Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

BACKGROUND: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls. METHODS: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content. RESULTS: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832). CONCLUSION: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.

Virtual treatment planning in three patients with univentricular physiology using computational fluid dynamics-Pitfalls and strategies.

Background: Uneven hepatic venous blood flow distribution (HFD) to the pulmonary arteries is hypothesized to be responsible for the development of intrapulmonary arteriovenous malformations (PAVM) in patients with univentricular physiology. Thus, achieving uniform distribution of hepatic blood flow is considered favorable. However, no established method for the prediction of the post-interventional hemodynamics currently exists. Computational fluid dynamics (CFD) offers the possibility to quantify HFD in patient-specific anatomies before and after virtual treatment. In this study, we evaluated the potential benefit of CFD-assisted treatment planning. Materials and methods: Three patients with total cavopulmonary connection (TCPC) and PAVM underwent cardiovascular magnetic resonance imaging (CMR) and computed tomography imaging (CT). Based on this imaging data, the patient-specific anatomy was reconstructed. These patients were considered for surgery or catheter-based intervention aiming at hepatic blood flow re-routing. CFD simulations were then performed for the untreated state as well as for different surgical and interventional treatment options. These treatment options were applied as suggested by treating cardiologists and congenital heart surgeons with longstanding experience in interventional and surgical treatment of patients with univentricular physiology. HFD was quantified for all simulations to identify the most viable treatment decision regarding redistribution of hepatic blood flow. Results: For all three patients, the complex TCPC anatomy could be reconstructed. However, due to the presence of metallic stent implants, hybrid models generated from CT as well as CMR data were required. Numerical simulation of pre-interventional HFD agreed well with angiographic assessment and physiologic considerations. One treatment option resulting in improvement of HFD was identified for each patient. In one patient follow-up data after treatment was available. Here, the virtual treatment simulation and the CMR flow measurements differed by 15%. Conclusion: The combination of modern computational methods as well as imaging methods for assessment of patient-specific anatomy and flow might allow to optimize patient-specific therapy planning in patients with pronounced hepatic flow mismatch and PAVM. In this study, we demonstrate that these methods can also be applied in patients with complex univentricular physiology and extensive prior interventions. However, in those cases, hybrid approaches utilizing information of different image modalities may be required.

CARDIOKIN1: Computational Assessment of Myocardial Metabolic Capability in Healthy Controls and Patients With Valve Diseases.

BACKGROUND: Many heart diseases can result in reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between myocardial ATP production (MVATP) and cardiac workload is important for better understanding disease development and choice of nutritional or pharmacologic treatment strategies. Because there is no method for measuring MVATP in vivo, the use of physiology-based metabolic models in conjunction with protein abundance data is an attractive approach. METHOD: We developed a comprehensive kinetic model of cardiac energy metabolism (CARDIOKIN1) that recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts, and in vivo studies with humans. We used the model to assess the energy status of the left ventricle of healthy participants and patients with aortic stenosis and mitral valve insufficiency. Maximal enzyme activities were individually scaled by means of protein abundances in left ventricle tissue samples. The energy status of the left ventricle was quantified by the ATP consumption at rest (MVATP[rest]), at maximal workload (MVATP[max]), and by the myocardial ATP production reserve, representing the span between MVATP(rest) and MVATP(max). RESULTS: Compared with controls, in both groups of patients, MVATP(rest) was increased and MVATP(max) was decreased, resulting in a decreased myocardial ATP production reserve, although all patients had preserved ejection fraction. The variance of the energetic status was high, ranging from decreased to normal values. In both patient groups, the energetic status was tightly associated with mechanic energy demand. A decrease of MVATP(max) was associated with a decrease of the cardiac output, indicating that cardiac functionality and energetic performance of the ventricle are closely coupled. CONCLUSIONS: Our analysis suggests that the ATP-producing capacity of the left ventricle of patients with valvular dysfunction is generally diminished and correlates positively with mechanical energy demand and cardiac output. However, large differences exist in the energetic state of the myocardium even in patients with similar clinical or image-based markers of hypertrophy and pump function. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03172338 and NCT04068740.

Cardiovascular magnetic resonance findings in non-hospitalized paediatric patients after recovery from COVID-19.

AIMS: Our study aimed to investigate the cardiac involvement with sensitive tissue characterization in non-hospitalized children with coronavirus disease 2019 (COVID-19) infection using cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: We prospectively enrolled children who recovered from mildly symptomatic COVID-19 infection between November 2020 and January 2021. Patients underwent CMR at 1.5 T (Achieva, Philips Healthcare, Best, the Netherlands) including cine images, native T1 and T2 mapping. Healthy children and paediatric patients with biopsy-proven myocarditis served as control groups. We performed CMR in 18 children with a median (25th-75th percentile) age of 12 (10-15) years, 38 (24-47) days after positive PCR test, and compared them with 7 healthy controls [15 (10-19) years] and 9 patients with myocarditis [10 (4-16) years]. The COVID-19 patients reported no cardiac symptoms. None of the COVID-19 patients showed CMR findings consistent with a myocarditis. Three patients (17%) from the COVID-19 cohort presented with minimal pericardial effusion. CMR parameters of COVID-19 patients, including volumetric and strain values as well as T1 and T2 times, were not significantly different from healthy controls, but from myocarditis patients. These had significantly reduced left ventricular (LV) ejection fraction (P = 0.035), LV global longitudinal strain, and left atrial strain values as well as elevated native T1 values compared with COVID-19 patients (P < 0.001, respectively). CONCLUSIONS: There was no evidence of myocardial inflammation, fibrosis, or functional cardiac impairment in the studied cohort of children recently. CMR findings were comparable with those of healthy controls. Pericardial effusion suggests a mild pericarditis in a small subgroup. This is pointing to a minor clinical relevance of myocardial involvement in children after mildly symptomatic COVID-19 infections.

Z-score mapping for standardized analysis and reporting of cardiovascular magnetic resonance modified Look-Locker inversion recovery (MOLLI) T1 data: Normal behavior and validation in patients with amyloidosis.

BACKGROUND: T1 mapping using modified Look-Locker inversion recovery (MOLLI) provides quantitative information on myocardial tissue composition. T1 results differ between sites due to variations in hardware and software equipment, limiting the comparability of results. The aim was to test if Z-scores can be used to compare the results of MOLLI T1 mapping from different cardiovascular magnetic resonance (CMR) platforms. METHODS: First, healthy subjects (n = 15) underwent 11 combinations of native short-axis T1 mapping (four CMR systems from two manufacturers at 1.5 T and 3 T, three MOLLI schemes). Mean and standard deviation (SD) of septal myocardial T1 were derived for each combination. T1 maps were transformed into Z-score maps based on mean and SD values using a prototype post-processing module. Second, Z-score mapping was applied to a validation sample of patients with cardiac amyloidosis at 1.5 T (n = 25) or 3 T (n = 13). RESULTS: In conventional T1 analysis, results were confounded by variations in field strength, MOLLI scheme, and manufacturer-specific system characteristics. Z-score-based analysis yielded consistent results without significant differences between any two of the combinations in part 1 of the study. In the validation sample, Z-score mapping differentiated between patients with cardiac amyloidosis and healthy subjects with the same diagnostic accuracy as standard T1 analysis regardless of field strength. CONCLUSIONS: T1 analysis based on Z-score mapping provides consistent results without significant differences due to field strengths, CMR systems, or MOLLI variants, and detects cardiac amyloidosis with the same diagnostic accuracy as conventional T1 analysis. Z-score mapping provides a means to compare native T1 results acquired with MOLLI across different CMR platforms.

Abnormal aortic flow profiles persist after aortic valve replacement in the majority of patients with aortic valve disease: how model-based personalized therapy planning could improve results. A pilot study approach.

OBJECTIVES: Complex blood flow profiles in the aorta are known to contribute to vessel dilatation. We studied flow profiles in the aorta in patients with aortic valve disease before and after surgical aortic valve replacement (AVR). METHODS: Thirty-four patients with aortic valve disease underwent 4-dimensional velocity-encoded magnetic resonance imaging before and after AVR (biological valve = 27, mechanical valve = 7). Seven healthy volunteers served as controls. Eccentricity (ES) and complex flow scores (CFS) were determined from the degree of helicity, vorticity and eccentricity of flow profiles in the aorta. Model-based therapy planning was used in 4 cases to improve in silico postoperative flow profiles by personalized adjustment of size, rotation and angulation of the valve as well as aorta diameter. RESULTS: Patients with aortic valve disease showed more complex flow than controls [median ES 2.5 (interquartile range (IQR) 2.3-2.7) vs 1.0 (IQR 1.0-1.0), P < 0.001, median CFS 4.7 (IQR 4.3-4.8) vs 1.0 (IQR 1.0-2.0), P < 0.001]. After surgery, flow complexity in the total patient cohort was reduced, but remained significantly higher compared to controls [median ES 2.3 (IQR 1.9-2.3) vs 1.0 (IQR 1.0-1.0), P < 0.001, median CFS 3.8 (IQR 3.0-4.3) vs 1.0 (IQR 1.0-2.0), P < 0.001]. In patients after mechanical AVR, flow complexity fell substantially and showed no difference from controls [median ES 1.0 (IQR 1.0-2.3) vs 1.0 (IQR 1.0-1.0), P = 0.46, median CFS 1.0 (IQR 1.0-3.3) vs 1.0 (IQR 1.0-2.0), P = 0.71]. In all 4 selected cases (biological, n = 2; mechanical, n = 2), model-based therapy planning reduced in silico complexity of flow profiles compared to the existing post-surgical findings [median ES 1.7 (IQR 1.4-1.7) vs 2.3 (IQR 2.3-2.3); CFS 1.7 (IQR 1.4-2.5) vs 3.8 (IQR 3.3-4.3)]. CONCLUSIONS: Abnormal flow profiles in the aorta more frequently persist after surgical AVR. Model-based therapy planning might have the potential to optimize treatment for best possible individual outcome. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT03172338, 1 June 2017, retrospectively registered; NCT02591940, 30 October 2015, retrospectively registered.

Impact of predictive medicine on therapeutic decision making: a randomized controlled trial in congenital heart disease.

Computational modelling has made significant progress towards clinical application in recent years. In addition to providing detailed diagnostic data, these methods have the potential to simulate patient-specific interventions and to predict their outcome. Our objective was to evaluate to which extent patient-specific modelling influences treatment decisions in coarctation of the aorta (CoA), a common congenital heart disease. We selected three cases with CoA, two of which had borderline indications for intervention according to current clinical guidelines. The third case was not indicated for intervention according to guidelines. For each case, we generated two separate datasets. First dataset included conventional diagnostic parameters (echocardiography and magnetic resonance imaging). In the second, we added modelled parameters (pressure fields). For the two cases with borderline indications for intervention, the second dataset also included pressure fields after virtual stenting simulations. All parameters were computed by modelling methods that were previously validated. In an online-administered, invitation-only survey, we randomized 178 paediatric cardiologists to view either conventional (control) or add-on modelling (experimental) datasets. Primary endpoint was the proportion of participants recommending different therapeutic options: (1) surgery or catheter lab (collectively, "intervention") or (2) no intervention (follow-up with or without medication). Availability of data from computational predictive modelling influenced therapeutic decision making in two of three cases. There was a statistically significant association between group assignment and the recommendation of an intervention for one borderline case and one non-borderline case: 94.3% vs. 72.2% (RR: 1.31, 95% CI: 1.14-1.50, p = 0.00) and 18.8% vs. 5.1% (RR: 3.09, 95% CI: 1.17-8.18, p = 0.01) of participants in the experimental and control groups respectively recommended an intervention. For the remaining case, there was no difference between the experimental and control group and the majority of participants recommended intervention. In sub-group analyses, findings were not affected by the experience level of participating cardiologists. Despite existing clinical guidelines, the therapy recommendations of the participating physicians were heterogeneous. Validated patient-specific computational modelling has the potential to influence treatment decisions. Future studies in broader areas are needed to evaluate whether differences in decisions result in improved outcomes (Trial Registration: NCT02700737).

User-dependent variability in mitral valve segmentation and its impact on CFD-computed hemodynamic parameters.

PURPOSE: While novel tools for segmentation of the mitral valve are often based on automatic image processing, they mostly require manual interaction by a proficient user. Those segmentations are essential for numerical support of mitral valve treatment using computational fluid dynamics, where the reconstructed geometry is incorporated into a simulation domain. To quantify the uncertainty and reliability of hemodynamic simulations, it is crucial to examine the influence of user-dependent variability in valve segmentation. METHODS: Previously, the inter-user variability of landmarks in mitral valve segmentation was investigated. Here, the inter-user variability of geometric parameters of the mitral valve, projected orifice area (OA) and projected annulus area (AA), is investigated for 10 mitral valve geometries, each segmented by three users. Furthermore, the propagation of those variations into numerically calculated hemodynamics, i.e., the blood flow velocity, was investigated. RESULTS: Among the three geometric valve parameters, AA was least user-dependent. Almost all deviations to the mean were below 10%. Larger variations were observed for OA. Variations observed for the numerically calculated hemodynamics were in the same order of magnitude as those of geometric parameters. No correlation between variation of geometric parameters and variation of calculated hemodynamic parameters was found. CONCLUSION: Errors introduced due to the user-dependency were of the same size as the variations of calculated hemodynamics. The variation was thereby of the same scale as deviations in clinical measurements of blood flow velocity using Doppler echocardiography. Since no correlation between geometric and hemodynamic uncertainty was found, further investigation of the complex relationship between anatomy, leaflet shape and flow is necessary.

Machine learning for real-time prediction of complications in critical care: a retrospective study.

BACKGROUND: The large amount of clinical signals in intensive care units can easily overwhelm health-care personnel and can lead to treatment delays, suboptimal care, or clinical errors. The aim of this study was to apply deep machine learning methods to predict severe complications during critical care in real time after cardiothoracic surgery. METHODS: We used deep learning methods (recurrent neural networks) to predict several severe complications (mortality, renal failure with a need for renal replacement therapy, and postoperative bleeding leading to operative revision) in post cardiosurgical care in real time. Adult patients who underwent major open heart surgery from Jan 1, 2000, to Dec 31, 2016, in a German tertiary care centre for cardiovascular diseases formed the main derivation dataset. We measured the accuracy and timeliness of the deep learning model's forecasts and compared predictive quality to that of established standard-of-care clinical reference tools (clinical rule for postoperative bleeding, Simplified Acute Physiology Score II for mortality, and the Kidney Disease: Improving Global Outcomes staging criteria for acute renal failure) using positive predictive value (PPV), negative predictive value, sensitivity, specificity, area under the curve (AUC), and the F1 measure (which computes a harmonic mean of sensitivity and PPV). Results were externally retrospectively validated with 5898 cases from the published MIMIC-III dataset. FINDINGS: Of 47 559 intensive care admissions (corresponding to 42 007 patients), we included 11 492 (corresponding to 9269 patients). The deep learning models yielded accurate predictions with the following PPV and sensitivity scores: PPV 0·90 and sensitivity 0·85 for mortality, 0·87 and 0·94 for renal failure, and 0·84 and 0·74 for bleeding. The predictions significantly outperformed the standard clinical reference tools, improving the absolute complication prediction AUC by 0·29 (95% CI 0·23-0·35) for bleeding, by 0·24 (0·19-0·29) for mortality, and by 0·24 (0·13-0·35) for renal failure (p<0·0001 for all three analyses). The deep learning methods showed accurate predictions immediately after patient admission to the intensive care unit. We also observed an increase in performance in our validation cohort when the machine learning approach was tested against clinical reference tools, with absolute improvements in AUC of 0·09 (95% CI 0·03-0·15; p=0·0026) for bleeding, of 0·18 (0·07-0·29; p=0·0013) for mortality, and of 0·25 (0·18-0·32; p<0·0001) for renal failure. INTERPRETATION: The observed improvements in prediction for all three investigated clinical outcomes have the potential to improve critical care. These findings are noteworthy in that they use routinely collected clinical data exclusively, without the need for any manual processing. The deep machine learning method showed AUC scores that significantly surpass those of clinical reference tools, especially soon after admission. Taken together, these properties are encouraging for prospective deployment in critical care settings to direct the staff's attention towards patients who are most at risk. FUNDING: No specific funding.

Extraction of open-state mitral valve geometry from CT volumes.

PURPOSE: The importance of mitral valve therapies is rising due to an aging population. Visualization and quantification of the valve anatomy from image acquisitions is an essential component of surgical and interventional planning. The segmentation of the mitral valve from computed tomography (CT) acquisitions is challenging due to high variation in appearance and visibility across subjects. We present a novel semi-automatic approach to segment the open-state valve in 3D CT volumes that combines user-defined landmarks to an initial valve model which is automatically adapted to the image information, even if the image data provide only partial visibility of the valve. METHODS: Context information and automatic view initialization are derived from segmentation of the left heart lumina, which incorporates topological, shape and regional information. The valve model is initialized with user-defined landmarks in views generated from the context segmentation and then adapted to the image data in an active surface approach guided by landmarks derived from sheetness analysis. The resulting model is refined by user landmarks. RESULTS: For evaluation, three clinicians segmented the open valve in 10 CT volumes of patients with mitral valve insufficiency. Despite notable differences in landmark definition, the resulting valve meshes were overall similar in appearance, with a mean surface distance of [Formula: see text] mm. Each volume could be segmented in 5-22 min. CONCLUSIONS: Our approach enables an expert user to easily segment the open mitral valve in CT data, even when image noise or low contrast limits the visibility of the valve.

Development of a modeling pipeline for the prediction of hemodynamic outcome after virtual mitral valve repair using image-based CFD.

PURPOSE: Severe mitral valve regurgitation can either be treated by a replacement or a repair of the valve. The latter is recommended due to lower perioperative mortality and better long-term survival. On the other hand, recurrence rates after mitral valve repair are high compared to those after replacements and the repair intervention can cause induced mitral valve stenosis. So far, there are no methods to predict the hemodynamic outcome of a chosen treatment or to compare different treatment options in advance. To overcome this, diastolic mitral valve hemodynamics are simulated using computational fluid dynamics after different virtual treatments of the valve. METHODS: The left ventricular geometry of one patient was reconstructed using trans-esophageal echocardiography and computed tomography data. Pre-op hemodynamics are simulated using a referenced wall model to avoid expansive modeling of wall motion. Subsequently, the flow structures are compared to in vivo measurements. After manipulating the patient-specific geometry in order to mimic a restrictive mitral annuloplasty as well as a MitraClip intervention, hemodynamics results are calculated. RESULTS: Good agreements exist between calculated pre-op hemodynamics and in vivo measurements. The virtual annuloplasty did not result in any remarkable change of hemodynamics. Neither the pressure drop nor the velocity field showed strong differences. In contrast, the virtual MitraClip intervention led to a complete change in blood flow structures as well as an elevated pressure drop across the valve. CONCLUSION: The presented approach allows fast simulation of the diastolic hemodynamic situation before and after treatment of a mitral valve insufficiency. However, this approach is limited to the early diastolic phase of the cardiac cycle and needs to be validated using a larger sample size.

Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

BACKGROUND: We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. METHODS: A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. RESULTS: In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. CONCLUSIONS: Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

Avoidable costs of stenting for aortic coarctation in the United Kingdom: an economic model.

BACKGROUND: Undesirable outcomes in health care are associated with patient harm and substantial excess costs. Coarctation of the aorta (CoA), one of the most common congenital heart diseases, can be repaired with stenting but requires monitoring and subsequent interventions to detect and treat disease recurrence and aortic wall injuries. Avoidable costs associated with stenting in patients with CoA are unknown. METHODS: We developed an economic model to calculate potentially avoidable costs in stenting treatment of CoA in the United Kingdom over 5 years. We calculated baseline costs for the intervention and potentially avoidable complications and follow-up interventions and compared these to the costs in hypothetical scenarios with improved treatment effectiveness and complication rates. RESULTS: Baseline costs were £16 688 ($25 182) per patient. Avoidable costs ranged from £137 ($207) per patient in a scenario assuming a 10% reduction in aortic wall injuries and reinterventions at follow-up, to £1627 ($2455) in a Best-case scenario with 100% treatment success and no complications. Overall costs in the Best-case scenario were 90.2% of overall costs at Baseline. Reintervention rate at follow-up was identified as most influential lever for overall costs. Probabilistic sensitivity analysis showed a considerable degree of uncertainty for avoidable costs with widely overlapping 95% confidence intervals. CONCLUSIONS: Significant improvements in the treatment effectiveness and reductions in complication rates are required to realize discernible cost savings. Up to 10% of total baseline costs could be avoided in the best-case scenario. This highlights the need to pursue patient-specific treatment approaches which promise optimal outcomes.

Bicuspid aortic valve disease: systematic review and meta-analysis of surgical aortic valve repair.

Aortic valve repair is still emerging, and its role in the treatment of bicuspid aortic valve disease (BAVD) is not yet fully understood. Our objective is to synthesise available evidence on outcomes after surgical aortic valve repair in patients with BAVD. We conducted a systematic review of clinical studies using prespecified methods for searching, identifying and selecting eligible studies in 4 databases, and synthesising results (PROSPERO 2014:CRD42014014415). 2 researchers independently reviewed full-text articles and extracted data. The results of included studies were quantitatively synthesised in frequentist meta-analyses. We included 11 aortic valve repair studies or study arms with a total of 2010 participants. Pooled estimates for the proportion of patients surviving at 30 days, 1 year, 5 years and 10 years were 0.995 (95% CI 0.991 to 0.995), 0.994 (0.989 to 0.999), 0.945 (0.898 to 0.993) and 0.912 (0.845 to 0.979), respectively. The pooled proportion of late deaths from valve-related causes was 0.008 (0.000 to 0.019) at a mean follow-up of 3.5 years. Proportion of patients with valve-related reinterventions was 0.075 (0.037 to 0.113) at a mean follow-up of 3.9 years, and the linearised reintervention rate was 1.3 (0.7 to 1.9) per 100 patient-years. Outcome reporting was insufficient to pool the results for a number of predefined outcomes. In conclusion, existing evidence on aortic valve repair in BAVD is limited to mostly small case series, case-control and small retrospective cohort studies. Despite the low quality, available evidence suggests favourable survival outcomes after aortic valve repair in selected patients with BAVD. Valve-related reinterventions at follow-up are common in all patients undergoing repair surgery.

Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

UNLABELLED: : The European Paediatric Pulmonary Vascular Disease (PVD) Network is a registered, non-profit organisation that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of paediatric pulmonary hypertensive vascular disease, including specific forms such as pulmonary arterial hypertension (PAH)-congenital heart disease, pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, persistent PH of the newborn, and related cardiac dysfunction. METHODS: The writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2015) and held five face-to-face meetings with votings. Clinical trials, guidelines, and reviews limited to paediatric data were searched using the terms 'pulmonary hypertension' and 5-10 other keywords, as outlined in the other nine articles of this special issue. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on paediatric data only, or on adult studies that included >10% children. RESULTS: A total of 9 original consensus articles with graded recommendations (COR/LOE) were developed, and are summarised here. The topics included diagnosis/monitoring, genetics/biomarker, cardiac catheterisation, echocardiography, cardiac magnetic resonance/chest CT, associated forms of PH, intensive care unit/ventricular assist device/lung transplantation, and treatment of paediatric PAH. CONCLUSIONS: The multipaper expert consensus statement of the European Paediatric PVD Network provides a specific, comprehensive, detailed but practical framework for the optimal clinical care of children with PH.

Myocardial T1 maps reflect histological findings in acute and chronic stages of myocarditis in a rat model.

BACKGROUND: Cardiovascular magnetic resonance offers both diagnostic and prognostic information in myocarditis. Using an established animal model of myocarditis, the aim of this study was to measure myocardial T1 before the onset, in the acute and in the chronic phases of the disease and to compare its course with histological and immunohistochemistry findings. METHODS: Male young Lewis rats were immunized with 0.25 mg porcine myocardial myosin into the rear footpads on day 0. Native and contrast-enhanced ECG-triggered cardiac MRI examinations were performed before immunization on day 0 and on days 14, 21 and 35. Left ventricular function, pre- and post- contrast T1 parameters and LGE images were assessed using Small animal look-locker inversion recovery (SALLI). For each of the indicated time points a minimum of 4 rats were randomly sacrificed for pathological investigations including conventional histology (HE and Sirius-Red staining) and immunohistochemistry (CD 68) investigations. RESULTS: All immunized rats developed myocarditis (morbidity 100%). Histologically we observed increased wall thickness with biventricular macrophage-rich mixed inflammatory infiltrates. All rats with a histologically severe myocarditis showed increased native T1 and decreased post-contrast T1 of the myocardium. CONCLUSIONS: The assessment of native T1 and post-contrast T1 allows accurate differentiation between healthy myocardium and myocardium with inflammation and also between the acute and chronic phases of the disease.

Interactive virtual stent planning for the treatment of coarctation of the aorta.

PURPOSE: The coarctation of the aorta (CoA), a local narrowing of the aortic arch, accounts for 7 % of all congenital heart defects. Stenting is a recommended therapy to reduce the pressure gradient. This procedure is associated with complications such as the development of adverse flow conditions. A computer-aided treatment planning based on flow simulations can help to predict possible complications. The virtual stent planning is an important, intermediate step in the treatment planning pipeline. We present a novel approach that automatically suggests a stent setup and provides a set of intuitive parameters that allow for an interactive adaption of the suggested stent placement and induced deformation. METHODS: A high-quality mesh and a centerline are automatically generated. The stent-induced deformation is realized through a deformation of the centerline and a vertex displacement with respect to the deformed centerline and additional stent parameters. The parameterization is automatically derived from the underlying data and can be optionally altered through a condensed set of clinically sound parameters. RESULTS: The automatic deformation can be generated in about 25 s on a consumer system. The interactive adaption can be performed in real time. Compared with manual expert reconstructions of the stented vessel section, the mean difference of vessel path and diameter is below 1 mm. CONCLUSION: Our approach enables a medical user to easily generate a plausibly deformed vessel mesh which is necessary as input for a simulation-based treatment planning of CoA.

Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society.

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Hemodynamic and energetic aspects of the left ventricle in patients with mitral regurgitation before and after mitral valve surgery.

BACKGROUND: The role of intracardiac blood flow behavior within the context of manifestation and interventional success in patients with mitral regurgitation is unknown to date. The present study aims to assess left ventricular blood flow behavior characterized by kinetic energy (KE) in patients with mitral regurgitation before and after mitral valve surgery. METHODS: Patients with mitral regurgitation (mean age 56 ± 9 years) and the necessity for mitral valve repair (n = 6) or biological valve replacement (n = 4) received cardiac magnetic resonance before and after surgery and were compared with a group of healthy volunteers (n = 7; mean age 27 ± 7 years). Volumetric data and KE of the left ventricle were obtained for all subjects. KE normalized and nonnormalized to volume was calculated from four-dimensional flow magnetic resonance imaging. Mean KE and KE peaks (systolic, early-diastolic and late diastolic), and end-systolic phase duration were considered. RESULTS: End-diastolic, end-systolic and stroke volume were significantly higher in patients with mitral regurgitation than in healthy volunteers (P = 0.00, 0.01, and 0.00, respectively) and decreased significantly after surgery (P = 0.00, 0.01, and 0.00, respectively). A significant postoperative decrease of mean KE, systolic and early-diastolic KE peaks was observed (P = 0.01, 0.02, and 0.01, respectively). Late-diastolic KE peak remained high in postoperative patients (P = 0.58). CONCLUSION: Intracardiac blood flow as characterized by measurements of KE is altered in patients with mitral regurgitation. Physiological flow conditions appear to not fully be restored with mitral valve surgery.