Metabolic profiling of aortic stenosis and hypertrophic cardiomyopathy identifies mechanistic contrasts in substrate utilization.

Aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM) are distinct disorders leading to left ventricular hypertrophy (LVH), but whether cardiac metabolism substantially differs between these in humans remains to be elucidated. We undertook an invasive (aortic root, coronary sinus) metabolic profiling in patients with severe AS and HCM in comparison with non-LVH controls to investigate cardiac fuel selection and metabolic remodeling. These patients were assessed under different physiological states (at rest, during stress induced by pacing). The identified changes in the metabolome were further validated by metabolomic and orthogonal transcriptomic analysis, in separately recruited patient cohorts. We identified a highly discriminant metabolomic signature in severe AS in all samples, regardless of sampling site, characterized by striking accumulation of long-chain acylcarnitines, intermediates of fatty acid transport across the inner mitochondrial membrane, and validated this in a separate cohort. Mechanistically, we identify a downregulation in the PPAR-α transcriptional network, including expression of genes regulating fatty acid oxidation (FAO). In silico modeling of ß-oxidation demonstrated that flux could be inhibited by both the accumulation of fatty acids as a substrate for mitochondria and the accumulation of medium-chain carnitines which induce competitive inhibition of the acyl-CoA dehydrogenases. We present a comprehensive analysis of changes in the metabolic pathways (transcriptome to metabolome) in severe AS, and its comparison to HCM. Our results demonstrate a progressive impairment of ß-oxidation from HCM to AS, particularly for FAO of long-chain fatty acids, and that the PPAR-α signaling network may be a specific metabolic therapeutic target in AS.

Integrative Proteomic Analysis Reveals the Cytoskeleton Regulation and Mitophagy Difference Between Ischemic Cardiomyopathy and Dilated Cardiomyopathy.

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two primary etiologies of end-stage heart failure. However, there remains a dearth of comprehensive understanding the global perspective and the dynamics of the proteome and phosphoproteome in ICM and DCM, which hinders the profound comprehension of pivotal biological characteristics as well as differences in signal transduction activation mechanisms between these two major types of heart failure. We conducted high-throughput quantification proteomics and phosphoproteomics analysis of clinical heart tissues with ICM or DCM, which provided us the system-wide molecular insights into pathogenesis of clinical heart failure in both ICM and DCM. Both protein and phosphorylation expression levels exhibit distinct separation between heart failure and normal control heart tissues, highlighting the prominent characteristics of ICM and DCM. By integrating with omics results, Western blots, phosphosite-specific mutation, chemical intervention, and immunofluorescence validation, we found a significant activation of the PRKACA-GSK3ß signaling pathway in ICM. This signaling pathway influenced remolding of the microtubule network and regulated the critical actin filaments in cardiac construction. Additionally, DCM exhibited significantly elevated mitochondria energy supply injury compared to ICM, which induced the ROCK1-vimentin signaling pathway activation and promoted mitophagy. Our study not only delineated the major distinguishing features between ICM and DCM but also revealed the crucial discrepancy in the mechanisms between ICM and DCM. This study facilitates a more profound comprehension of pathophysiologic heterogeneity between ICM and DCM and provides a novel perspective to assist in the discovery of potential therapeutic targets for different types of heart failure.

Stem cell-based therapy in cardiac repair after myocardial infarction: Promise, challenges, and future directions.

Stem cells represent an attractive resource for cardiac regeneration. However, the survival and function of transplanted stem cells is poor and remains a major challenge for the development of effective therapies. As two main cell types currently under investigation in heart repair, mesenchymal stromal cells (MSCs) indirectly support endogenous regenerative capacities after transplantation, while induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) functionally integrate into the damaged myocardium and directly contribute to the restoration of its pump function. These two cell types are exposed to a common microenvironment with many stressors in ischemic heart tissue. This review summarizes the research progress on the mechanisms and challenges of MSCs and iPSC-CMs in post-MI heart repair, introduces several randomized clinical trials with 3D-mapping-guided cell therapy, and outlines recent findings related to the factors that affect the survival and function of stem cells. We also discuss the future directions for optimization such as biomaterial utilization, cell combinations, and intravenous injection of engineered nucleus-free MSCs.

Data-Independent Acquisition Proteomics and N-Terminomics Methods Reveal Alterations in Mitochondrial Function and Metabolism in Ischemic-Reperfused Hearts.

Myocardial ischemia-reperfusion (IR) (stunning) injury triggers changes in the proteome and degradome of the heart. Here, we utilize quantitative proteomics and comprehensive degradomics to investigate the molecular mechanisms of IR injury in isolated rat hearts. The control group underwent aerobic perfusion, while the IR injury group underwent 20 min of ischemia and 30 min of reperfusion to induce a stunning injury. As MMP-2 activation has been shown to contribute to myocardial injury, hearts also underwent IR injury with ARP-100, an MMP-2-preferring inhibitor, to dissect the contribution of MMP-2 to IR injury. Using data-independent acquisition (DIA) and mass spectroscopy, we quantified 4468 proteins in ventricular extracts, whereby 447 proteins showed significant alterations among the three groups. We then used subtiligase-mediated N-terminomic labeling to identify more than a hundred specific cleavage sites. Among these protease substrates, 15 were identified following IR injury. We identified alterations in numerous proteins involved in mitochondrial function and metabolism following IR injury. Our findings provide valuable insights into the biochemical mechanisms of myocardial IR injury, suggesting alterations in reactive oxygen/nitrogen species handling and generation, fatty acid metabolism, mitochondrial function and metabolism, and cardiomyocyte contraction.

Improved Cardiac Function in Postischemic Rats Using an Optimized Cardiac Reprogramming Cocktail Delivered in a Single Novel Adeno-Associated Virus.

BACKGROUND: Cardiac reprogramming is a technique to directly convert nonmyocytes into myocardial cells using genes or small molecules. This intervention provides functional benefit to the rodent heart when delivered at the time of myocardial infarction or activated transgenically up to 4 weeks after myocardial infarction. Yet, several hurdles have prevented the advancement of cardiac reprogramming for clinical use. METHODS: Through a combination of screening and rational design, we identified a cardiac reprogramming cocktail that can be encoded in a single adeno-associated virus. We also created a novel adeno-associated virus capsid that can transduce cardiac fibroblasts more efficiently than available parental serotypes by mutating posttranslationally modified capsid residues. Because a constitutive promoter was needed to drive high expression of these cell fate-altering reprogramming factors, we included binding sites to a cardiomyocyte-restricted microRNA within the 3' untranslated region of the expression cassette that limits expression to nonmyocytes. After optimizing this expression cassette to reprogram human cardiac fibroblasts into induced cardiomyocyte-like cells in vitro, we also tested the ability of this capsid/cassette combination to confer functional benefit in acute mouse myocardial infarction and chronic rat myocardial infarction models. RESULTS: We demonstrated sustained, dose-dependent improvement in cardiac function when treating a rat model 2 weeks after myocardial infarction, showing that cardiac reprogramming, when delivered in a single, clinically relevant adeno-associated virus vector, can support functional improvement in the postremodeled heart. This benefit was not observed with GFP (green fluorescent protein) or a hepatocyte reprogramming cocktail and was achieved even in the presence of immunosuppression, supporting myocyte formation as the underlying mechanism. CONCLUSIONS: Collectively, these results advance the application of cardiac reprogramming gene therapy as a viable therapeutic approach to treat chronic heart failure resulting from ischemic injury.

Effect of Electronic Nudges on Influenza Vaccination Rate in Older Adults With Cardiovascular Disease: Prespecified Analysis of the NUDGE-FLU Trial.

BACKGROUND: Influenza vaccines have been demonstrated to effectively reduce the incidence of influenza infection and potentially associated risks of cardiovascular events in patients with cardiovascular disease (CVD). Despite strong guideline and public health endorsements, global influenza vaccination rates in patients with CVD are highly variable. This prespecified analysis of NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) examined the effect of digital behavioral nudges on influenza vaccine uptake based on the presence of CVD. METHODS: NUDGE-FLU was a randomized, pragmatic, nationwide, register-based trial that included Danish citizens 65 years of age or older during the 2022 to 2023 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 electronic letters with designs based on behavioral concepts. Danish nationwide registers were used to collect baseline and outcome data. The primary end point was receipt of an influenza vaccine on or before January 1, 2023. The effects of the intervention letters were examined according to the presence of CVD and across cardiovascular subgroups that included heart failure, ischemic heart disease, and atrial fibrillation. RESULTS: Of 964 870 NUDGE-FLU participants from 691 820 households, 264 392 (27.4%) had CVD. During follow-up, 83.1% of participants with CVD versus 79.2% of participants without CVD received an influenza vaccination (P<0.001). Compared with usual care, a letter emphasizing the potential cardiovascular benefits of influenza vaccination increased vaccination rates; this effect was consistent in participants with CVD (absolute difference, +0.60 percentage points [99.55% CI, -0.48 to 1.68]) and without CVD (+0.98 percentage points [99.55% CI, 0.27-1.70; P for interaction=0.41). A repeated letter strategy with a reminder follow-up letter 14 days later was also effective in increasing influenza vaccination, irrespective of CVD (CVD: absolute difference, +0.80 percentage points [99.55% CI, -0.27 to 1.86]; no CVD: +0.67 percentage points [99.55% CI, -0.06 to 1.40]; P for interaction=0.77). Effectiveness of both nudging strategies was consistent across all major CVD subgroups. None of the other 7 nudging strategies were effective, regardless of CVD status. CONCLUSIONS: Electronic letter interventions emphasizing the potential cardiovascular benefits of influenza vaccination and using a reminder letter strategy were similarly beneficial in increasing influenza vaccination rates among older adults with and without CVD and across cardiovascular subgroups. Electronic nudges may improve influenza vaccine uptake in individuals with CVD. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05542004.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Cardiovascular Effects of Particulate Air Pollution.

Inhalation of fine particulate matter (PM2.5), produced by the combustion of fossil fuels, is an important risk factor for cardiovascular disease. Exposure to PM2.5 has been linked to increases in blood pressure, thrombosis, and insulin resistance. It also induces vascular injury and accelerates atherogenesis. Results from animal models corroborate epidemiological evidence and suggest that the cardiovascular effects of PM2.5 may be attributable, in part, to oxidative stress, inflammation, and the activation of the autonomic nervous system. Although the underlying mechanisms remain unclear, there is robust evidence that long-term exposure to PM2.5 is associated with premature mortality due to heart failure, stoke, and ischemic heart disease.

Comparative analysis of atherosclerotic cardiovascular disease burden between ages 20-54 and over 55 years: insights from the Global Burden of Disease Study 2019.

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

Ischemic cardiomyopathy: epidemiology, pathophysiology, outcomes, and therapeutic options.

Ischemic cardiomyopathy (ICM) is the most prevalent cause of heart failure (HF) in developed countries, with significant morbidity and mortality, despite constant improvements in the management of coronary artery disease. Current literature on this topic remains fragmented. Therefore, this review aimed to summarize the most recent data on ICM, focusing on its definition, epidemiology, outcomes, and therapeutic options. The most widely accepted definition is represented by a left ventricular dysfunction in the presence of significant coronary artery disease. The prevalence of ICM is largely influenced by age and sex, with older individuals and males being more affected. Its pathophysiology is characterized by plaque buildup, thrombus formation, hypoperfusion, ischemic cell death, and left ventricular remodeling. Despite improvements in therapy, ICM still represents a public health burden, with a 1-year mortality rate of 16% and a 5-year mortality rate of approximately 40% in the USA and Europe. Therefore, optimization of cardiovascular function, prevention of progressive remodeling, reduction of HF symptoms, and improved survival are the main goals of treatment. Therapeutic options for ICM include lifestyle changes, optimal medical therapy, revascularization, device therapy, mechanical circulatory support, and cardiac transplantation. Personalized management strategies and tailored patient care are needed to improve the outcomes of patients with ICM.

Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: There is a paucity of contemporary data on the prevalence and prognostic significance of cardiac autonomic neuropathy (CAN) from community-based cohorts with type 2 diabetes assessed using gold standard methods. The aim of this study was to assess these aspects of CAN in the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). METHODS: FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variation during deep breathing, Valsalva manoeuvre and standing. CAN (no/possible/definite) was assessed from the number of abnormal CARTs. Multinomial regression identified independent associates of CAN status. Cox proportional hazards modelling determined independent baseline predictors of incident heart failure (HF) and ischaemic heart disease (IHD), and all-cause mortality. RESULTS: Of 1254 participants assessed for CAN, 86 (6.9%) were outside CART age reference ranges and valid CART data were unavailable for 338 (27.0%). Of the remaining 830 (mean age 62.3 years, 55.3% males, median diabetes duration 7.3 years), 51.0%, 33.7% and 15.3% had no, possible or definite CAN, respectively. Independent associates of definite CAN (longer diabetes duration, higher body mass index and resting pulse rate, antidepressant and antihypertensive therapies, albuminuria, distal sensory polyneuropathy, prior HF) were consistent with those reported previously. In Kaplan-Meier analysis, definite CAN was associated with a lower likelihood of incident IHD and HF versus no/possible CAN (P < 0.001) and there was a graded increase in all-cause mortality risk from no CAN to possible and definite CAN (P < 0.001). When CAN category was added to the most parsimonious models, it was not a significant independent predictor of IHD (P ≥ 0.851) or HF (P ≥ 0.342). Possible CAN (hazard ratio (95% CI) 1.47 (1.01, 2.14), P = 0.046) and definite CAN (2.42 (1.60, 3.67), P < 0.001) increased the risk of all-cause mortality versus no CAN. CONCLUSIONS: Routine screening for CAN in type 2 diabetes has limited clinical but some prognostic value.

Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

BACKGROUND: Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. METHODS: We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. RESULTS: We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction = 0.038). CONCLUSIONS: A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Psychological Health and Ischemic Heart Disease in Women: A Review of Current Evidence and Clinical Considerations across the Healthspan.

PURPOSE OF REVIEW: Psychological health encompasses a constellation of negative and positive factors-i.e., psychosocial stress, depression, anxiety, trauma, loneliness and social isolation, anger and hostility, optimism, and a sense of purpose. This narrative review presents current evidence at the intersection of psychological health, risk of ischemic heart disease (IHD), and IHD-related outcomes, with an emphasis on associations in women. RECENT FINDINGS: For women, relations between psychological health and IHD reflect important sex and gender differences in biological and psychosocial factors. Although efforts devoted to understanding psychological health and IHD risk have varied by psychological factor-scientific evidence is strongest for psychosocial stress and depression, while anxiety, trauma, and positive psychological factors warrant more investigation-less optimal psychological health is consistently associated with an earlier and greater risk of IHD morbidity and mortality in women. Still, many past prospective studies of psychological factors and IHD risk had a limited representation of women, did not include analyses by sex, or failed to account for other influential, sex-specific factors. Thus, there are multiple pathways for further, rigorous investigation into psychological health-IHD associations, mechanisms, and empirically supported psychological interventions to mitigate IHD risk among women. Given the robust evidence linking psychological health with women's risk for IHD, implementing routine, brief, psychological screening is recommended. Significant life events, developmental milestones specific to women, and IHD diagnoses or events could cue further psychological assessment and referral, efforts which will mutually strengthen the evidence for integrated psychological and IHD care and delivery of such care to this vulnerable group.

Long-term survival of ischemic cardiomyopathy patients with severe left ventricular dysfunction after CABG vs heart transplantation: A single center retrospective analysis.

BACKGROUND: There are no guidelines on the surgical management for ischemic cardiomyopathy (ICM) patients with severe left ventricular dysfunction. The present study aims to assess the long-term survival of these patients treated with two different surgical techniques, coronary artery bypass grafting (CABG) and heart transplantation (HTx). METHODS: This retrospective study included 218 ICM patients with left ventricular ejection fraction (LVEF) ≤35% who underwent CABG (n = 106) and HTx (n = 112) from 2011 to 2021 in a single center. After propensity adjustment analysis each group consisted of 51 patients. Clinical characteristics were evaluated for all-cause follow-up mortality by the Cox proportional hazards regression model. A risk prediction model was generated from multivariable-adjusted Cox regression analysis and applied to stratify patients with different clinical risks. The long-term survival was estimated by Kaplan-Meier analysis for different surgery groups. RESULTS: Long-term survival was comparable between CABG and HTx groups. After being stratified into different risk subgroups according to risk predictors, the HTx group exhibited superior survival outcomes compared to the CABG group among the high-risk patients (67.8% vs 44.4%, 64.1% vs 38.9%, and 64.1% vs 33.3%, p = 0.047) at 12, 36, and 60 months respectively, while the survival was comparable between HTx and CABG groups among low-risk patients (87.0% vs 97.0%, 82.4% vs 97.0%, and 70.2% vs 91.6%, p = 0.11) at 12, 36, and 60 months respectively in the PSM cohort. CONCLUSION: Long-term survival in ICM patients with severe left ventricular dysfunction who received CABG or HTx was comparable in general. Nonetheless, a favorable outcome of HTx surgery compared to CABG was observed among high-risk patients.

Interference with GPR4 inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate oxygen-glucose deprivation/reoxygenation-induced inflammation and apoptosis of cardiomyocytes.

Myocardial ischemia/reperfusion (MI/R) injury is a detrimental disease with high mortality worldwide. We aimed to explore the role of G protein-coupled receptor 4 (GPR4) and lysophosphatidic acid receptor 1 (LPAR1) in MI/R injury in vitro. H9c2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to simulate the MI/R injury and GPR4 expression was detected. Then, GPR4 was knocked down and cell viability was examined with a CCK-8 assay. The activities of LDH, CK and CK-MB were detected to evaluate the damage of OGD/R-induced H9c2 cells. ELISA kits and TUNEL staining were used to examine the inflammation and apoptosis of H9c2 cells exposed to OGD/R conditions. Western blot was employed to detect the expression of proteins related to apoptosis and NLRP3 inflammasome signaling. Additionally, Co-IP analyzed the binding between GPR4 and LPAR1. Finally, LPAR1 was overexpressed to conduct the rescue experiments. Results revealed that GPR4 was upregulated in OGD/R-treated H9c2 cells and GPR4 knockdown attenuated the damage of H9c2 cells. OGD/R induced inflammation and apoptosis were markedly inhibited by GPR4 silencing, as evidenced by the decreased TNF-α, IL-6 and IL-8 levels as well as the elevated Bcl-2 expression and reduced Bax and cleaved caspase3 expression. Moreover, GPR4 bound to LPAR1 and upregulated LPAR1 expression. Interference with GPR4 inactivated the NLRP3 inflammasome signaling. Besides, LPAR1 overexpression abrogated the effects of GPR4 silencing on the damage, inflammation and apoptosis of H9c2 cells induced by OGD/R. Particularly, LPAR1 upregulation promoted the activation of NLRP3 inflammasome signaling in GPR4-silenced H9c2 cells induced by OGD/R. To be concluded, GPR4 deficiency inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate OGD/R -induced inflammation and apoptosis of cardiomyocytes.

Competency based curriculum for cardiovascular magnetic resonance: A position statement of the Society for Cardiovascular Magnetic Resonance.

This position statement guides cardiovascular magnetic resonance (CMR) imaging program directors and learners on the key competencies required for Level II and III CMR practitioners, whether trainees come from a radiology or cardiology background. This document is built upon existing curricula and was created and vetted by an international panel of cardiologists and radiologists on behalf of the Society for Cardiovascular Magnetic Resonance (SCMR).

Improved Robustness for Deep Learning-based Segmentation of Multi-Center Myocardial Perfusion MRI Datasets Using Data Adaptive Uncertainty-guided Space-time Analysis.

BACKGROUND: Fully automatic analysis of myocardial perfusion MRI datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge. METHODS: Datasets from 3 medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models against differences in pulse sequence (exD-1) and scanner vendor (exD-2). A subset of inD (n = 85) was used for training/validation of a pool of DNNs for segmentation, all using the same spatiotemporal U-Net architecture and hyperparameters but with different parameter initializations. We employed a space-time sliding-patch analysis approach that automatically yields a pixel-wise "uncertainty map" as a byproduct of the segmentation process. In our approach, dubbed Data Adaptive Uncertainty-Guided Space-time (DAUGS) analysis, a given test case is segmented by all members of the DNN pool and the resulting uncertainty maps are leveraged to automatically select the "best" one among the pool of solutions. For comparison, we also trained a DNN using the established approach with the same settings (hyperparameters, data augmentation, etc.). RESULTS: The proposed DAUGS analysis approach performed similarly to the established approach on the internal dataset (Dice score for the testing subset of inD: 0.896 ± 0.050 vs. 0.890 ± 0.049; p = n.s.) whereas it significantly outperformed on the external datasets (Dice for exD-1: 0.885 ± 0.040 vs. 0.849 ± 0.065, p < 0.005; Dice for exD-2: 0.811 ± 0.070 vs. 0.728 ± 0.149, p < 0.005). Moreover, the number of image series with "failed" segmentation (defined as having myocardial contours that include bloodpool or are noncontiguous in ≥1 segment) was significantly lower for the proposed vs. the established approach (4.3% vs. 17.1%, p < 0.0005). CONCLUSIONS: The proposed DAUGS analysis approach has the potential to improve the robustness of deep learning methods for segmentation of multi-center stress perfusion datasets with variations in the choice of pulse sequence, site location or scanner vendor.

Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET.

BACKGROUND: Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). METHODS: Thirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. RESULTS: The results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (-0.93 to 0.84 ml/g/min). CONCLUSIONS: Agreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

Prospective Comparison of Free-Breathing Accelerated Cine Deep Learning Reconstruction Versus Standard Breath-Hold Cardiac MRI Sequences in Patients With Ischemic Heart Disease.

BACKGROUND. Cine cardiac MRI sequences require repeated breath-holds, which can be difficult for patients with ischemic heart disease (IHD). OBJECTIVE. The purpose of the study was to compare a free-breathing accelerated cine sequence using deep learning (DL) reconstruction and a standard breath-hold cine sequence in terms of image quality and left ventricular (LV) measurements in patients with IHD undergoing cardiac MRI. METHODS. This prospective study included patients undergoing 1.5- or 3-T cardiac MRI for evaluation of IHD between March 15, 2023, and June 21, 2023. Examinations included an investigational free-breathing cine short-axis sequence with DL reconstruction (hereafter, cine-DL sequence). Two radiologists (reader 1 [R1] and reader 2 [R2]), in blinded fashion, independently assessed left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and subjective image quality for the cine-DL sequence and a standard breath-hold balanced SSFP sequence; R1 assessed artifacts. RESULTS. The analysis included 26 patients (mean age, 64.3 ± 11.7 [SD] years; 14 men, 12 women). Acquisition was shorter for the cine-DL sequence than the standard sequence (mean ± SD, 0.6 ± 0.1 vs 2.4 ± 0.6 minutes; p < .001). The cine-DL sequence, in comparison with the standard sequence, showed no significant difference for LVEF for R1 (mean ± SD, 51.7% ± 14.3% vs 51.3% ± 14.7%; p = .56) or R2 (53.4% ± 14.9% vs 52.8% ± 14.6%; p = .53); significantly greater LVEDV for R2 (mean ± SD, 171.9 ± 51.9 vs 160.6 ± 49.4 mL; p = .01) but not R1 (171.8 ± 53.7 vs 165.5 ± 52.4 mL; p = .16); and no significant difference in LVESV for R1 (mean ± SD, 88.1 ± 49.3 vs 86.0 ± 50.5 mL; p = .45) or R2 (85.2 ± 48.1 vs 81.3 ± 48.2 mL; p = .10). The mean bias between the cine-DL and standard sequences by LV measurement was as follows: LVEF, 0.4% for R1 and 0.7% for R2; LVEDV, 6.3 mL for R1 and 11.3 mL for R2; and LVESV, 2.1 mL for R1 and 3.9 mL for R2. Subjective image quality was better for cine-DL sequence than the standard sequence for R1 (mean ± SD, 2.3 ± 0.5 vs 1.9 ± 0.8; p = .02) and R2 (2.2 ± 0.4 vs 1.9 ± 0.7; p = .02). R1 reported no significant difference between the cine-DL and standard sequences for off-resonance artifacts (3.8% vs 23.1% examinations; p = .10) and parallel imaging artifacts (3.8% vs 19.2%; p = .19); blurring artifacts were more frequent for the cine-DL sequence than the standard sequence (42.3% vs 7.7% examinations; p = .008). CONCLUSION. A free-breathing cine-DL sequence, in comparison with a standard breath-hold cine sequence, showed very small bias for LVEF measurements and better subjective quality. The cine-DL sequence yielded greater LV volumes than the standard sequence. CLINICAL IMPACT. A free-breathing cine-DL sequence may yield reliable LVEF measurements in patients with IHD unable to repeatedly breath-hold. TRIAL REGISTRATION. ClinicalTrials.gov NCT05105984.

Cost prediction for ischemic heart disease hospitalization: Interpretable feature extraction using network analysis.

OBJECTIVES: Ischemic heart disease (IHD) is a significant contributor to global mortality and disability, imposing a substantial social and economic burden on individuals and healthcare systems. To enhance the efficient allocation of medical resources and ultimately benefit a larger population, accurate prediction of healthcare costs is crucial. METHODS: We developed an interpretable IHD hospitalization cost prediction model that integrates network analysis with machine learning. Specifically, our network-enhanced model extracts explainable features by leveraging a diagnosis-procedure concurrence network and advanced graph kernel techniques, facilitating the capture of intricate relationships between medical codes. RESULTS: The proposed model achieved an R2 of 0.804 ± 0.008 and a root mean square error (RMSE) of 17,076 ± 420 CNY on the temporal validation dataset, demonstrating comparable performance to the model employing less interpretable code embedding features (R2: 0.800 ± 0.008; RMSE: 17,279 ± 437 CNY) and the hybrid graph isomorphism network (R2: 0.802 ± 0.007; RMSE: 17,249 ± 387 CNY). The interpretation of the network-enhanced model assisted in pinpointing specific diagnoses and procedures associated with higher hospitalization costs, including acute kidney injury, permanent atrial fibrillation, intra-aortic balloon bump, and temporary pacemaker placement, among others. CONCLUSION: Our analysis results demonstrate that the proposed model strikes a balance between predictive accuracy and interpretability. It aids in identifying specific diagnoses and procedures associated with higher hospitalization costs, underscoring its potential to support intelligent management of IHD.