Association of enlarged extra-axial spaces and subdural hemorrhage in preterm infants at term-equivalent age.

To determine the incidence of enlarged extra-axial space (EES) and its association with subdural hemorrhage (SDH) in a regional cohort of preterm infants. As part of a prospective cohort study of 395 preterm infants, brain magnetic resonance imaging (MRI) was collected on each infant at term-equivalent age. Six preterm infants showed evidence of SDH. We reviewed the MRIs to identify the incidence of EES in these 6 infants and the cohort broadly. We then completed a retrospective chart review of the 6 infants to identify any concerns for non-accidental trauma (NAT) since the MRI was obtained. The incidence of SDH in the cohort was 1.6%. The incidence of EES was 48.1% including all 6 infants with SDH. The incidence of SDH in infants with EES was 3.2%. The retrospective chart review of the 6 infants did not yield any evidence of NAT. The incidence of EES and SDH in our cohort was significantly higher than similar cohorts of term infants, demonstrating an increased risk in preterm infants. The incidence of SDH in infants with EES was greater than in the total cohort, suggesting that it is a risk factor for asymptomatic SDH in preterm infants.

Artificial Intelligence Provides Accurate Quantification of Thoracic Aortic Enlargement and Dissection in Chest CT.

This study evaluated a deep neural network (DNN) algorithm for automated aortic diameter quantification and aortic dissection detection in chest computed tomography (CT). A total of 100 patients (median age: 67.0 [interquartile range 55.3/73.0] years; 60.0% male) with aortic aneurysm who underwent non-enhanced and contrast-enhanced electrocardiogram-gated chest CT were evaluated. All the DNN measurements were compared to manual assessment, overall and between the following subgroups: (1) ascending (AA) vs. descending aorta (DA); (2) non-obese vs. obese; (3) without vs. with aortic repair; (4) without vs. with aortic dissection. Furthermore, the presence of aortic dissection was determined (yes/no decision). The automated and manual diameters differed significantly (p < 0.05) but showed excellent correlation and agreement (r = 0.89; ICC = 0.94). The automated and manual values were similar in the AA group but significantly different in the DA group (p < 0.05), similar in obese but significantly different in non-obese patients (p < 0.05) and similar in patients without aortic repair or dissection but significantly different in cases with such pathological conditions (p < 0.05). However, in all the subgroups, the automated diameters showed strong correlation and agreement with the manual values (r > 0.84; ICC > 0.9). The accuracy, sensitivity and specificity of DNN-based aortic dissection detection were 92.1%, 88.1% and 95.7%, respectively. This DNN-based algorithm enabled accurate quantification of the largest aortic diameter and detection of aortic dissection in a heterogenous patient population with various aortic pathologies. This has the potential to enhance radiologists' efficiency in clinical practice.

Self-supervised learning for interventional image analytics: toward robust device trackers.

Purpose: The accurate detection and tracking of devices, such as guiding catheters in live X-ray image acquisitions, are essential prerequisites for endovascular cardiac interventions. This information is leveraged for procedural guidance, e.g., directing stent placements. To ensure procedural safety and efficacy, there is a need for high robustness/no failures during tracking. To achieve this, one needs to efficiently tackle challenges, such as device obscuration by the contrast agent or other external devices or wires and changes in the field-of-view or acquisition angle, as well as the continuous movement due to cardiac and respiratory motion. Approach: To overcome the aforementioned challenges, we propose an approach to learn spatio-temporal features from a very large data cohort of over 16 million interventional X-ray frames using self-supervision for image sequence data. Our approach is based on a masked image modeling technique that leverages frame interpolation-based reconstruction to learn fine inter-frame temporal correspondences. The features encoded in the resulting model are fine-tuned downstream in a light-weight model. Results: Our approach achieves state-of-the-art performance, in particular for robustness, compared to ultra optimized reference solutions (that use multi-stage feature fusion or multi-task and flow regularization). The experiments show that our method achieves a 66.31% reduction in the maximum tracking error against the reference solutions (23.20% when flow regularization is used), achieving a success score of 97.95% at a 3× faster inference speed of 42 frames-per-second (on GPU). In addition, we achieve a 20% reduction in the standard deviation of errors, which indicates a much more stable tracking performance. Conclusions: The proposed data-driven approach achieves superior performance, particularly in robustness and speed compared with the frequently used multi-modular approaches for device tracking. The results encourage the use of our approach in various other tasks within interventional image analytics that require effective understanding of spatio-temporal semantics.

Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates.

(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014-2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation (n = 94 before, n = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.

Anatomically aware dual-hop learning for pulmonary embolism detection in CT pulmonary angiograms.

Pulmonary Embolisms (PE) represent a leading cause of cardiovascular death. While medical imaging, through computed tomographic pulmonary angiography (CTPA), represents the gold standard for PE diagnosis, it is still susceptible to misdiagnosis or significant diagnosis delays, which may be fatal for critical cases. Despite the recently demonstrated power of deep learning to bring a significant boost in performance in a wide range of medical imaging tasks, there are still very few published researches on automatic pulmonary embolism detection. Herein we introduce a deep learning based approach, which efficiently combines computer vision and deep neural networks for pulmonary embolism detection in CTPA. Our method brings novel contributions along three orthogonal axes: (1) automatic detection of anatomical structures; (2) anatomical aware pretraining, and (3) a dual-hop deep neural net for PE detection. We obtain state-of-the-art results on the publicly available multicenter large-scale RSNA dataset.

A highly conserved tRNA modification contributes to C. albicans filamentation and virulence.

tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker's yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic Candida albicans and its much less pathogenic sister species, Candida dubliniensis, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits species-specific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C-the body temperature of the human host. A C. albicans HMA1 deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.IMPORTANCEFungal infections are on the rise worldwide, and their global burden on human life and health is frequently underestimated. Among them, the human commensal and opportunistic pathogen, Candida albicans, is one of the major causative agents of severe infections. Its virulence is closely linked to its ability to change morphologies from yeasts to hyphae. Here, this ability is linked-to our knowledge for the first time-to modifications of tRNA and translational efficiency. One tRNA-modifying enzyme, Hma1, plays a specific role in C. albicans and its ability to invade the host. This adds a so-far unknown layer of regulation to the fungal virulence program and offers new potential therapeutic targets to fight fungal infections.

A model of human neural networks reveals NPTX2 pathology in ALS and FTLD.

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2-5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3' untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.

Artificial intelligence in the neonatal intensive care unit: the time is now.

Artificial intelligence (AI) has the potential to revolutionize the neonatal intensive care unit (NICU) care by leveraging the large-scale, high-dimensional data that are generated by NICU patients. There is an emerging recognition that the confluence of technological progress, commercialization pathways, and rich data sets provides a unique opportunity for AI to make a lasting impact on the NICU. In this perspective article, we discuss four broad categories of AI applications in the NICU: imaging interpretation, prediction modeling of electronic health record data, integration of real-time monitoring data, and documentation and billing. By enhancing decision-making, streamlining processes, and improving patient outcomes, AI holds the potential to transform the quality of care for vulnerable newborns, making the excitement surrounding AI advancements well-founded and the potential for significant positive change stronger than ever before.

Deep Learning-Based Automated Labeling of Coronary Segments for Structured Reporting of Coronary Computed Tomography Angiography in Accordance With Society of Cardiovascular Computed Tomography Guidelines.

PURPOSE: To evaluate a novel deep learning (DL)-based automated coronary labeling approach for structured reporting of coronary artery disease according to the guidelines of the Society of Cardiovascular Computed Tomography (CT) on coronary CT angiography (CCTA). PATIENTS AND METHODS: A retrospective cohort of 104 patients (60.3 ± 10.7 y, 61% males) who had undergone prospectively electrocardiogram-synchronized CCTA were included. Coronary centerlines were automatically extracted, labeled, and validated by 2 expert readers according to Society of Cardiovascular CT guidelines. The DL algorithm was trained on 706 radiologist-annotated cases for the task of automatically labeling coronary artery centerlines. The architecture leverages tree-structured long short-term memory recurrent neural networks to capture the full topological information of the coronary trees by using a two-step approach: a bottom-up encoding step, followed by a top-down decoding step. The first module encodes each sub-tree into fixed-sized vector representations. The decoding module then selectively attends to the aggregated global context to perform the local assignation of labels. To assess the performance of the software, percentage overlap was calculated between the labels of the algorithm and the expert readers. RESULTS: A total number of 1491 segments were identified. The artificial intelligence-based software approach yielded an average overlap of 94.4% compared with the expert readers' labels ranging from 87.1% for the posterior descending artery of the right coronary artery to 100% for the proximal segment of the right coronary artery. The average computational time was 0.5 seconds per case. The interreader overlap was 96.6%. CONCLUSIONS: The presented fully automated DL-based coronary artery labeling algorithm provides fast and precise labeling of the coronary artery segments bearing the potential to improve automated structured reporting for CCTA.

World Health Organization MPOWER for tobacco control in India: a 6-year retrospective analysis.

Background: Prevalence and practices of tobacco usage in India are diverse and incongruent and Government of India has enacted various laws to overcome this burden. To make tobacco control measures effective and powerful, WHO introduced MPOWER in 2004 and India was one of the first countries that implemented the MPOWER. Objective: This study is aimed to quantify the implementation of MPOWER tobacco control policies in India. Material and Methods: In this retrospective analysis, data was gathered from the WHO MPOWER of India from 2015 to 2021. This analysis was based on the checklist which was designed previously by Iranian and international tobacco control specialists in their study on tobacco control. Results: In the present comparative analysis, India was categorized by scores and these were acquired from each indicator for each activity and 2021 year got the highest scores as compared to the previous year scores i.e. 27 in 2015. In context to individual indicators, noticeable increase in scores has been seen in both health warning on cigarette packages and adult daily smoking prevalence, whereas no progress was observed in smoking related policies. Conclusion: Although MPOWER programmes are widely accepted by the Indian government, but still substantial improvement in fewer sections is required.

Performing Quality Control on Magnetic Resonance Imaging Liver Fat/Iron Quantification Studies: A Critical Requirement.

OBJECTIVE: Nonalcoholic fatty liver and iron overload can lead to cirrhosis requiring early detection. Magnetic resonance (MR) imaging utilizing chemical shift-encoded sequences and multi-Time of Echo single-voxel spectroscopy (SVS) are frequently used for assessment. The purpose of this study was to assess various quality factors of technical acceptability and any deficiencies in technologist performance in these fat/iron MR quantification studies. METHODS: Institutional review board waived retrospective quality improvement review of 87 fat/iron MR studies performed over a 6-month period was evaluated. Technical acceptability/unacceptability for chemical shift-encoded sequences (q-Dixon and IDEAL-IQ) included data handling errors (missing maps), liver field coverage, fat/water swap, motion, or other artifacts. Similarly, data handling (missing table/spectroscopy), curve-fit, fat- and water-peak separation, and water-peak sharpness were evaluated for SVS technical acceptability. RESULTS: Data handling errors were found in 11% (10/87) of studies with missing maps or entire sequence (SVS or q-Dixon). Twenty-seven percent (23/86) of the q-Dixon/IDEAL-IQ were technically unacceptable (incomplete liver-field [39%], other artifacts [35%], significant/severe motion [18%], global fat/water swap [4%], and multiple reasons [4%]). Twenty-eight percent (21/75) of SVS sequences were unacceptable (water-peak broadness [67%], poor curve-fit [19%] overlapping fat and water peaks [5%], and multiple reasons [9%]). CONCLUSIONS: A high rate of preventable errors in fat/iron MR quantification studies indicates the need for routine quality control and evaluation of technologist performance and technical deficiencies that may exist within a radiology practice. Potential solutions such as instituting a checklist for technologists during each acquisition procedure and routine auditing may be required.

AI-based, automated chamber volumetry from gated, non-contrast CT.

BACKGROUND: Accurate chamber volumetry from gated, non-contrast cardiac CT (NCCT) scans can be useful for potential screening of heart failure. OBJECTIVES: To validate a new, fully automated, AI-based method for cardiac volume and myocardial mass quantification from NCCT scans compared to contrasted CT Angiography (CCTA). METHODS: Of a retrospectively collected cohort of 1051 consecutive patients, 420 patients had both NCCT and CCTA scans at mid-diastolic phase, excluding patients with cardiac devices. Ground truth values were obtained from the CCTA scans. RESULTS: The NCCT volume computation shows good agreement with ground truth values. Volume differences [95% CI ] and correlation coefficients were: -9.6 [-45; 26] mL, r â€‹= â€‹0.98 for LV Total, -5.4 [-24; 13] mL, r â€‹= â€‹0.95 for LA, -8.7 [-45; 28] mL, r â€‹= â€‹0.94 for RV, -5.2 [-27; 17] mL, r â€‹= â€‹0.92 for RA, -3.2 [-42; 36] mL, r â€‹= â€‹0.91 for LV blood pool, and -6.7 [-39; 26] g, r â€‹= â€‹0.94 for LV wall mass, respectively. Mean relative volume errors of less than 7% were obtained for all chambers. CONCLUSIONS: Fully automated assessment of chamber volumes from NCCT scans is feasible and correlates well with volumes obtained from contrast study.

Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA.

Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2*, a point mutation identified in a clinical baker's yeast isolate. Ncs2 is essential for 2-thiolation of tRNA and the NCS2* mutation leads to increased thiolation at body temperature. NCS2* yeast exhibits enhanced fitness when grown at elevated temperatures or when exposed to oxidative stress, inhibition of nutrient signalling, and cell-wall stress. Importantly, Ncs2* alters the interaction and stability of the thiolase complex likely mediated by nucleotide binding. The absence of 2-thiolation abrogates the in vivo virulence of pathogenic baker's yeast in infected mice. Finally, hypomodification triggers changes in colony morphology and hyphae formation in the common commensal pathogen Candida albicans resulting in decreased virulence in a human cell culture model. These findings demonstrate that 2-thiolation of tRNA acts as a key mediator of fungal virulence and reveal new mechanistic insights into the function of the highly conserved tRNA-thiolase complex.

Performance of a Large Language Model on Practice Questions for the Neonatal Board Examination.

This Diagnostic/Prognostic Study evaluates the performance of a large language model in generating answers to practice questions for the neonatal-perinatal board examination.

Deep learning-based left ventricular segmentation demonstrates improved performance on respiratory motion-resolved whole-heart reconstructions.

Introduction: Deep learning (DL)-based segmentation has gained popularity for routine cardiac magnetic resonance (CMR) image analysis and in particular, delineation of left ventricular (LV) borders for LV volume determination. Free-breathing, self-navigated, whole-heart CMR exams provide high-resolution, isotropic coverage of the heart for assessment of cardiac anatomy including LV volume. The combination of whole-heart free-breathing CMR and DL-based LV segmentation has the potential to streamline the acquisition and analysis of clinical CMR exams. The purpose of this study was to compare the performance of a DL-based automatic LV segmentation network trained primarily on computed tomography (CT) images in two whole-heart CMR reconstruction methods: (1) an in-line respiratory motion-corrected (Mcorr) reconstruction and (2) an off-line, compressed sensing-based, multi-volume respiratory motion-resolved (Mres) reconstruction. Given that Mres images were shown to have greater image quality in previous studies than Mcorr images, we hypothesized that the LV volumes segmented from Mres images are closer to the manual expert-traced left ventricular endocardial border than the Mcorr images. Method: This retrospective study used 15 patients who underwent clinically indicated 1.5 T CMR exams with a prototype ECG-gated 3D radial phyllotaxis balanced steady state free precession (bSSFP) sequence. For each reconstruction method, the absolute volume difference (AVD) of the automatically and manually segmented LV volumes was used as the primary quantity to investigate whether 3D DL-based LV segmentation generalized better on Mcorr or Mres 3D whole-heart images. Additionally, we assessed the 3D Dice similarity coefficient between the manual and automatic LV masks of each reconstructed 3D whole-heart image and the sharpness of the LV myocardium-blood pool interface. A two-tail paired Student's t-test (alpha = 0.05) was used to test the significance in this study. Results & Discussion: The AVD in the respiratory Mres reconstruction was lower than the AVD in the respiratory Mcorr reconstruction: 7.73 ± 6.54 ml vs. 20.0 ± 22.4 ml, respectively (n = 15, p-value = 0.03). The 3D Dice coefficient between the DL-segmented masks and the manually segmented masks was higher for Mres images than for Mcorr images: 0.90 ± 0.02 vs. 0.87 ± 0.03 respectively, with a p-value = 0.02. Sharpness on Mres images was higher than on Mcorr images: 0.15 ± 0.05 vs. 0.12 ± 0.04, respectively, with a p-value of 0.014 (n = 15). Conclusion: We conclude that the DL-based 3D automatic LV segmentation network trained on CT images and fine-tuned on MR images generalized better on Mres images than on Mcorr images for quantifying LV volumes.

Virological and cytological changes in tears and conjunctiva of patients with COVID-19.

Purpose: To analyze the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears/conjunctival epithelium and assess the cytomorphological changes in the conjunctival epithelium of coronavirus disease 2019 (COVID-19) patients. Methods: In this pilot study, patients with moderate to severe COVID-19 were recruited from the COVID ward/intensive care unit of the institute. Tears and conjunctival swabs were collected from COVID-19 patients and sent to the virology laboratory for reverse transcription polymerase chain reaction (RT-PCR) testing. Conjunctival swabs were used to prepare smears, which underwent cytological evaluation and immunocytochemistry for SARS-CoV-2 nucleocapsid protein. Results: Forty-two patients were included. The mean age of participants was 48.61 (range: 5-75) years. Seven (16.6%) patients tested positive for SARS-CoV-2 ribonucleic acid in tears samples, four (9.5%) of which were positive on conjunctival swab by RT-PCR in the first test. Cytomorphological changes were observed significantly more in smears from patients with positive RT-PCR on tear samples, including bi-/multi-nucleation (p = 0.01), chromatin clearing (p = 0.02), and intra-nuclear inclusions (p < 0.001). One case (3.2%) showed immunopositivity for SARS-CoV-2; this patient had severe disease and the lowest Ct values for tear and conjunctival samples among all positive cases. Conclusion: Conjunctival smears from patients with COVID-19 revealed cytomorphological alterations, even in the absence of clinically significant ocular infection. However, viral proteins were demonstrated within epithelial cells only rarely, suggesting that although the conjunctival epithelium may serve as a portal for entry, viral replication is possibly rare or short-lived.

Prognostic impact of artificial intelligence-based fully automated global circumferential strain in patients undergoing stress CMR.

AIMS: To determine whether fully automated artificial intelligence-based global circumferential strain (GCS) assessed during vasodilator stress cardiovascular (CV) magnetic resonance (CMR) can provide incremental prognostic value. METHODS AND RESULTS: Between 2016 and 2018, a longitudinal study included all consecutive patients with abnormal stress CMR defined by the presence of inducible ischaemia and/or late gadolinium enhancement. Control subjects with normal stress CMR were selected using a propensity score-matching. Stress-GCS was assessed using a fully automatic machine-learning algorithm based on featured-tracking imaging from short-axis cine images. The primary outcome was the occurrence of major adverse clinical events (MACE) defined as CV mortality or nonfatal myocardial infarction. Cox regressions evaluated the association between stress-GCS and the primary outcome after adjustment for traditional prognosticators. In 2152 patients [66 ± 12 years, 77% men, 1:1 matched patients (1076 with normal and 1076 with abnormal CMR)], stress-GCS was associated with MACE [median follow-up 5.2 (4.8-5.5) years] after adjustment for risk factors in the propensity-matched population [adjusted hazard ratio (HR), 1.12 (95% CI, 1.06-1.18)], and patients with normal CMR [adjusted HR, 1.35 (95% CI, 1.19-1.53), both P < 0.001], but not in patients with abnormal CMR (P = 0.058). In patients with normal CMR, an increased stress-GCS showed the best improvement in model discrimination and reclassification above traditional and stress CMR findings (C-statistic improvement: 0.14; NRI = 0.430; IDI = 0.089, all P < 0.001; LR-test P < 0.001). CONCLUSION: Stress-GCS is not a predictor of MACE in patients with ischaemia, but has an incremental prognostic value in those with a normal CMR although the absolute event rate remains low.

AI-Based Fully Automated Left Atrioventricular Coupling Index as a Prognostic Marker in Patients Undergoing Stress CMR.

BACKGROUND: The left atrioventricular coupling index (LACI) is a strong and independent predictor of heart failure (HF) in individuals without clinical cardiovascular disease. Its prognostic value is not established in patients with cardiovascular disease. OBJECTIVES: This study sought to determine in patients undergoing stress cardiac magnetic resonance (CMR) whether fully automated artificial intelligence-based LACI can provide incremental prognostic value to predict HF. METHODS: Between 2016 and 2018, the authors conducted a longitudinal study including all consecutive patients with abnormal (inducible ischemia or late gadolinium enhancement) vasodilator stress CMR. Control subjects with normal stress CMR were selected using propensity score matching. LACI was defined as the ratio of left atrial to left ventricular end-diastolic volumes. The primary outcome included hospitalization for acute HF or cardiovascular death. Cox regression was used to evaluate the association of LACI with the primary outcome after adjustment for traditional risk factors. RESULTS: In 2,134 patients (65 ± 12 years, 77% men, 1:1 matched patients [1,067 with normal and 1,067 with abnormal CMR]), LACI was positively associated with the primary outcome (median follow-up: 5.2 years [IQR: 4.8-5.5 years]) before and after adjustment for risk factors in the overall propensity-matched population (adjusted HR: 1.18 [95% CI: 1.13-1.24]), in patients with abnormal CMR (adjusted HR per 0.1% increment: 1.22 [95% CI: 1.14-1.30]), and in patients with normal CMR (adjusted HR per 0.1% increment: 1.12 [95% CI: 1.05-1.20]) (all P < 0.001). After adjustment, a higher LACI of ≥25% showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-index improvement: 0.16; net reclassification improvement = 0.388; integrative discrimination index = 0.153, all P < 0.001; likelihood ratio test P < 0.001). CONCLUSIONS: LACI is independently associated with hospitalization for HF and cardiovascular death in patients undergoing stress CMR, with an incremental prognostic value over traditional risk factors including inducible ischemia and late gadolinium enhancement.