Congenital heart defect (CHD) is a significant, rapidly emerging global problem in child health and a leading cause of neonatal and childhood death. Prenatal detection of CHDs with the help of ultrasound allows better perinatal management of such pregnancies, leading to reduced neonatal mortality, morbidity and developmental complications. However, there is a wide variation in reported fetal heart problem detection rates from 34% to 85%, with some low- and middle-income countries detecting as low as 9.3% of cases before birth. Research has shown that deep learning-based or more general artificial intelligence (AI) models can support the detection of fetal CHDs more rapidly than humans performing ultrasound scan. Progress in this AI-based research depends on the availability of large, well-curated and diverse data of ultrasound images and videos of normal and abnormal fetal hearts. Currently, CHD detection based on AI models is not accurate enough for practical clinical use, in part due to the lack of ultrasound data available for machine learning as CHDs are rare and heterogeneous, the retrospective nature of published studies, the lack of multicentre and multidisciplinary collaboration, and utilisation of mostly standard planes still images of the fetal heart for AI models. Our aim is to develop AI models that could support clinicians in detecting fetal CHDs in real time, particularly in nonspecialist or low-resource settings where fetal echocardiography expertise is not readily available. We have designed the Clinical Artificial Intelligence Fetal Echocardiography (CAIFE) study as an international multicentre multidisciplinary collaboration led by a clinical and an engineering team at the University of Oxford. This study involves five multicountry hospital sites for data collection (Oxford, UK (n=1), London, UK (n=3) and Southport, Australia (n=1)). We plan to curate 14 000 retrospective ultrasound scans of fetuses with normal hearts (n=13 000) and fetuses with CHDs (n=1000), as well as 2400 prospective ultrasound cardiac scans, including the proposed research-specific CAIFE 10 s video sweeps, from fetuses with normal hearts (n=2000) and fetuses diagnosed with major CHDs (n=400). This gives a total of 16 400 retrospective and prospective ultrasound scans from the participating hospital sites. We will build, train and validate computational models capable of differentiating between normal fetal hearts and those diagnosed with CHDs and recognise specific types of CHDs. Data will be analysed using statistical metrics, namely, sensitivity, specificity and accuracy, which include calculating positive and negative predictive values for each outcome, compared with manual assessment. We will disseminate the findings through regional, national and international conferences and through peer-reviewed journals. The study was approved by the Health Research Authority, Care Research Wales and the Research Ethics Committee (Ref: 23/EM/0023; IRAS Project ID: 317510) on 8 March 2023. All collaborating hospitals have obtained the local trust research and development approvals.

Although genetic variant effects often interact nonadditively, strategies to uncover epistasis remain in their infancy. Here we develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy, using deep learning-derived left ventricular mass estimates from 29,661 UK Biobank cardiac magnetic resonance images. We report epistatic variants near CCDC141, IGF1R, TTN and TNKS, identifying loci deemed insignificant in genome-wide association studies. Functional genomic and integrative enrichment analyses reveal that genes mapped from these loci share biological process gene ontologies and myogenic regulatory factors. Transcriptomic network analyses using 313 human hearts demonstrate strong co-expression correlations among these genes in healthy hearts, with significantly reduced connectivity in failing hearts. To assess causality, RNA silencing in human induced pluripotent stem cell-derived cardiomyocytes, combined with novel microfluidic single-cell morphology analysis, confirms that cardiomyocyte hypertrophy is nonadditively modifiable by interactions between CCDC141, TTN and IGF1R. Our results expand the scope of cardiac genetic regulation to epistasis.

Computed tomography is an inadequate method for detecting myocardial focal scar (MFS) due to its moderate density resolution, which is insufficient for distinguishing MFS from artificial beam-hardening (BH). Virtual monochromatic images (VMIs) of dual-energy coronary computed tomography angiography (DECCTA) provide a variety of diagnostic information with significant potential for detecting myocardial lesions. The aim of this study was to assess whether radiomics analysis in VMIs of DECCTA can help distinguish MFS from BH. A prospective cohort of patients who were suspected with an old myocardial infarction was assembled at two different centers between Janurary 2021 and June 2024. MFS and BH segmentation and radiomics feature extraction and selection were performed on VMIs images, and four machine learning classifiers were constructed using selected strongest features. Subsequently, an independent validation was conducted, and a subjective diagnosis of the validation set was provided by an radiologist. The AUC was used to assess the performance of the radiomics models. The training set included 57 patients from center 1 (mean age, 54 years +/- 9, 55 men), and the external validation set included 10 patients from center 2 (mean age, 59 years +/- 10, 9 men). The radiomics models exhibited the highest AUC value of 0.937 (expressed at 130 keV VMIs), while the radiologist demonstrated the highest AUC value of 0.734 (expressed at 40 keV VMIs). The integration of radiomic features derived from VMIs of DECCTA with machine learning algorithms has the potential to improve the efficiency of distinguishing MFS from BH.

Cardiac amyloidosis is associated with poor outcomes and is caused by the interstitial deposition of misfolded proteins, typically ATTR (transthyretin) or AL (light chains). Although specific therapies during early disease stages exist, the diagnosis is often only established at an advanced stage. Cardiovascular magnetic resonance (CMR) is the gold standard for imaging suspected myocardial disease. However, differentiating cardiac amyloidosis from hypertrophic cardiomyopathy may be challenging, and a reliable method for an image-based classification of amyloidosis subtypes is lacking. This study sought to investigate a CMR machine learning (ML) algorithm to identify and distinguish cardiac amyloidosis. This retrospective, multicenter, multivendor feasibility study included consecutive patients diagnosed with hypertrophic cardiomyopathy or AL/ATTR amyloidosis and healthy volunteers. Standard clinical information, semiautomated CMR imaging data, and qualitative CMR features were integrated into a trained ML algorithm. Four hundred participants (95 healthy, 94 hypertrophic cardiomyopathy, 95 AL, and 116 ATTR) from 56 institutions were included (269 men aged 58.5 [48.4-69.4] years). A 3-stage ML screening cascade sequentially differentiated healthy volunteers from patients, then hypertrophic cardiomyopathy from amyloidosis, and then AL from ATTR. The ML algorithm resulted in an accurate differentiation at each step (area under the curve, 1.0, 0.99, and 0.92, respectively). After reducing included data to demographics and imaging data alone, the performance remained excellent (area under the curve, 0.99, 0.98, and 0.88, respectively), even after removing late gadolinium enhancement imaging data from the model (area under the curve, 1.0, 0.95, 0.86, respectively). A trained ML model using semiautomated CMR imaging data and patient demographics can accurately identify cardiac amyloidosis and differentiate subtypes.

Recent advancements in artificial intelligence (AI) have revolutionized cardiovascular medicine, particularly through integration with computed tomography (CT), magnetic resonance imaging (MRI), electrocardiography (ECG) and ultrasound (US). Deep learning architectures, including convolutional neural networks and generative adversarial networks, enable automated analysis of medical imaging and physiological signals, surpassing human capabilities in diagnostic accuracy and workflow efficiency. However, critical challenges persist, including the inability to validate input data accuracy, which may propagate diagnostic errors. This review highlights AI's transformative potential in precision diagnostics while underscoring the need for robust validation protocols to ensure clinical reliability. Future directions emphasize hybrid models integrating multimodal data and adaptive algorithms to refine personalized cardiovascular care.

<b>BACKGROUND.</b> The importance of including the thoracic aortic calcification (TAC), in addition to coronary artery calcification (CAC), in prognostic assessments has been difficult to determine, partly due to greater challenge in performing standardized TAC assessments. <b>OBJECTIVE.</b> The purpose of this study was to evaluate long-term prognostic implications of TAC assessed using artificial intelligence (AI)-based quantification on routine chest CT in a screening population. <b>METHODS.</b> This retrospective study included 7404 asymptomatic individuals (median age, 53.9 years; 5875 men, 1529 women) who underwent nongated noncontrast chest CT as part of a national general health screening program at one of two centers from January 2007 to December 2014. A commercial AI program quantified TAC and CAC using Agatston scores, which were stratified into categories. Radiologists manually quantified TAC and CAC in 2567 examinations. The role of AI-based TAC categories in predicting major adverse cardiovascular events (MACE) and all-cause mortality (ACM), independent of AI-based CAC categories as well as clinical and laboratory variables, was assessed by multivariable Cox proportional hazards models using data from both centers and concordance statistics from prognostic models developed and tested using center 1 and center 2 data, respectively. <b>RESULTS.</b> AI-based and manual quantification showed excellent agreement for TAC and CAC (concordance correlation coefficient: 0.967 and 0.895, respectively). The median observation periods were 7.5 years for MACE (383 events in 5342 individuals) and 11.0 years for ACM (292 events in 7404 individuals). When adjusted for AI-based CAC categories along with clinical and laboratory variables, the risk for MACE was not independently associated with any AI-based TAC category; risk of ACM was independently associated with AI-based TAC score of 1001-3000 (HR = 2.14, <i>p</i> = .02) but not with other AI-based TAC categories. When prognostic models were tested, the addition of AI-based TAC categories did not improve model fit relative to models containing clinical variables, laboratory variables, and AI-based CAC categories for MACE (concordance index [C-index] = 0.760-0.760, <i>p</i> = .81) or ACM (C-index = 0.823-0.830, <i>p</i> = .32). <b>CONCLUSION.</b> The addition of TAC to models containing CAC provided limited improvement in risk prediction in an asymptomatic screening population undergoing CT. <b>CLINICAL IMPACT.</b> AI-based quantification provides a standardized approach for better understanding the potential role of TAC as a predictive imaging biomarker.

Left ventricular non-compaction is a cardiac condition marked by excessive trabeculae in the left ventricle's inner wall. Although various methods exist to measure these structures, the medical community still lacks consensus on the best approach. Previously, we developed DL-LVTQ, a tool based on a UNet neural network, to quantify trabeculae in this region. In this study, we expand the dataset to include new patients with Titin cardiomyopathy and healthy individuals with fewer trabeculae, requiring retraining of our models to enhance predictions. We also propose ViTUNeT, a neural network architecture combining U-Net and Vision Transformers to segment the left ventricle more accurately. Additionally, we train a YOLOv8 model to detect the ventricle and integrate it with ViTUNeT model to focus on the region of interest. Results from ViTUNet and YOLOv8 are similar to DL-LVTQ, suggesting dataset quality limits further accuracy improvements. To test this, we analyze MRI images and develop a method using two YOLOv8 models to identify and remove problematic images, leading to better results. Combining YOLOv8 with deep learning networks offers a promising approach for improving cardiac image analysis and segmentation.

Despite its potential to improve the assessment of cardiovascular diseases, 4D Flow CMR is hampered by long scan times. 4D Flow CMR is conventionally acquired with three motion encodings and one reference encoding, as the 3-dimensional velocity data are obtained by subtracting the phase of the reference from the phase of the motion encodings. In this study, we aim to use deep learning to predict the reference encoding from the three motion encodings for cardiovascular 4D Flow. A U-Net was trained with adversarial learning (U-Net_ADV) and with a velocity frequency-weighted loss function (U-Net_VEL) to predict the reference encoding from the three motion encodings obtained with a non-symmetric velocity-encoding scheme. Whole-heart 4D Flow datasets from 126 patients with different types of cardiomyopathies were retrospectively included. The models were trained on 113 patients with a 5-fold cross-validation, and tested on 13 patients. Flow volumes in the aorta and pulmonary artery, mean and maximum velocity, total and maximum turbulent kinetic energy at peak systole in the cardiac chambers and main vessels were assessed. 3-dimensional velocity data reconstructed with the reference encoding predicted by deep learning agreed well with the velocities obtained with the reference encoding acquired at the scanner for both models. U-Net_ADV performed more consistently throughout the cardiac cycle and across the test subjects, while U-Net_VEL performed better for systolic velocities. Comprehensively, the largest error for flow volumes, maximum and mean velocities was -6.031% for maximum velocities in the right ventricle for the U-Net_ADV, and -6.92% for mean velocities in the right ventricle for U-Net_VEL. For total turbulent kinetic energy, the highest errors were in the left ventricle (-77.17%) for the U-Net_ADV, and in the right ventricle (24.96%) for the U-Net_VEL, while for maximum turbulent kinetic energy were in the pulmonary artery for both models, with a value of -15.5% for U-Net_ADV and 15.38% for the U-Net_VEL. Deep learning-enabled referenceless 4D Flow CMR permits velocities and flow volumes quantification comparable to conventional 4D Flow. Omitting the reference encoding reduces the amount of acquired data by 25%, thus allowing shorter scan times or improved resolution, which is valuable for utilization in the clinical routine.

BackgroundDelays in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) contribute to the significant morbidity of the condition, especially in the era of disease-modifying therapies. Screening for ATTR-CM with AI and other algorithms may improve timely diagnosis, but these algorithms have not been directly compared. ObjectivesThe aim of this study was to compare the performance of four algorithms for ATTR-CM detection in a heart failure population and assess the risk for harms due to model bias. MethodsWe identified patients in an integrated health system from 2010-2022 with ATTR-CM and age- and sex-matched them to controls with heart failure to target 5% prevalence. We compared the performance of a claims-based random forest model (Huda et al. model), a regression-based score (Mayo ATTR-CM), and two deep learning echo models (EchoNet-LVH and EchoGo(R) Amyloidosis). We evaluated for bias using standard fairness metrics. ResultsThe analytical cohort included 176 confirmed cases of ATTR-CM and 3192 control patients with 79.2% self-identified as White and 9.0% as Black. The Huda et al. model performed poorly (AUC 0.49). Both deep learning echo models had a higher AUC when compared to the Mayo ATTR-CM Score (EchoNet-LVH 0.88; EchoGo Amyloidosis 0.92; Mayo ATTR-CM Score 0.79; DeLong P<0.001 for both). Bias auditing met fairness criteria for equal opportunity among patients who identified as Black. ConclusionsDeep learning, echo-based models to detect ATTR-CM demonstrated best overall discrimination when compared to two other models in external validation with low risk of harms due to racial bias.

Multiple parametric imaging in positron emission tomography (PET) is challenging due to the noisy dynamic data and the complex mapping to kinetic parameters. Although methods like direct parametric reconstruction have been proposed to improve the image quality, limitations persist, particularly for nonlinear and small-value micro-parameters (e.g., k₂, k₃). This study presents a novel unsupervised deep learning approach to reconstruct and improve the quality of these micro-parameters. We proposed a direct parametric image reconstruction model, DIP-PM, integrating deep image prior (DIP) with a parameter magnification (PM) strategy. The model employs a U-Net generator to predict multiple parametric images using a CT image prior, with each output channel subsequently magnified by a factor to adjust the intensity. The model was optimized with a log-likelihood loss computed between the measured projection data and forward projected data. Two tracer datasets were simulated for evaluation: ⁸²Rb data using the 1-tissue compartment (1 TC) model and ¹⁸F-FDG data using the 2-tissue compartment (2 TC) model, with 10-fold magnification applied to the 1 TC k₂ and the 2 TC k₃, respectively. DIP-PM was compared to the indirect method, direct algorithm (OTEM) and the DIP method without parameter magnification (DIP-only). Performance was assessed on phantom data using peak signal-to-noise ratio (PSNR), normalized root mean square error (NRMSE) and structural similarity index (SSIM), as well as on real ¹⁸F-FDG scan from a male subject. For the 1 TC model, OTEM performed well in K₁ reconstruction, but both indirect and OTEM methods showed high noise and poor performance in k₂. The DIP-only method suppressed noise in k₂, but failed to reconstruct fine structures in the myocardium. DIP-PM outperformed other methods with well-preserved detailed structures, particularly in k₂, achieving the best metrics (PSNR: 19.00, NRMSE: 0.3002, SSIM: 0.9289). For the 2 TC model, traditional methods exhibited high noise and blurred structures in estimating all nonlinear parameters (K₁, k₂, k₃), while DIP-based methods significantly improved image quality. DIP-PM outperformed all methods in k₃ (PSNR: 21.89, NRMSE: 0.4054, SSIM: 0.8797), and consequently produced the most accurate 2 TC K_i images (PSNR: 22.74, NRMSE: 0.4897, SSIM: 0.8391). On real FDG data, DIP-PM also showed evident advantages in estimating K₁, k₂ and k₃ while preserving myocardial structures. The results underscore the efficacy of the DIP-based direct parametric imaging in generating and improving quality of PET parametric images. This study suggests that the proposed DIP-PM method with the parameter magnification strategy can enhance the fidelity of nonlinear micro-parameter images.