Detection of hypoplastic left heart syndrome anatomy from cardiovascular magnetic resonance images using machine learning.

OBJECTIVE: The prospect of being able to gain relevant information from cardiovascular magnetic resonance (CMR) image analysis automatically opens up new potential to assist the evaluating physician. For machine-learning-based classification of complex congenital heart disease, only few studies have used CMR. MATERIALS AND METHODS: This study presents a tailor-made neural network architecture for detection of 7 distinctive anatomic landmarks in CMR images of patients with hypoplastic left heart syndrome (HLHS) in Fontan circulation or healthy controls and demonstrates the potential of the spatial arrangement of the landmarks to identify HLHS. The method was applied to the axial SSFP CMR scans of 46 patients with HLHS and 33 healthy controls. RESULTS: The displacement between predicted and annotated landmark had a standard deviation of 8-17 mm and was larger than the interobserver variability by a factor of 1.1-2.0. A high overall classification accuracy of 98.7% was achieved. DISCUSSION: Decoupling the identification of clinically meaningful anatomic landmarks from the actual classification improved transparency of classification results. Information from such automated analysis could be used to quickly jump to anatomic positions and guide the physician more efficiently through the analysis depending on the detected condition, which may ultimately improve work flow and save analysis time.

Utility of Coronary Computed Tomography Angiography in Patients Undergoing Transcatheter Aortic Valve Implantation: A Meta-Analysis and Meta-Regression Based on Published Data from 7458 Patients.

BACKGROUND: Coronary CT angiography (CCTA) may detect coronary artery disease (CAD) in transcatheter aortic valve implantation (TAVI) patients and may obviate invasive coronary angiography (ICA) in selected patients. We assessed the diagnostic accuracy of CCTA for detecting CAD in TAVI patients based on published data. METHODS: Meta-analysis and meta-regression were performed based on a comprehensive electronic search, including relevant studies assessing the diagnostic accuracy of CCTA in the setting of TAVI patients compared to ICA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated on a patient and per segment level. RESULTS: Overall, 27 studies (total of 7458 patients) were included. On the patient level, the CCTA's pooled sensitivity and NPV were 95% (95% CI: 93-97%) and 97% (95% CI: 95-98%), respectively, while the specificity and PPV were at 73% (95% CI: 62-82%) and 64% (95% CI: 57-71%), respectively. On the segmental coronary vessel level, the sensitivity and NPV were 90% (95% CI: 79-96%) and 98% (95% CI: 97-99%). CONCLUSIONS: This meta-analysis highlights CCTA's potential as a first-line diagnostic tool although its limited PPV and specificity may pose challenges when interpreting heavily calcified arteries. This study underscores the need for further research and protocol standardization in this area.

Continuous synthesis of E. coli genome sections and Mb-scale human DNA assembly.

Whole-genome synthesis provides a powerful approach for understanding and expanding organism function1-3. To build large genomes rapidly, scalably and in parallel, we need (1) methods for assembling megabases of DNA from shorter precursors and (2) strategies for rapidly and scalably replacing the genomic DNA of organisms with synthetic DNA. Here we develop bacterial artificial chromosome (BAC) stepwise insertion synthesis (BASIS)-a method for megabase-scale assembly of DNA in Escherichia coli episomes. We used BASIS to assemble 1.1 Mb of human DNA containing numerous exons, introns, repetitive sequences, G-quadruplexes, and long and short interspersed nuclear elements (LINEs and SINEs). BASIS provides a powerful platform for building synthetic genomes for diverse organisms. We also developed continuous genome synthesis (CGS)-a method for continuously replacing sequential 100 kb stretches of the E. coli genome with synthetic DNA; CGS minimizes crossovers1,4 between the synthetic DNA and the genome such that the output for each 100 kb replacement provides, without sequencing, the input for the next 100 kb replacement. Using CGS, we synthesized a 0.5 Mb section of the E. coli genome-a key intermediate in its total synthesis1-from five episomes in 10 days. By parallelizing CGS and combining it with rapid oligonucleotide synthesis and episome assembly5,6, along with rapid methods for compiling a single genome from strains bearing distinct synthetic genome sections1,7,8, we anticipate that it will be possible to synthesize entire E. coli genomes from functional designs in less than 2 months.

The genomic and bioclimatic characterization of Ethiopian barley (Hordeum vulgare L.) unveils challenges and opportunities to adapt to a changing climate.

The climate crisis is impacting agroecosystems and threatening food security of millions of smallholder farmers. Understanding the potential for current and future climatic adaptation of local crop agrobiodiversity may guide breeding efforts and support resilience of agriculture. Here, we combine a genomic and climatic characterization of a large collection of traditional barley varieties from Ethiopia, a staple for local smallholder farmers cropping in challenging environments. We find that the genomic diversity of barley landraces can be partially traced back to geographic and environmental diversity of the landscape. We employ a machine learning approach to model Ethiopian barley adaptation to current climate and to identify areas where its existing diversity may not be well adapted in future climate scenarios. We use this information to identify optimal trajectories of assisted migration compensating to detrimental effects of climate change, finding that Ethiopian barley diversity bears opportunities for adaptation to the climate crisis. We then characterize phenology traits in the collection in two common garden experiments in Ethiopia, using genome-wide association approaches to identify genomic loci associated with timing of flowering and maturity of the spike. We combine this information with genotype-environment associations finding that loci involved in flowering time may also explain environmental adaptation. Our data show that integrated genomic, climatic, and phenotypic characterizations of agrobiodiversity may provide breeding with actionable information to improve local adaptation in smallholder farming systems.

Reference Values for Pediatric Atrial Volumes Assessed by Steady-State Free-Precession Magnetic Resonance Imaging Using Monoplane and Biplane Area-Length Methods.

BACKGROUND: Measurement of atrial volumes by MRI is becoming increasingly important in pediatric cardiac disorders. However, MRI normal values for atrial volumes in children are lacking. PURPOSE: To establish pediatric reference values for atrial volumes. STUDY TYPE: Retrospective. SUBJECTS: A total of 155 healthy children from two large institutions (103 male, age 13.9 ± 2.8 years, range 4-18 years). FIELD STRENGTH/SEQUENCE: A 1.5 T; balanced steady-state free precession (bSSFP) sequence. ASSESSMENT: The monoplane and biplane area-length methods were used to measure minimal and maximal left and right atrial volumes (LAmin , LAmax , RAmin , and RAmax ) from four-chamber (4ch) and two-chamber (2ch) MR cine images. Centile charts and tables for atrial volumes were created. STATISTICAL TESTS: Descriptive statistics, lambda-mu-sigma (LMS)-method of Cole and Green, univariable and multivariable linear regression models. A P value < 0.05 was considered to be statistically significant. RESULTS: In the multivariable linear model, body surface area was significantly associated with all atrial volumes and sex was significantly associated with RA volumes, LA volumes measured in the 2ch-view as well as biplane LAmax. Average atrial volumes measured: monoplane 4ch: LAmin 13.1 ± 4.8 mL/m2 , LAmax 33.4 ± 8.8 mL/m2 , RAmin 18.5 ± 6.8 mL/m2 , RAmax 33.2 ± 9.6 mL/m2 ; monoplane 2ch: LAmin 12.7 ± 4.9 mL/m2 , LAmax 30.5 ± 9.5 mL/m2 ; biplane: LAmin 12.3 ± 4.5 mL/m2 , LAmax 30.9 ± 8.7 mL/m2 . DATA CONCLUSION: Pediatric MRI reference values for atrial volumes have been provided. TECHNICAL EFFICACY: 2 EVIDENCE LEVEL: 4.

Pediatric Cardiac Magnetic Resonance Reference Values for Biventricular Volumes Derived From Different Contouring Techniques.

BACKGROUND: Measurement of ventricular volumes and function using MRI is an important tool in pediatric congenital heart disease. However, normal values for children are sparce and analysis methods are inconsistent. PURPOSE: To propose biventricular reference values in children for two MRI postprocessing (contouring) techniques. STUDY TYPE: Retrospective. SUBJECTS: A total of 154 children from two institutions (13.9 ± 2.8 years; 101 male) that were referred for a clinical MRI study. FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession (bSSFP) sequence. ASSESSMENT: Left ventricular (LV) and right ventricular (RV) end-diastolic and end-systolic volumes (LVEDV, LVESV, RVEDV, RVESV) and end-diastolic and end-systolic myocardial mass (LVEDMM, LVESMM, RVEDMM, RVESMM) were measured from short-axis images using two contouring techniques: 1) papillary muscles, trabeculations and the moderator band were included in the ventricular blood volume and excluded from the myocardial mass, 2) papillary muscles, trabeculations and the moderator band were excluded from the ventricular volume and included in the ventricular mass. STATISTICAL TESTS: Univariable and multivariable linear regression models were used to evaluate relationships between sex, weight, height, body surface area (BSA) and age and volumetric results. Reference graphs and tables were created with the LMS-method. Contouring techniques were compared by intraclass correlation, regression analysis and Bland-Altman plots. A P value < 0.05 was considered statistically significant. RESULTS: Height and BSA were significantly associated with LVESV (method 1) and with LVEDV and RVEDV (method 2). LVESV (method 2), RVESV (both methods), RVEDV (method 1), and LVEDMM and RVEDMM (both methods), showed significant associations with height and weight. LVSV and RVSV (both methods) were significantly associated with BSA and weight. RVESV (method 1) was significantly associated with age. Gender showed significant associations for all parameters. DATA CONCLUSION: The proposed pediatric reference values can be used in the diagnosis and follow-up of congenital or acquired heart disease and for research purposes. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Serial Assessment of Right Ventricular Deformation in Patients With Hypoplastic Left Heart Syndrome: A Cardiovascular Magnetic Resonance Feature Tracking Study.

Background As right ventricular dysfunction is a major cause of adverse outcome in patients with hypoplastic left heart syndrome, the aim was to assess right ventricular function and deformation after Fontan completion by performing 2-dimensional cardiovascular magnetic resonance feature tracking in serial cardiovascular magnetic resonance studies. Methods and Results Cardiovascular magnetic resonance examinations of 108 patients with hypoplastic left heart syndrome (female: 31) were analyzed. Short-axis cine images were used for right ventricular volumetry. Two-dimensional cardiovascular magnetic resonance feature tracking was performed using long-axis and short-axis cine images to measure myocardial global longitudinal, circumferential, and radial strain. All patients had at least 2 cardiovascular magnetic resonance examinations after Fontan completion and 41 patients had 3 examinations. Global strain values and right ventricular ejection fraction decreased from the first to the third examination with a significant decline in global longitudinal strain from the first examination to the second examination (median, first, and third quartile: -18.8%, [-20.5;-16.5] versus -16.9%, [-19.3;-14.7]) and from the first to the third examination in 41 patients (-18.6%, [-20.9;-15.7] versus -15.8%, [-18.7;-12.6]; P-values <0.004). Right ventricular ejection fraction decreased significantly from the first to the third examination (55.4%, [49.8;59.3] versus 50.2%, [45.0;55.9]; P<0.002) and from the second to the third examination (53.8%, [47.2;58.7] versus 50.2%, [45.0;55.9]; P<0.0002). Conclusions Serial assessment of cardiovascular magnetic resonance studies in patients with hypoplastic left heart syndrome after Fontan completion demonstrates a significant reduction in global strain values and right ventricular ejection fraction at follow-up. The significant reduction in global longitudinal strain between the first 2 examinations with non-significant changes in right ventricular ejection fraction suggest that global longitudinal strain measured by 2-dimensional cardiovascular magnetic resonance feature tracking might be a superior technique for the detection of changes in myocardial function.

Myocardial Deformation in the Pediatric Age Group: Normal Values for Strain and Strain Rate Using 2D Magnetic Resonance Feature Tracking.

BACKGROUND: Myocardial deformation can be assessed from routine cardiac magnetic resonance (MR) images using two-dimensional feature tracking (2D-FT). Although reference values are essential for implementation of strain imaging in clinical practice, data for the healthy pediatric age group are limited. PURPOSE: To provide pediatric MR reference values for strain and strain rate for all four heart chambers. STUDY TYPE: Retrospective. SUBJECTS: One hundred and fifty-seven healthy children from two institutions (102 male, age 4.7-18 years). FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession sequence. ASSESSMENT: Left ventricular (LV) global and regional longitudinal, circumferential, and radial strain and strain rate as well as right ventricular (RV) and atrial global and regional longitudinal strain and strain rate were measured in two-, three-, and four-chamber views and the short axis stack. The relationships between strain parameters and age, height, weight, and gender were investigated. Age- and height-specific centile curves and tables were created for LV strain and strain rate. For all other global strain parameters, the mean was calculated as a reference. STATISTICAL TESTS: Lambda-mu-sigma (LMS)-method of Cole and Green, univariable, and multivariable linear regression models. A P value <0.05 was considered to be statistically significant. RESULTS: Age, height and weight had a significant influence on LV global strain values. These parameters also showed an influence on RV strain but only in boys (girls P = 0.12) and none of the variables had a significant influence on atrial strain (P = 0.19-0.49). Gender differences were only found for RV strain values. DATA CONCLUSION: Pediatric potential reference values for myocardial deformation parameters of both ventricles and atria are provided. The values may serve as a reference in future studies and clinical practice. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

Synthetic genomics for curing genetic diseases.

From the beginning of the genome sequencing era, it has become increasingly evident that genetics plays a role in all diseases, of which only a minority are single-gene disorders, the most common target of current gene therapies. However, the majority of people have some kind of health problems resulting from congenital genetic mutations (over 6000 diseases have been associated to genes, https://www.omim.org/statistics/geneMap) and most genetic disorders are rare and only incompletely understood. The vision and techniques applied to the synthesis of genomes may help to address unmet medical needs from a chromosome and genome-scale perspective. In this chapter, we address the potential therapy of genetic diseases from a different outlook, in which we no longer focus on small gene corrections but on higher-order tools for genome manipulation. These will play a crucial role in the next years, as they prelude to a much deeper understanding of the architecture of the human genome and a more accurate modeling of human diseases, offering new therapeutic opportunities.

Coronary artery ectasia in a child after arterial switch operation for transposition of the great arteries and suspected multisystem inflammatory syndrome in children associated with COVID-19: a case report.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) with features resembling Kawasaki disease has been reported in association with coronavirus disease 2019 (COVID-19). CASE SUMMARY: We report the rare case of a 22 months old boy with a history of operated simple transposition of the great arteries (TGA), who developed features of MIS-C likely to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and involving the coronary arteries. Cardiovascular magnetic resonance imaging and cardiac catheterization showed long-distance ectasia of both coronary arteries after their origins and an origin stenosis of the right coronary artery with a perfusion defect. The patient was treated with oral anticoagulation together with antiplatelet therapy and remains under careful monitoring. DISCUSSION: This rare case demonstrates that also patients with TGA after the arterial switch operation (ASO) can develop coronary artery dilatation in association with MIS-C. The most interesting finding in this patient was that the origins of the reimplanted coronary arteries were not dilated. We speculate that scar tissue formation in the area of coronary artery transfer after ASO has prevented proximal coronary artery dilation.

Cardiovascular magnetic resonance normal values in children for biventricular wall thickness and mass.

BACKGROUND: Pediatric patients are becoming increasingly referred for cardiovascular magnetic resonance (CMR). Measurement of ventricular wall thickness is typically part of the assessment and can be of diagnostic importance, e.g. in arterial hypertension. However, normal values for left ventricular (LV) and right ventricular (RV) wall thickness in pediatric patients are lacking. The aim of this study was to establish pediatric centile charts for segmental LV and RV myocardial thickness in a retrospective multicenter CMR study. METHODS: CMR was performed in 161 healthy children and adolescents with an age range between 6 and 18 years from two centers in the UK and Germany as well as from a previously published CMR project of the German Competence Network for Congenital Heart Defects. LV myocardial thickness of 16 segments was measured on the short axis stack using the American Heart Association segmentation model. In addition, the thickness of the RV inferior and anterior free wall as well as biventricular mass was measured. RESULTS: The mean age (standard deviation) of the subjects was 13.6 (2.9) years, 64 (39.7%) were female. Myocardial thickness of the basal septum (basal antero- and inferoseptal wall) was 5.2 (1.1) mm, and the basal lateral wall (basal antero- and inferolateral) measured 5.1 (1.2) mm. Mid-ventricular septum (antero- and inferoseptal wall) measured 5.5 (1.2) mm, and mid-ventricular lateral wall (antero- and inferolateral wall) was 4.7 (1.2) mm. Separate centile charts for boys and girls for all myocardial segments and myocardial mass were created because gender was significantly correlated with LV myocardial thickness (p < 0.001 at basal level, p = 0.001 at midventricular level and p = 0.005 at the apex) and biventricular mass (LV, p < 0.001; RV, p < 0.001). CONCLUSION: We established CMR normal values of segmental myocardial thickness and biventricular mass in children and adolescents. Our data are of use for the detection of abnormal myocardial properties and can serve as a reference in future studies and clinical practice.

Apical hypertrophic cardiomyopathy with subendocardial late gadolinium enhancement in an adolescent.

A 17-year-old boy with a history of dyspnea attacks and chest pain was referred to our paediatric cardiology department. Electrocardiogram at presentation showed T-wave inversion in the inferior leads. Cardiovascular magnetic resonance imaging revealed the rare diagnosis of apical hypertrophic cardiomyopathy with subendocardial late gadolinium enhancement, missed by echocardiography.