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.

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.

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.

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.

Hemodynamic Evaluation of a Biological and Mechanical Aortic Valve Prosthesis Using Patient-Specific MRI-Based CFD.

Modeling different treatment options before a procedure is performed is a promising approach for surgical decision making and patient care in heart valve disease. This study investigated the hemodynamic impact of different prostheses through patient-specific MRI-based CFD simulations. Ten time-resolved MRI data sets with and without velocity encoding were obtained to reconstruct the aorta and set hemodynamic boundary conditions for simulations. Aortic hemodynamics after virtual valve replacement with a biological and mechanical valve prosthesis were investigated. Wall shear stress (WSS), secondary flow degree (SFD), transvalvular pressure drop (TPD), turbulent kinetic energy (TKE), and normalized flow displacement (NFD) were evaluated to characterize valve-induced hemodynamics. The biological prostheses induced significantly higher WSS (medians: 9.3 vs. 8.6 Pa, P = 0.027) and SFD (means: 0.78 vs. 0.49, P = 0.002) in the ascending aorta, TPD (medians: 11.4 vs. 2.7 mm Hg, P = 0.002), TKE (means: 400 vs. 283 cm2 /s2 , P = 0.037), and NFD (means: 0.0994 vs. 0.0607, P = 0.020) than the mechanical prostheses. The differences between the prosthesis types showed great inter-patient variability, however. Given this variability, a patient-specific evaluation is warranted. In conclusion, MRI-based CFD offers an opportunity to assess the interactions between prosthesis and patient-specific boundary conditions, which may help in optimizing surgical decision making and providing additional guidance to clinicians.

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.

Evaluation of Intravenous Acetaminophen on Length of Stay in Abdominal Surgery Patients.

Purpose: The objective of this study is to evaluate the effect of intravenous acetaminophen on length of stay (LOS) in abdominal surgery patients. Methods: This retrospective, cohort chart review evaluated patients who underwent colon resection or pancreaticoduodenectomy between January 1, 2010 and August 31, 2013. The primary outcome is postoperative LOS. Secondary outcomes include opioid use, pain scores, and naloxone or laxative use. Patients who received intravenous acetaminophen were compared to patients who did not. Results: A total of 329 patients were included, with 269 in the non-acetaminophen group compared to 60 patients in the acetaminophen group. There was no difference in postoperative LOS (9.2 s vs 9.1 days; P = .90). Postoperative LOS was also similar when controlling for surgery type. The acetaminophen group had reduced opioid consumption in the first 24 hours postoperatively (P = .02). However, pain scores were higher in the acetaminophen group, both in the first 24 hours (P = .007) and throughout the hospital stay (P < .001). Other clinical outcomes were similar between groups. Conclusion: Intravenous acetaminophen was not associated with a decreased postoperative LOS at our institution.

Flow-sensitive four-dimensional velocity-encoded magnetic resonance imaging reveals abnormal blood flow patterns in the aorta and pulmonary trunk of patients with transposition.

BACKGROUND AND OBJECTIVES: Flow profiles are important determinants of fluid-vessel wall interactions. The aim of this study was to assess blood flow profiles in the aorta and pulmonary trunk in patients with transposition and different ventriculoarterial connection, and hence different mechanics of the coherent pump. METHODS: In all, 29 patients with operated transposition--concordant atrioventricular and discordant ventriculoarterial connection, and no other cardiac malformation--and eight healthy volunteers were assessed with cardiac magnetic resonance imaging: n = 17 patients after atrial redirection, with a morphologic right ventricle acting as systemic pump and a morphologic left ventricle connected to the pulmonary trunk, and n = 12 patients after the arterial switch procedure, with physiologic ventriculoarterial connections. Flow-sensitive four-dimensional velocity-encoded magnetic resonance imaging was used to analyse systolic flow patterns in the aorta and pulmonary trunk, relating to helical flow and vortex formation. RESULTS: In the aorta, overall helicity was present in healthy volunteers, but it was absent in all patients independent on the operation technique. Partial helices were observed in the ascending aorta of 58% of patients after arterial switch. In the pulmonary trunk, mostly parallel flow was seen in healthy volunteers and in patients after arterial switch, whereas vortex formation was present in 88% of patients after atrial redirection. CONCLUSION: Blood flow patterns differ substantially between the groups. In addition to varying mechanics of the coherent pumping ventricles, the absent overall helicity in all patients might be explained by the missing looping of the aorta in transposition.

Caval blood flow distribution in patients with Fontan circulation: quantification by using particle traces from 4D flow MR imaging.

PURPOSE: To validate the use of particle traces derived from four-dimensional (4D) flow magnetic resonance (MR) imaging to quantify in vivo the caval flow contribution to the pulmonary arteries (PAs) in patients who had been treated with the Fontan procedure. MATERIALS AND METHODS: The institutional review boards approved this study, and informed consent was obtained. Twelve healthy volunteers and 10 patients with Fontan circulation were evaluated. The particle trace method consists of creating a region of interest (ROI) on a blood vessel, which is used to emit particles with a temporal resolution of approximately 40 msec. The flow distribution, as a percentage, is then estimated by counting the particles arriving to different ROIs. To validate this method, two independent observers used particle traces to calculate the flow contribution of the PA to its branches in volunteers and compared it with the contribution estimated by measuring net forward flow volume (reference method). After the method was validated, caval flow contributions were quantified in patients. Statistical analysis was performed with nonparametric tests and Bland-Altman plots. P < .05 was considered to indicate a significant difference. RESULTS: Estimation of flow contributions by using particle traces was equivalent to estimation by using the reference method. Mean flow contribution of the PA to the right PA in volunteers was 54% ± 3 (standard deviation) with the reference method versus 54% ± 3 with the particle trace method for observer 1 (P = .4) and 54% ± 4 versus 54% ± 4 for observer 2 (P = .6). In patients with Fontan circulation, 87% ± 13 of the superior vena cava blood flowed to the right PA (range, 63%-100%), whereas 55% ± 19 of the inferior vena cava blood flowed to the left PA (range, 22%-82%). CONCLUSION: Particle traces derived from 4D flow MR imaging enable in vivo quantification of the caval flow distribution to the PAs in patients with Fontan circulation. This method might allow the identification of patients at risk of developing complications secondary to uneven flow distribution. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120778/-/DC1.

Four-dimensional velocity-encoded magnetic resonance imaging improves blood flow quantification in patients with complex accelerated flow.

PURPOSE: To evaluate the use of four-dimensional (4D) velocity-encoded magnetic resonance imaging (VEC MRI) for blood flow quantification in patients with semilunar valve stenosis and complex accelerated flow. MATERIALS AND METHODS: Peak velocities (Vmax) and stroke volumes (SV) were quantified by 2D and 4D VEC MRI in volunteers (n = 7) and patients with semilunar valve stenosis (n = 18). Measurements were performed above the aortic and pulmonary valve with both techniques and, additionally, at multiple predefined planes in the ascending aorta and in the pulmonary trunk within the 4D dataset. In patients, 4D VEC MRI streamline analysis identified flow patterns and regions of highest flow velocity (4D(max-targeted)) for further measurements and Vmax was also measured by Doppler-echocardiography. RESULTS: In patients, 4D VEC MRI showed higher Vmax than 2D VEC MRI (2.7 ± 0.6 m/s vs. 2.4 ± 0.5 m/s, P < 0.03) and was more comparable to Doppler-echocardiography (2.8 ± 0.7 m/s). 4D(max-targeted) revealed highest Vmax values (3.1 ± 0.6 m/s). SV measurements showed significant differences between different anatomical levels in the ascending aorta in patients with complex accelerated flow, whereas differences in volunteers with laminar flow patterns were negligible (P = 0.004). CONCLUSION: 4D VEC MRI improves MRI-derived blood flow quantification in patients with semilunar valve stenosis and complex accelerated flow.

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.

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.

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.

Systemic-to-pulmonary collateral flow in patients with palliated univentricular heart physiology: measurement using cardiovascular magnetic resonance 4D velocity acquisition.

BACKGROUND: Systemic-to-pulmonary collateral flow (SPCF) may constitute a risk factor for increased morbidity and mortality in patients with single-ventricle physiology (SV). However, clinical research is limited by the complexity of multi-vessel two-dimensional (2D) cardiovascular magnetic resonance (CMR) flow measurements. We sought to validate four-dimensional (4D) velocity acquisition sequence for concise quantification of SPCF and flow distribution in patients with SV. METHODS: 29 patients with SV physiology prospectively underwent CMR (1.5 T) (n = 14 bidirectional cavopulmonary connection [BCPC], age 2.9 ± 1.3 years; and n = 15 Fontan, 14.4 ± 5.9 years) and 20 healthy volunteers (age, 28.7 ± 13.1 years) served as controls. A single whole-heart 4D velocity acquisition and five 2D flow acquisitions were performed in the aorta, superior/inferior caval veins, right/left pulmonary arteries to serve as gold-standard. The five 2D velocity acquisition measurements were compared with 4D velocity acquisition for validation of individual vessel flow quantification and time efficiency. The SPCF was calculated by evaluating the disparity between systemic (aortic minus caval vein flows) and pulmonary flows (arterial and venour return). The pulmonary right to left and the systemic lower to upper body flow distribution were also calculated. RESULTS: The comparison between 4D velocity and 2D flow acquisitions showed good Bland-Altman agreement for all individual vessels (mean bias, 0.05 ± 0.24 l/min/m2), calculated SPCF (-0.02 ± 0.18 l/min/m2) and significantly shorter 4D velocity acquisition-time (12:34 min/17:28 min,p < 0.01). 4D velocity acquisition in patients versus controls revealed (1) good agreement between systemic versus pulmonary estimator for SPFC; (2) significant SPCF in patients (BCPC 0.79 ± 0.45 l/min/m2; Fontan 0.62 ± 0.82 l/min/m2) and not in controls (0.01 + 0.16 l/min/m2), (3) inverse relation of right/left pulmonary artery perfusion and right/left SPCF (Pearson = -0.47,p = 0.01) and (4) upper to lower body flow distribution trend related to the weight (r = 0.742, p < 0.001) similar to the controls. CONCLUSIONS: 4D velocity acquisition is reliable, operator-independent and more time-efficient than 2D flow acquisition to quantify SPCF. There is considerable SPCF in BCPC and Fontan patients. SPCF was more pronounced towards the respective lung with less pulmonary arterial flow suggesting more collateral flow where less anterograde branch pulmonary artery perfusion.

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.

Small animal Look-Locker inversion recovery (SALLI) for simultaneous generation of cardiac T1 maps and cine and inversion recovery-prepared images at high heart rates: initial experience.

PURPOSE: To develop a single magnetic resonance (MR) imaging approach for comprehensive assessment of cardiac function and tissue properties in small animals with high heart rates. MATERIALS AND METHODS: All animal studies were approved by the local animal care committee. Small animal Look-Locker inversion recovery (SALLI) was implemented on a clinical 3.0-T MR unit equipped with a 70-mm solenoid coil. SALLI combines a segmented, electrocardiographically gated, inversion recovery-prepared Look-Locker-type pulse sequence with a multimodal reconstruction framework. Temporal undersampling and radial nonbalanced steady-state free precession enabled acceleration of data acquisition and reduction of motion artifacts, respectively. Nine agarose gel phantoms were used to investigate different sequence settings. For in vivo studies, 10 Sprague-Dawley rats were evaluated to establish normal T1 values before and after injection of gadopentetate dimeglumine. Seven rats with surgically induced acute myocardial infarction were examined to test the feasibility of detecting myocardial injury. In vitro T1 behavior was studied with linear regression analysis, and in vivo T1 differences between infarcted and remote areas were tested by using the Wilcoxon signed rank test. RESULTS: Phantom studies demonstrated systematic behavior of the T1 measurements, and T1 error could be reduced to 1.3% ± 7.4 by using a simple linear correction algorithm. The pre- and postcontrast T1 of myocardium and blood showed narrow normal ranges. In the area of infarction, SALLI demonstrated hypokinesia (on cine images), myocardial edema (on precontrast T1 maps), and myocardial necrosis (on postcontrast T1 maps and late gadolinium enhancement images). CONCLUSION: An MR imaging method enabling simultaneous generation of cardiac T1 maps and cine and inversion recovery-prepared images at high heart rates is presented. SALLI allows for simultaneous and time-efficient assessment of cardiac T1 behavior, function, and late gadolinium enhancement at high heart rates.

Flow-sensitive four-dimensional magnetic resonance imaging facilitates and improves the accurate diagnosis of partial anomalous pulmonary venous drainage.

OBJECTIVES: To assess if flow-sensitive four-dimensional velocity-encoded cine magnetic resonance imaging adds value in diagnosing patients with suspected partial anomalous pulmonary venous drainage. METHODS: In six patients with echocardiographically suspected partial anomalous pulmonary venous drainage, anatomy was evaluated using standard magnetic resonance imaging including angiography. Functional analysis included shunt calculations from flow measurements. We used four-dimensional velocity-encoded cine magnetic resonance imaging for visualisation of maldraining pulmonary veins and quantification of flow via the maldraining veins and interatrial communications, if present. RESULTS: In all patients, the diagnosis of partial anomalous pulmonary venous drainage was confirmed by standard magnetic resonance imaging. Shunt volumes ranged from 1.4:1 to 4.7:1. Drainage sites were the superior caval vein (n = 5) or the vertical vein (n = 1). Multiple maldraining pulmonary veins were found in three patients. Pulmonary arteries and veins could be clearly distinguished by selective visualisation using four-dimensional velocity-encoded cine magnetic resonance imaging. Flow measured individually in maldraining pulmonary veins in six patients and across the interatrial communication in three patients revealed a percentage of the overall shunt volume of 30-100% and 58-70%, respectively. CONCLUSION: Selective visualisation of individual vessels and their flow characteristics by four-dimensional velocity-encoded cine magnetic resonance imaging facilitates in distinguishing adjacent pulmonary arteries and veins and thus improves the accurate diagnosis of maldraining pulmonary veins. By detailed quantification of shunt volumes, additional information for planning of treatment strategies is provided. This method adds clinical value and might replace contrast-enhanced magnetic resonance angiography in these patients in the future.

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.