Radiomics-based aortic flow profile characterization with 4D phase-contrast MRI.

4D PC MRI of the aorta has become a routinely available examination, and a multitude of single parameters have been suggested for the quantitative assessment of relevant flow features for clinical studies and diagnosis. However, clinically applicable assessment of complex flow patterns is still challenging. We present a concept for applying radiomics for the quantitative characterization of flow patterns in the aorta. To this end, we derive cross-sectional scalar parameter maps related to parameters suggested in literature such as throughflow, flow direction, vorticity, and normalized helicity. Derived radiomics features are selected with regard to their inter-scanner and inter-observer reproducibility, as well as their performance in the differentiation of sex-, age- and disease-related flow properties. The reproducible features were tested on user-selected examples with respect to their suitability for characterizing flow profile types. In future work, such signatures could be applied for quantitative flow assessment in clinical studies or disease phenotyping.

The role of androgens in pressure overload myocardial hypertrophy.

Pressure overload hypertrophy of the left ventricle is a common result of many cardiovascular diseases. Androgens show anabolic effects in skeletal muscles, but also in myocardial hypertrophy. We carefully reviewed literature regarding possible effects of androgens on specific left ventricular hypertrophy in pressure overload conditions excluding volume overload conditions or generel sex differences.

Population-based reference values for 4D flow MRI derived aortic blood flow parameters.

Objective. This study assesses age-related differences of thoracic aorta blood flow profiles and provides age- and sex-specific reference values using 4D flow cardiovascular magnetic resonance (CMR) data.Approach. 126 volunteers (age 20-80 years, female 51%) underwent 4D flow CMR and 12 perpendicular analysis planes in the thoracic aorta were specified. For these planes the following parameters were evaluated: body surface area-adjusted aortic area (A'), normalized flow displacement (NFD), the degree of wall parallelism (WPD), the minimal relative cross-sectional area through which 80% of the volume flow passes (A80) and the angle between flow direction and centerline (α).Main results. Age-related differences in blood flow parameters were seen in the ascending aorta with higher values for NFD and angle and lower values for WPD and A80 in older subjects. All parameters describing blood flow patterns correlated with the cross-sectional area in the ascending aorta. No relevant sex-differences regarding blood flow profiles were found.Significance. These age- and sex-specific reference values for quantitative parameters describing blood flow within the aorta might help to study the clinical relevance of flow profiles in the future.

Disease- and sex-specific differences in patients with heart valve disease: a proteome study.

Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease- and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies.

Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement.

Animal studies show a pivotal role of dihydrotestosterone (DHT) in pressure overload-induced myocardial hypertrophy and dysfunction. The aim of our study was to evaluate the role of DHT levels and myocardial hypertrophy and myocardial protein expression in patients with severe aortic valve stenosis (AS). Forty-three patients [median age 68 (41-80) yr] with severe AS and indication for surgical aortic valve replacement (SAVR) were prospectively enrolled. Cardiac magnetic resonance imaging including analysis of left ventricular muscle mass (LVM), fibrosis and function, and laboratory tests including serum DHT levels were performed before and after SAVR. During SAVR, left ventricular (LV) biopsies were performed for proteomic profiling. Serum DHT levels correlated positively with indexed LVM (LVMi, R = 0.64, P = 0.0001) and fibrosis (R = 0.49, P = 0.0065) and inversely with LV function (R = -0.42, P = 0.005) in patients with severe AS. DHT levels were associated with higher abundance of the hypertrophy (moesin, R = 0.52, P = 0.0083)- and fibrosis (vimentin, R = 0.41, P = 0.039)-associated proteins from LV myocardial biopsies. Higher serum DHT levels preoperatively were associated with reduced LV function (ejection fraction, R = -0.34, P = 0.035; circulatory efficiency, R = -0.46, P = 0.012; and global longitudinal strain, R = 0.49, P = 0.01) and increased fibrosis (R = 0.55, P = 0.0022) after SAVR. Serum DHT levels were associated with adverse myocardial remodeling and higher abundance in hypertrophy- and fibrosis-associated proteins in patients with severe AS. DHT may be a target to prevent or attenuate adverse myocardial remodeling in patients with pressure overload due to AS.NEW & NOTEWORTHY Serum dihydrotestosterone (DHT) levels correlated positively with the degree of hypertrophy, fibrosis, and dysfunction from cardiac magnetic resonance imaging in female and male patients with aortic valve stenosis. Left ventricular proteome profiling had been performed in this patient cohort and an association between serum DHT levels and the abundance of the hypertrophy-associated protein moesin and the fibrosis-associated protein vimentin was found.

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.

Persisting and reoccurring cyanosis after Fontan operation is associated with increased late mortality.

OBJECTIVES: The Fontan operation aims at reducing cyanosis and cardiac volume overload in patients with complex univentricular heart malformations. However, persisting or reoccurring cyanosis is frequently observed. We sought to systematically determine the prevalence and clinical consequences of persisting and secondary cyanosis after Fontan operation. METHODS: A total of 331 Fontan patients, operated between 1984 and 2016 with a median postoperative follow-up of 7.9 (interquartile range 2.6-15.8) years, were studied retrospectively. Cyanosis was defined as transcutaneous oxygen saturation ≤93% at rest measured by pulse oximetry. Prevalence of cyanosis was analysed at 3 different time points (t1 = post-Fontan operation, t2 = post-Fontan cardiac catheterization, t3 = last follow-up) and the association of cyanosis with mortality was examined. RESULTS: Prevalence of cyanosis was 50% at t1 and 39% at t3. Fenestration was patent in 71% and 33% of all cyanotic patients at t1 and t3, respectively. In patients with clinical indication for catheterization (t2; n = 178/331), prevalence of cyanosis was 72%. At t2, patent fenestration (33%), veno-venous collaterals (24%) or both (32%) were present. Thirty-six (11%) patients died during follow-up. In a time-varying multivariable Cox regression analysis, cyanosis was the strongest predictor for late mortality (P < 0.001, hazard ratio 12.2, 95% confidence interval 3.7-40.5). CONCLUSIONS: Prevalence of cyanosis was considerable during long-term follow-up after Fontan operation and-as a surrogate parameter for unfavourable Fontan haemodynamics-is associated with increased late mortality. Accordingly, particular attention should be directed towards the persistence or reoccurrence of cyanosis during follow-up since it may indicate haemodynamic attrition and development of Fontan failure.

Wearable devices can predict the outcome of standardized 6-minute walk tests in heart disease.

Wrist-worn devices with heart rate monitoring have become increasingly popular. Although current guidelines advise to consider clinical symptoms and exercise tolerance during decision-making in heart disease, it remains unknown to which extent wearables can help to determine such functional capacity measures. In clinical settings, the 6-minute walk test has become a standardized diagnostic and prognostic marker. We aimed to explore, whether 6-minute walk distances can be predicted by wrist-worn devices in patients with different stages of mitral and aortic valve disease. A total of n = 107 sensor datasets with 1,019,748 min of recordings were analysed. Based on heart rate recordings and literature information, activity levels were determined and compared to results from a 6-minute walk test. The percentage of time spent in moderate activity was a predictor for the achievement of gender, age and body mass index-specific 6-minute walk distances (p < 0.001; R 2 = 0.48). The uncertainty of these predictions is demonstrated.

Fontan completion during winter season is not associated with higher mortality or morbidity in the early post-operative period.

OBJECTIVES: The aim of our study was to compare post-operative outcome after total cavopulmonary connection between patients operated during winter and summer season. METHODS: We retrospectively studied 211 patients who underwent extracardiac total cavopulmonary connection completion at our institution between 1995 and 2015 (median age 4 (1-42) years). Seventy (33%) patients were operated during winter (November to March) and 141 (67%) patients during summer season (April to October). RESULTS: Patients operated during winter and summer season showed no difference in early mortality (7% versus 5%, p = 0.52) and severe morbidity like need for early Fontan takedown (1% versus 1%, p = 0.99) and need for mechanical circulatory support (9% versus 4%, p = 0.12). The post-operative course and haemodynamic outcome were comparable between both groups of patients (ICU (4 versus 3 days, p = 0.44) and hospital stay (15 versus 14 days, p = 0.28), prolonged pleural effusions (36% versus 31%, p = 0.51), need for dialysis (16% versus 11%, p = 0.37), ascites (37% versus 33%, p = 0.52), supraventricular tachyarrhythmia (16% versus 13%, p = 0.56) and chylothorax (26% versus 16%, p = 0.12), change of antibiotic treatment (47% versus 36%, p = 0.06), prolonged inotropic support (24% versus 14%, p = 0.05), intubation time (15 versus 12 hours, p = 0.33), and incidence of fast-track extubation (11% versus 22%, p = 0.06). CONCLUSION: Outcomes after total cavopulmonary connection completion during winter and summer season were comparably related to mortality, severe morbidity, or longer hospital stay in the early post-operative period. These results suggest that total cavopulmonary connection completion during winter season is as safe as during summer season.

Impact of valve morphology, hypertension and age on aortic wall properties in patients with coarctation: a two-centre cross-sectional study.

OBJECTIVE: We aimed to investigate the combined effects of arterial hypertension, bicuspid aortic valve disease (BAVD) and age on the distensibility of the ascending and descending aortas in patients with aortic coarctation. DESIGN: Cross-sectional study. SETTING: The study was conducted at two university medical centres, located in Berlin and London. PARTICIPANTS: A total of 121 patients with aortic coarctation (ages 1-71 years) underwent cardiac MRI, echocardiography and blood pressure measurements. OUTCOME MEASURES: Cross-sectional diameters of the ascending and descending aortas were assessed to compute aortic area distensibility. Findings were compared with age-specific reference values. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology statement and reporting guidelines. RESULTS: Impaired distensibility (below fifth percentile) was seen in 37% of all patients with coarctation in the ascending aorta and in 43% in the descending aorta. BAVD (43%) and arterial hypertension (72%) were present across all ages. In patients >10 years distensibility impairment of the ascending aorta was predominantly associated with BAVD (OR 3.1, 95% CI 1.33 to 7.22, p=0.009). Distensibility impairment of the descending aorta was predominantly associated with arterial hypertension (OR 2.8, 95% CI 1.08 to 7.2, p=0.033) and was most pronounced in patients with uncontrolled hypertension despite antihypertensive treatment. CONCLUSION: From early adolescence on, both arterial hypertension and BAVD have a major impact on aortic distensibility. Their specific effects differ in strength and localisation (descending vs ascending aorta). Moreover, adequate blood pressure control is associated with improved distensibility. These findings could contribute to the understanding of cardiovascular complications and the management of patients with aortic coarctation.

Hemodynamic Modeling of Biological Aortic Valve Replacement Using Preoperative Data Only.

Objectives: Prediction of aortic hemodynamics after aortic valve replacement (AVR) could help optimize treatment planning and improve outcomes. This study aims to demonstrate an approach to predict postoperative maximum velocity, maximum pressure gradient, secondary flow degree (SFD), and normalized flow displacement (NFD) in patients receiving biological AVR. Methods: Virtual AVR was performed for 10 patients, who received actual AVR with a biological prosthesis. The virtual AVRs used only preoperative anatomical and 4D flow MRI data. Subsequently, computational fluid dynamics (CFD) simulations were performed and the abovementioned hemodynamic parameters compared between postoperative 4D flow MRI data and CFD results. Results: For maximum velocities and pressure gradients, postoperative 4D flow MRI data and CFD results were strongly correlated (R 2 = 0.75 and R 2 = 0.81) with low root mean square error (0.21 m/s and 3.8 mmHg). SFD and NFD were moderately and weakly correlated at R 2 = 0.44 and R 2 = 0.20, respectively. Flow visualization through streamlines indicates good qualitative agreement between 4D flow MRI data and CFD results in most cases. Conclusion: The approach presented here seems suitable to estimate postoperative maximum velocity and pressure gradient in patients receiving biological AVR, using only preoperative MRI data. The workflow can be performed in a reasonable time frame and offers a method to estimate postoperative valve prosthesis performance and to identify patients at risk of patient-prosthesis mismatch preoperatively. Novel parameters, such as SFD and NFD, appear to be more sensitive, and estimation seems harder. Further workflow optimization and validation of results seems warranted.

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.

Surrogates for myocardial power and power efficiency in patients with aortic valve disease.

We aimed to assess surrogate markers for left ventricular (LV) myocardial power and efficiency in patients with isolated aortic stenosis (AS) and combined stenosis/regurgitation (AS/AR). In AS (n = 59), AS/AR (n = 21) and controls (n = 14), surrogates for LV myocardial power and circulatory/external myocardial efficiency were obtained from cardiac MRI. Median surrogate LV myocardial power was increased in AS, 7.7 W/m2 (interquartile range 6.0-10.2; p = 0.010) and AS/AR, 10.8 W/m2 (8.9-13.4; p < 0.001) when compared to controls, 5.4 W/m2 (4.2-6.5), and was lower in AS than AS/AR (p < 0.001). Surrogate circulatory efficiency was decreased in AS, 8.6% (6.8-11.1; p < 0.001) and AS/AR, 5.4% (4.1-6.2; p < 0.001) when compared to controls, 11.8% (9.8-16.9). Surrogate external myocardial efficiency was higher in AS, 15.2% (11.9-18.6) than in AS/AR, 12.2% (10.1-14.2; p = 0.031) and was significantly lower compared to controls, 12.2% (10.7-18.1) in patients with reduced ejection fraction (EF), 9.8% (8.1-11.7; p = 0.025). In 16% of all cases, left ventricular mass/volume indices and EF were within normal ranges, wheras surrogate LV myocardial power was elevated and patients were symptomatic. Although influenced by pressure/volume load, the myocardium is additionally affected by remodelling processes. Surrogates for circulatory efficiency and LV myocardial power gradually reflect alterations in patients with AS and AS/AR, even when surrogate external myocardial efficiency, EF, mass and volume indices still remain compensated.

ADAPT-treated pericardium for aortic valve reconstruction in congenital heart disease: histological analysis of a series of human explants.

OBJECTIVES: Different types of patch materials are used for aortic valve repair in children with congenital aortic valve disease to avoid early valve replacement. CardioCel© (Admedus, Toowong, QLD, Australia) consists of bovine pericardium treated with the ADAPT method (Admedus' proprietary tissue engineering process). METHODS: Our goal was to describe tissue reactions in 12 explanted aortic valve leaflet specimens (augmented or replaced with CardioCel patch material) (11 explanted surgically, 1 autopsy). Explantation was performed during reoperation after aortic valve repair, necessitated by aortic valve stenosis in 5, aortic valve insufficiency in 2, combined aortic valve lesions in 3 patients and endocarditis in 1 patient. One patient died of sudden left heart failure 28 months after aortic valve repair. At the last documented follow-up of this patient at 22 months, he showed mild aortic valve stenosis and insufficiency. Implantation time (time between implantation and explantation) of CardioCel patches was a median of 25 (range 11-47) months. Explants were examined using a uniform protocol with methylmethacrylate and/or paraffin embedding after fixation in formalin. Besides standard histological staining, von Kossa (for identification of calcifications) and immunohistochemical stains were applied with antibodies specific for muscular, inflammatory and connective tissue component antigens. Findings regarding the extent of appositional growth on top of the patch consisting of fibroblasts and extracellular matrix components, calcification, and inflammation were rated using a 4-grade scale (G0 no/G1 few/G2 moderate/G3 massive). RESULTS: Superficial endothelialization was demonstrated in all patients by immunohistochemical analysis. Nine specimens showed mild inflammatory cell infiltration (G1) (G2: n = 3). Significant appositional growth on top of the patch due to addition of fibroblasts and extracellular matrix components, was seen in all specimens (G1: n = 1; G2: n = 7; G3: n = 4). Ten of 12 samples with implant times of 23 months or longer revealed calcifications (G1: n = 6; G2: n = 3; G3: n = 1). Two specimens with the shortest implant times (11 and 20 months) showed no calcifications (G0). Thrombus apposition with granulocyte infiltration was demonstrated in the specimen of the patient with endocarditis. CONCLUSIONS: In our cohort, all CardioCel patches used for aortic valve repair in patients with congenital heart disease demonstrated appositional growth of fibroblasts and extracellular matrix components, and calcification after an implant time of at least 23 months.

Surgical Aortic Valve Replacement: Are We Able to Improve Hemodynamic Outcome?

Aortic valve replacement (AVR) does not usually restore physiological flow profiles. Complex flow profiles are associated with aorta dilatation, ventricle remodeling, aneurysms, and development of atherosclerosis. All these affect long-term morbidity and often require reoperations. In this pilot study, we aim to investigate an ability to optimize the real surgical AVR procedure toward flow profile associated with healthy persons. Four cases of surgical AVR (two with biological and two with mechanical valve prosthesis) with available post-treatment cardiac magnetic resonance imaging (MRI), including four-dimensional flow MRI and showing abnormal complex post-treatment hemodynamics, were investigated. All cases feature complex hemodynamic outcomes associated with valve-jet eccentricity and strong secondary flow characterized by helical flow and recirculation regions. A commercial computational fluid dynamics solver was used to simulate peak systolic hemodynamics of the real post-treatment outcome using patient-specific MRI measured boundary conditions. Then, an attempt to optimize hemodynamic outcome by modifying valve size and orientation as well as ascending aorta size reduction was made. Pressure drop, wall shear stress, secondary flow degree, helicity, maximal velocity, and turbulent kinetic energy were evaluated to characterize the AVR hemodynamic outcome. The proposed optimization strategy was successful in three of four cases investigated. Although no single parameter was identified as the sole predictor for a successful flow optimization, downsizing of the ascending aorta in combination with the valve orientation was the most effective optimization approach. Simulations promise to become an effective tool to predict hemodynamic outcome. The translation of these tools requires, however, studies with a larger cohort of patients followed by a prospective clinical validation study.

Intracardiac 4D Flow MRI in Congenital Heart Disease: Recommendations on Behalf of the ISMRM Flow & Motion Study Group.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:677-681.