.165\pm{0.001}$ for the right ventricle)., Accepted for SPIE Medical Imaging 2020

Background Patients after aortic coarctation (CoA) repair show impaired aortic bioelasticity and altered left ventricular (LV) mechanics, predisposing diastolic dysfunction. Our purpose was to assess aortic bioelasticity and LV properties in CoA patients who underwent endovascular stenting or surgery using cardiovascular magnetic resonance (CMR) imaging. Methods Fifty CoA patients (20.5 ± 9.5 years) were examined by 3-Tesla CMR. Eighteen patients had previous stent implantation and 32 had surgical repair. We performed volumetric analysis of both ventricles (LV, RV) and left atrium (LA) to measure biventricular volumes, ejection fractions, left atrial (LA) volumes, and functional parameters (LAEFPassive, LAEFContractile, LAEFReservoir). Aortic distensibility and pulse wave velocity (PWV) were assessed. Native T1 mapping was applied to examine LV tissue properties. In twelve patients post-contrast T1 mapping was performed. Results LV, RV and LA parameters did not differ between the surgical and stent group. There was also no significant difference for aortic distensibility, PWV and T1 relaxation times. Aortic root distensibility correlated negatively with age, BMI, BSA and weight (p p p Conclusions CoA patients after surgery or stent implantation did not show significant difference of aortic elasticity. Thus, presumably other factors like intrinsic aortic abnormalities might have a greater impact on aortic elasticity than the approach of repair. Interestingly, our data suggest that native T1 values are influenced by demographic characteristics.

We provide a practical approach on the initial assessment and diagnostic work-up of children and adolescents with pulmonary hypertension (PH). Transthoracic echocardiography (TTE) often serves as initial study tool before invasive cardiac catheterization. Misinterpretation of TTE variables may lead to missed or delayed diagnosis with devastating consequences, or unnecessary invasive diagnostics that have inherited risks. In addition to clinical and biochemical markers, serial examination of patients with PH using a standardized TTE approach, determining conventional and novel echocardiographic variables, may allow early diagnosis and treatment in paediatric PH. Cardiac magnetic resonance imaging and computed tomography represent important non-invasive imaging modalities, that together with TTE may enable comprehensive assessment of ventricular function and pulmonary hemodynamics. Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterization laboratory is still the gold standard for the diagnosis of PH and pulmonary hypertensive vascular disease (PHVD) in children and for the initiation of specific PH therapy. We suggest the regular assessment of prognostic TTE variables as part of a standardized approach for initial diagnosis of children with PH. Overreliance on any single TTE variable should be avoided as it detracts from the overall diagnostic potential of a standardized TTE examination for PH.

The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term "pulmonary hypertension" and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.

BACKGROUND Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function. METHODS Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y). RESULTS LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (β = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance. CONCLUSIONS Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

Alterations in wall shear stress (WSS) assessed using 4D flow MRI have been shown to play a role in various vascular pathologies, such as bicuspid aortic valve aortopathy. Most studies have focused on systolic WSS, whereas altered diastolic hemodynamics in regurgitant semilunar valvular lesions have not so far been well characterized.To investigate diastolic WSS in aortic and pulmonary regurgitation.Retrospective data analysis.Thirty tetralogy of Fallot patients, 19 bicuspid aortic valve patients, 11 healthy volunteers.5 T, 3D time-resolved phase-contrast MRI with 3D velocity encoding.Estimation of WSS and its axial and circumferential vector components along cardiac cycle timeframes in the proximal main pulmonary artery in pulmonary regurgitation (PR) and in the proximal ascending aorta in aortic regurgitation (AR) as well as in healthy volunteers.Wilcoxon matched pairs test was used for intra-group comparisons and Mann-Whitney test for intergroup comparisons. Correlations were assessed using Spearman correlation.WSS along the entire cardiac cycle was higher in PR and AR in comparison with controls (mean WSS 0.381 ± 0.070 vs. 0.220 ± 0.018, P 0.0001; 0.361 ± 0.099 vs. 0.212 ± 0.030, P 0.0001; respectively). Peak diastolic WSS was significantly higher than the mean WSS in AR and PR (P 0.0001-0.005). The severity of PR correlated with the peak diastolic axial WSS (Spearman's rElevated diastolic WSS is a component of the altered flow hemodynamics in AR and PR. This may give more insight into the pathophysiologic role of WSS in vascular remodeling in AR and PR.4 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:763-770.

Invasive hemodynamic studies have shown that nitric oxide (NO), a selective pulmonary vasodilator, can lower pulmonary vascular resistance in Fontan patients. Because oximetry-derived flow quantification may be unreliable, we sought to detect changes in blood flow within the Fontan circulation after inhalation of NO using cardiovascular magnetic resonance (CMR). Thirty-three patients (mean age 12.8 ± 7.0 years) after the Fontan procedure underwent CMR as part of their routine clinical assessment. Standard two-dimensional blood flow measurements were performed in the Fontan tunnel, superior vena cava (SVC) and ascending aorta (AAO) before and after inhalation of 40 ppm NO for 8-10 min. Systemic-to-pulmonary collateral (SPC) flow was calculated as AAO - (SVC + tunnel). Heart rate (82 ± 18 to 81 ± 18 bpm; p = 0.31) and transcutaneous oxygen saturations (93 ± 4 to 94 ± 3 %; p = 0.13) did not change under NO inhalation. AAO flow (3.23 ± 0.72 to 3.12 ± 0.79 l/min/m(2); p = 0.08) decreased, tunnel flow (1.58 ± 0.40 to 1.65 ± 0.46 l/min/m(2); p = 0.032) increased, and SVC flow (1.01 ± 0.39 to 1.02 ± 0.40 l/min/m(2); p = 0.50) remained unchanged resulting in higher total caval flow (Qs) (2.59 ± 0.58 to 2.67 ± 0.68 l/min/m(2); p = 0.038). SPC flow decreased significantly from 0.64 ± 0.52 to 0.45 ± 0.51 l/min/m(2) (p = 0.002) and resulted in a significant decrement of the Qp/Qs ratio (1.23 ± 0.23 to 1.15 ± 0.23; p = 0.001). Inhalation of NO in Fontan patients results in significant changes in pulmonary and systemic blood flow. The reduction in SPC flow is accompanied by a net increase in effective systemic blood flow suggesting beneficial effects of pulmonary vasodilators on cardiac output, tissue perfusion and exercise capacity.

Aims: To quantitatively evaluate the basic pathophysiological process involved in the creation of Eisenmenger syndrome in pediatric pulmonary arterial hypertension (PAH) patients by either atrial septostomy (AS) or Potts shunt (PS) as well as to predict the effects of AS or PS in future PAH patients. Methods: The multi-scale lumped parameter CircAdapt model of the cardiovascular system was used to investigate the effects of AS and PS on cardiovascular hemodynamics and mechanics, as well as on oxygen saturation in moderate to severe PAH. The reference simulation, with cardiac output set to 2.1 l/min and mean systemic pressure to 61 mmHg, was used to create a compensated moderate PAH simulation with mPAP 50 mmHg. Thereupon we created a range of decompensated PAH simulations in which mPAP was stepwise increased from 50 to 80 mmHg. Then we simulated for each level of mPAP the acute effects of either PS or AS with connection diameters ranging between 0-16 mm. Results: For any mPAP level, the effect on shunt flow size is much larger for the PS than for AS. Whereas right ventricular pump work in PS is mainly dependent on mPAP, in AS it depends on both mPAP and the size of the defect. The effects on total cardiac pump work were similar for PS and AS. As expected, PS resulted in a drastic decrease of lower body oxygen saturation, whereas in AS both the upper and lower body oxygen saturation decreased, though not as drastically as in PS. Conclusion: Our simulations support the opinion that a PS can transfer suprasystemic PAH to an Eisenmenger physiology associated with a right-to-left shunt at the arterial level. Contrary to the current opinion that PS in PAH will decompress and unload the right ventricle, we show that while a PS does lead to a decrease in mPAP toward mean systemic arterial pressure, it does not unload the right ventricle because it mainly diverts flow from the pulmonary arterial system toward the lower body systemic arteries.

Pulmonary endothelial dysfunction due to a loss of pulsatile pulmonary blood flow is thought to be a major contributor in the development of increased pulmonary vascular resistance (PVR) in patients with a Fontan circulation. We sought to evaluate pulmonary endothelial dysfunction by vasodilator response to acetylcholine in children and adolescents with Fontan hemodynamics.Twenty-one Fontan patients with a median age of 10.7 years (range, 3.4-30.0 years) underwent invasive cardiac catheterization, including intra-arterial Doppler and pressure measurements in a segmental pulmonary artery. Pulmonary flow reserve (PFR) was quantified as the change of average peak velocity in response to acetylcholine infusion. Local PVR was assessed by the ratio of local pressure and blood flow velocity.Average peak velocity significantly increased from 16.4 ± 6.6 cm/s to 20.1 ± 6.4 cm/s (P = .002) resulting in a mean PFR of 1.28 ± 0.37. Local PVR dropped from 0.72 ± 0.32 mm Hg/cm/s to 0.57 ± 0.20 mm Hg/cm/s (n = 19; P = .01). A significant relationship was found between baseline local PVR and PFR (r = 0.73; P = .0006) as well as between PFR and the percent decrease in local PVR (r = 0.85; P .0001). In addition, percentage decrease in local PVR correlated with New York Heart Association functional class, whereas neither PFR nor local PVR correlated with global PVR.The assessment of PFR and local PVR may help to evaluate adverse pulmonary vascular remodeling in Fontan patients as an adjunct to the usual catheterization protocol, particularly given the difficulties in assessing global PVR in these patients. Future research is required to study whether impaired local pulmonary endothelial function may be associated with Fontan failure.

Objective Central pulmonary banding has been proposed as a novel alternative for the treatment of left ventricular dilated cardiomyopathy in children. We sought to investigate the effects of central pulmonary banding in an experimental model of doxorubicin-induced left ventricular dilated cardiomyopathy. Methods Four-month-old sheep (n = 28) were treated with intermittent intracoronary injections of doxorubicin (0.75 mg/kg/dose) into the left main coronary artery. A total dose of up to 2.15 mg/kg of doxorubicin was administered until signs of left ventricular dilation with functional impairment occurred by transthoracic echocardiography evaluation. Animals that survived were treated with surgical central pulmonary banding through a left anterior thoracotomy or sham surgery. Transthoracic echocardiography and pressure-volume loop measurements were used to compare left ventricular function preoperatively and 3 months later. Macroscopic and microscopic histologic examinations followed after hearts were harvested. Results Nine animals from the central pulmonary banding group and 8 animals from the sham group survived and were included in the final analysis. Both groups showed similar inflammation and fibrosis upon histologic examination consistent with the toxic myocardial effects of doxorubicin. There were no differences in the echocardiographic measurements before central pulmonary banding or sham operation. Baseline measurements before the central pulmonary banding/sham operation were considered as 100%. The central pulmonary banding group had better left ventricular ejection fraction (102.5% ± 21.6% vs 76.7% ± 11.7%, P = .01), with a tendency for smaller left ventricular end-diastolic (101.2% ± 7.4% vs 120.4% ± 10.8%, P = .18) and significantly smaller end-systolic (100.3% ± 12.9% vs 116.5 ± 9.6%, P = .02) diameter of the left ventricle in comparison with the sham animals at 3 months. The end-systolic volume (101.4% ± 31.6% vs 143.4% ± 28.6%, P = .02) was significantly lower in the central pulmonary banding group 3 months postoperatively. Fractional shortening in the long axis (118.5% ± 21.5% vs 85.2% ± 22.8%, P = .016) and short axis (122.5% ± 18% vs 80.9% ± 13.6%, P = .0005) revealed significantly higher values in the central pulmonary banding group. In the conductance catheter measurements, no significant differences were seen between the groups for the parameters of systolic and diastolic function. Conclusions Central pulmonary artery banding in the setting of experimental toxic left ventricular dilated cardiomyopathy improved left ventricular echocardiographic function and dimensions.

Right ventricular (RV) hypertrophy is regarded as the adaptation on chronic RV pressure load in pulmonary hypertension. As the RV Sokolow-Lyon index (RVSLI) is an electrocardiographic marker of RV hypertrophy, we hypothesized that RVSLI might be able to reflect RV pressure load. Therefore, the purpose of this study was to characterize the diagnostic impact of the RVSLI in children with idiopathic pulmonary arterial hypertension (IPAH) in order to assess disease severity and to evaluate its value for the prediction of worse outcome. Forty-two children (aged 3-17 years) with IPAH were included in this retrospective study. The follow-up after baseline examination was 59 ± 17 months. Receiver-operating characteristic (ROC) curves and Kaplan-Meier analysis were used to discriminate a cut-off value of RVSLI and to assess its predictive value regarding morbidity and mortality. In 12/42 patients (29%) severe cardiovascular events (defined as death, lung transplantation, or Potts shunt) were observed (time to event 20 ± 22 months). Patients with an event showed higher RVSLI values (3.6 ± 1.2 mV vs. 2.6 ± 1.6 mV; p 0.05). ROC analysis discriminated an RVSLI of 2.1 as the best cut-off value (area under the ROC curve: 0.79, sensitivity: 0.91, specificity: 0.70, p 0.05) to detect patients with high-risk PAH (mPAP/mSAP ratio 0.75). Relative risk for a severe event with an index 2.1 mV was 1.76 (95% CI 1.21-3.20). Relative risk for death with RVSLI 2.1 mV was 2.01 (95% CI 1.61-4.80). Our study demonstrates a strong relationship between RVSLI and disease severity in children with IPAH. An RVSLI 2.1 mV at the time of first diagnosis is a predictor for patients at risk for cardiac events. As an adjunct to the usual diagnostic assessment this parameter may therefore contribute to the initial prognostic estimation.

Objectives We report our experience with a transcatheter technique to bypass the lung and to thus improve single-ventricle preload and reduce venous congestion in Fontan patients. Background In the absence of a dedicated power source to serve the pulmonary circulation and a significantly elevated transpulmonary pressure gradient, fenestration of the Fontan circulation is an option to improve hemodynamics in patients by relieving excessive systemic venous pressure. Methods and Results From 2005 to 2011, 22 transcatheter fenestrations were performed without any major complications in 19 patients (median age 3.2 years, interquartile range (IQR) 2.7–3.7 years)) with failing Fontan circulation and exceeding systemic venous pressure. In 16 patients, the procedure was performed for acute postoperative failure 1–24 days after surgery. After perforation of the conduit and atrial wall by a Brockenbrough needle and gradual balloon dilation, premounted stents were expanded to create a diabolo configuration with flaring stent edges, leaving a slight but definitive central waist. The procedure resulted in regression of pleural effusions and a significant decrease in systemic venous pressure. Clinical improvement was observed in 16 of the 19 treated patients. Follow-up demonstrated sustained fenestration in 85% of treated patients for at least 24 months. Conclusion Transcatheter creation of a Fontan fenestration is a safe approach despite the anatomic gap between the extracardiac conduit cavity and the atrial wall. Stent implantation allows defining the diameter of the fenestration, reduces spontaneous occlusion, and ensures sustained clinical improvement. © 2015 Wiley Periodicals, Inc.

Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. In this Review, Latus et al. describe the latest medical, interventional, and surgical approaches to treating paediatric PAH. The authors highlight new PAH-specific drugs that are in development, and combined hybrid procedures that are delaying the need for lung transplantation. Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Improved understanding of the pathophysiological mechanisms of the underlying diseases has resulted in the development of effective, but not yet curative, therapies. Currently, drugs from three main pharmacological groups targeting specific aberrant pathways (endothelin, nitric oxide, and prostacyclin) and four routes of administration (inhaled, intravenous, oral, and subcutaneous) have been approved for adult patients with PAH. However, only a minority of these drugs has been officially approved for children, mainly because randomized controlled studies are limited by the small number of paediatric patients with PAH worldwide. In children with progressive, severe PAH and an inadequate response to drug therapy, advances in interventional and surgical approaches have provided promising new strategies to avoid right ventricular deterioration. These techniques can delay or even avoid the need for lung transplantation. In this Review, we present an update on developments in drug therapy for patients with PAH and highlight the current status of these treatments in children. We also describe the new surgical, interventional, and hybrid procedures, as well as their practical application in children with severe PAH.

ObjectiveDilated cardiomyopathy is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after establishing the diagnosis. New strategies are needed to improve the outcome in this high-risk patient population.Method and resultsWe present our experience in 38 patients below the age of three years, who were diagnosed with dilated cardiomyopathy and who were treated at our institution between 2006 and 2012. The treatment strategy involved institution of β-blockers and angiotensin-converting enzyme inhibitors as soon as feasible. In selected cases, pulmonary artery banding or intracoronary autologous bone marrow-derived cell therapy was performed. The median age at presentation was six months (range 1–26 months). The median follow-up age was 16 months (range 2–80 months). Kaplan–Meier analysis of survival after dilated cardiomyopathy diagnosis revealed a one-year survival of 97% and a five-year survival of 86%. The rate of freedom from death or heart transplantation was 82% at one year and 69% at five years. Surviving patients who were free of transplantation, at the follow-up at 25 months (3–80 months), showed a significant improvement in left ventricular ejection fraction (from 19±11 to 46±16%) and left ventricular end-diastolic diameter (z-score from 4.6±2.4 to 1.4±1.6). In addition, the levels of B-type natriuretic peptide improved significantly (from 3330±3840 to 171±825 pg/ml).ConclusionOur data suggest that the clinical approach described here may result in a markedly improved medium-term outcome in young children with dilated cardiomyopathy. Further studies are required to evaluate whether these approaches reduce end-points such as transplantation or death.

ObjectiveNorwood and hybrid procedure are two options available for initial palliation of patients with hypoplastic left heart syndrome (HLHS). Our study aimed to assess potential differences in right ventricular (RV) function and pulmonary artery dimensions using cardiac magnetic resonance (CMR) in survivors with HLHS.Methods42 Norwood (mean age 2.4±0.8) and 44 hybrid (mean age 2.0±1.0 years) patients were evaluated by CMR after stage II palliation prior to planned Fontan completion. Initial stage I Norwood procedure was performed using a modified Blalock-Taussig shunt, while the hybrid procedure consisted of bilateral pulmonary artery banding and arterial duct stenting. Need for reinterventions and subsequent outcomes were also assessed.ResultsNorwood patients had larger RV end-diastolic dimensions (91±23 vs 80±31 mL/m2, p=0.004) and lower heart rate (90±15 vs 102±13, p2/m2, p=0.02), and reintervention rate was significantly higher in the hybrid group whereas subsequent outcome did not differ significantly (p=0.24).ConclusionsNorwood and hybrid strategy were associated with equivalent and preserved global RV pump function while development of the pulmonary arteries and reintervention rate were superior using the Norwood approach. Impaired RV myocardial deformation as a potential marker of early RV dysfunction in the hybrid group may have a negative long-term impact in this population.

This review discusses the cardiovascular magnetic resonance (CMR) myocardial tissue characterization techniques and its applications with a focus on pediatric patients. Delayed enhancement CMR (DE-CMR) is well established to detect focal myocardial fibrosis in the clinical setting but has its limitation in detecting diffuse myocardial disease. Newer mapping techniques allow exact assessment of myocardial relaxation times and their changes in various cardiac pathologies. T1 mapping gives new insights in diffuse myocardial disease in pediatric patients with tetralogy of Fallot. T2 mapping seems to be superior to other CMR parameters for identifying myocarditis. Changes in myocardial T2* in thalassemia major can be detected in childhood suggesting that myocardial damage occurs early in life. Advanced CMR mapping techniques underlie a rapid development and enable a noninvasive characterization of the myocardium. Although data for young patients are limited, mapping techniques have the potential to become key imaging tools in pediatric patients.

Persistent or recurrent pulmonary arterial hypertension (PAH) following complete surgical repair of congenital heart disease (CHD) represents one of the largest group of PAH associated with CHD (PAH-CHD) in recent registry studies and seems to have a particularly poor prognosis. However, little is known about this fourth clinical subclass of PAH-CHD, especially in children. The purpose of this study was to assess specific characteristics of invasive hemodynamics of this disease in children, including acute vasodilator testing (AVT) and pulmonary endothelial function (PEF) and to compare to patients with idiopathic PAH (IPAH), who usually present with a similar fatal clinical course. Thirty-two children with PAH were included in the study, twelve of these patients had PAH-CHD subclass 4 (mean age 8.0 ± 3.4 years) and twenty children had IPAH (mean age 8.6 ± 4.4 years). Cardiac catheterization was performed in all children, including AVT and PEF. PEF was assessed by changes in pulmonary blood flow in response to acetylcholine (Ach) using Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. At baseline, the ratio of mean PA pressure to mean systemic arterial pressure (mPAP/mSAP) was comparably high in both groups (0.78 ± 0.32 vs. 0.80 ± 0.22), while the indexed pulmonary vascular resistance (PVRI) was significantly lower in the PAH-CHD group (12.6 ± 6.8 WUxm2) compared to IPAH patients (19.9 ± 10.6 WUxm2) (p = 0.04). Cardiac index was significantly higher in the PAH-CHD group (4.19 ± 1.09 l/min/m2 vs. 3.23 ± 0.76) (p = 0.017). However, AVT revealed a significantly larger maximum response (percentage of fall of PVR/SVR ratio during AVT) in the IPAH group (37 ± 22%) compared to the PAH-CHD group (13 ± 23%) (p = 0.017). PEF showed no significant difference between both patient groups (PFR 1.69 ± 0.71 vs. 1.73 ± 0.68) (p = 0.76). Our study demonstrates significant pulmonary vascular disease in children with persistent or recurrent PAH following complete surgical repair of CHD similar to IPAH patients. Although baseline measures appeared to be more favorable, pulmonary vasoreactivity was markedly impaired in PAH-CHD subclass 4, which may contribute to its negative impact on the long-term outcome of this patient group.