T-2 toxin induces cardiac fibrosis by causing metabolic disorders and up-regulating Sirt3/FoxO3α/MnSOD signaling pathway-mediated oxidative stress.

T-2 toxin, an omnipresent environmental contaminant, poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity. This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin. Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0, 10, and 100 nanograms per gram body weight per day (ng/(g·day)), respectively. Morphological, pathological, and ultrastructural alterations in cardiac tissue were meticulously examined. Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites. The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected. The results showed that exposure to T-2 toxin elicited myocardial tissue disorders, interstitial hemorrhage, capillary dilation, and fibrotic damage. Mitochondria were markedly impaired, including swelling, fusion, matrix degradation, and membrane damage. Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiac metabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway. T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress. In conclusion, the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway. This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.

Pediatric reference values of NT-proBNP and Galectin-3 based on a French cohort.

BACKGROUND: In pediatric cardiology, the fact that some new biomarkers have assay-specific normal values has to be considered for correct clinical decisions. The current study aimed to provide age-adjusted normative values for NT-proBNP and Galectin-3 using the Abbott immunoassay system from a prospective French pediatric cohort sera collection and to validate our data for NT-proBNP on a second retrospective cohort. METHODS: We analyzed 283 consecutive samples for NT-proBNP and 140 samples for Galectin-3 collected from apparently healthy children (0-18 years) with outpatient treatment at our institution (Hôpital Necker-Enfants malades, Paris, France) during 24 months. RESULTS: For NT-proBNP and Galectin-3, we establish four age partitions, respectively two (<2 years / >2 years) and establish upper reference values and their 90 % CI for each biomarker (Galectin-3 (ng/mL): 56 [44-70] / 26 [23-29]). We evaluated the diagnostic performance of our upper reference values of NT-proBNP on a retrospective cohort (n = 428) with positive predictive value of 0.92. CONCLUSIONS: Using Abbott immunoassay system, we report age-specific reference values for NT-proBNP and for the first time for Galectin-3 in a healthy French pediatric cohort. These data call for larger cohort studies to define more robustly percentiles and diagnostic performance for NT-proBNP.

Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Comparative evaluation of single and multiple exposure to PM2.5 in respirable air on cardiac physiology, structure and function in a Wistar rat model.

Many studies have shown the negative relationship between long term exposure to PM2.5 and cardiac dysfunction. Recently, studies have shown that even a single exposure of PM2.5 from air sample in permissible range can induce very mild cardiac pathological changes. In the present study, we revisited the toxic effect of PM2.5 on rat heart by adopting single and multiple exposure durations. Female Wistar rats were exposed to PM2.5 at a concentration of 250 µg/m3 daily for 3 hr for single (1 day) and multiple (7, 14, 21 days) durations. The major pathological changes noted in 21 days exposed myocardium comprised of an elevated ST segment (the segment between the S wave and the T wave), development of cardiac fibrosis, hypertrophy, cardiac injury, tissue inflammation and declined cardiac function. With 14 days exposed heart, the electrocardiograms (ECG),data showed insignificantly declined heart rate and an increased QT (the time from the start of the Q wave to the end of the T wave) interval along with mild fibrosis, hypertrophy and lesser number of TUNEL positive cells. On the other hand, single- and 7-days exposure to PM2.5 did not impart any significant changes in the myocardium. To determine the reversibility potential of PM2.5 induced cardiotoxicity, a washout period of 24 hours was adopted and all observed changes in the myocardium were reversed till day 7, but not in 14- and 21-days exposed samples. Based on the above findings we concluded that PM2.5 associated cardiac dysfunction is the cumulative outcome of ineffective cardiac adaptive and repair process that accumulate additively over the time due to prolonged exposure durations.

Características clínicas de reanimações cardiopulmonares intra-hospitalares registradas em prontuário: estudo transversal / Clinical characteristics of in-hospital cardiopulmonary resuscitations recorded in medical records: a cross-sectional study / Características clínicas de las reanimaciones cardiopulmonares intrahospitalarias registradas en las historias clínicas: estudio transversal

Objetivo: identificar características clínicas das paradas cardiopulmonares e reanimações cardiopulmonares ocorridas em ambiente intra-hospitalar. Método: estudo quantitativo, prospectivo e observacional, a partir de informações de prontuários de pacientes submetidos a manobras de reanimação devido à parada cardiopulmonar entre janeiro e dezembro de 2021. Utilizou-se um instrumento baseado nas variáveis do modelo de registro Utstein. Resultados: em 12 meses foram registradas 37 paradas cardiopulmonares. A maioria ocorreu na unidade de terapia intensiva respiratória, com causa clínica mais prevalente hipóxia. 65% dos pacientes foram intubados no atendimento e 57% apresentaram ritmo atividade elétrica sem pulso. A duração da reanimação variou entre menos de cinco a mais de 20 minutos. Como desfecho imediato, 57% sobreviveram. Conclusão: dentre os registros analisados, a maior ocorrência de paradas cardiopulmonares foi na unidade de terapia intensiva respiratória, relacionada à Covid-19. Foram encontrados registros incompletos e ausência de padronização nas condutas.

Objective: identify the clinical characteristics of cardiopulmonary arrests and cardiopulmonary resuscitations in the in-hospital environment. Method: this is a quantitative, prospective and observational study based on information from the medical records of patients who underwent resuscitation maneuvers due to cardiopulmonary arrest between January and December 2021. An instrument based on the variables of the Utstein registration protocol was used. Results: thirty-seven cardiopulmonary arrests were recorded in 12 months. The majority occurred in a respiratory intensive care unit, with hypoxia being the most prevalent clinical cause. Sixty-five percent of the patients were intubated and 57% had pulseless electrical activity. The duration of resuscitation ranged from less than five to more than 20 min. As for the immediate outcome, 57% survived. Conclusion: among the records analyzed, the highest occurrence of cardiopulmonary arrests was in respiratory intensive care units, and they were related to Covid-19. Moreover, incomplete records and a lack of standardization in cardiopulmonary resuscitation procedures were found.

Objetivo: Identificar las características clínicas de paros cardiopulmonares y reanimaciones cardiopulmonares que ocurren en un ambiente hospitalario. Método: estudio cuantitativo, prospectivo y observacional, realizado a partir de información presente en historias clínicas de pacientes sometidos a maniobras de reanimación por paro cardiorrespiratorio entre enero y diciembre de 2021. Se utilizó un instrumento basado en las variables del modelo de registro Utstein. Resultados: en 12 meses se registraron 37 paros cardiopulmonares. La mayoría ocurrió en la unidad de cuidados intensivos respiratorios, la causa clínica más prevalente fue la hipoxia. El 65% de los pacientes fue intubado durante la atención y el 57% presentaba un ritmo de actividad eléctrica sin pulso. La duración de la reanimación varió entre menos de cinco y más de 20 minutos. Como resultado inmediato, el 57% sobrevivió. Conclusión: entre los registros analizados, la mayor cantidad de paros cardiopulmonares se dio en la unidad de cuidados intensivos respiratorios, relacionada con Covid-19. Se encontraron registros incompletos y falta de estandarización en el procedimiento.

Austrian consensus statement on the diagnosis and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000-40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms.

Central versus peripheral VA ECMO for cardiogenic shock: an 8-year experience of a tertiary cardiac surgery center in Greece.

BACKGROUND: VA ECMO has emerged as an effective rescue therapy in patients with cardiogenic shock refractory to standard treatment protocols and its use is rising worldwide in the last decade. Although experience and availability are growing, outcomes remain poor. There is need for evidence to ameliorate clinical practice and improve outcomes. METHODS: We retrospectively reviewed the medical records of all patients who were supported with VA ECMO for cardiogenic shock at our institution between January 2015 and January 2023. The study purpose was to compare outcomes between patients who were supported with central versus peripheral configuration. RESULTS: ECMO was applied in 108 patients of whom central configuration in 48 (44%) and peripheral in 60 (56%). Patients supported with central VA ECMO were more likely to be supported for post cardiotomy shock [OR 4.6 (CI 95% 2.03 - 10.41)], while patients in the peripheral group for chronic heart failure decompensation [OR 9.4 (CI 95% 1.16 - 76.3]. Central VA ECMO had worse survival during ECMO support (29.2% vs 51.7%, p=0.018) and at discharge (8% vs 37%, p=0.001). These patients were at high risk of complications, such as acute kidney injury (AKI), [OR 2.37 (CI 95% 1.06 - 5.3), p = 0.034] and major bleeding [OR 3.08 (CI 95% 1.36 - 6.94), p<0.001]. CONCLUSIONS: Patients on central VA ECMO were supported mainly for post cardiotomy shock, presented with more complications such as major bleeding and AKI and had worse survival to hospital discharge, compared with patients on peripheral VA ECMO. Patient selection, timing of implementation, cannulation strategy and configuration remain main determinants of clinical outcome.

Multiscale Fiber Remodeling in the Infarcted Left Ventricle using a Stress-Based Reorientation Law.

The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI), this organization can become disrupted, leading to degraded pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs. The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future. STATEMENT OF SIGNIFICANCE: The organization of muscle and collagen fibers within the heart plays a significant role in defining cardiac function. This organization can become disrupted after a heart attack, leading to degraded pumping performance. In the current study, we implemented a stress-based fiber reorientation law into a computer model of the heart, which seeks to realign the fibers such that contractile force and load bearing capabilities are maximized. The primary goal was to evaluate the effects of different sized heart attacks. We observed substantial fiber remodeling in the heart, which matched experimental observations. The proposed computational framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.

Gender differences in cardiac rehabilitation participation and outcomes: an 18-year retrospective study in Iran.

BACKGROUND: Cardiac rehabilitation (CR) is crucial for addressing cardiovascular diseases globally, with a specific emphasis on gender differences. Despite its demonstrated benefits for women, there's limited acceptance globally, especially in low- and middle-income countries. The program aims to optimize risk factors and improve overall patient well-being. METHODS: A cohort study was performed on those who were candidates for CR programs during 2001-2019. Assessments were performed within one week before and one week after the 8-week CR program. Age, sex, smoking status, clinical data, resting systolic and diastolic blood pressure (SBP and DBP, respectively), echocardiography and laboratory data were obtained. Functional capacity was evaluated using the international physical activity questionnaire, and a treadmill exercise test. Anxiety, depression, general quality of life (QoL), and health-related QoL were selected for psychological status. Then statistical analysis was performed on data. RESULT: In this study, the number of male patients was 1526 (73.69%). The average age of patients in the female group was higher than that of males (58.66 ± 9.08 vs. 56.18 ± 9.94), according to the crude model results, the changes in emotional, social and physical scores were significant (P-value:0.028, 0.018, 0.030), as well as the differences in Mets and smoking were significant (P-value for both < 0.001) in the adjusted model, the emotional variables and Mets changes were significant in two groups, so that the emotional score in the female group was higher than that of the male group, and the female Mets score was significantly lower than that of the male group. CONCLUSION: The CR program can improve cardiovascular outcomes, but the greatest impact was on the quality of life, patient METs and smoking behavers. Also the number of female participants in the CR program was less than the number of males.

Pathophysiological dynamics of acute myocardial infarction rats under chronic psychological stress at different time points.

There is a lack of in-depth research on the impacts and changes in chronic psychological stress (CPS) on the cardiovascular system after acute myocardial infarction (AMI). This study aims to explore the comorbid mechanism and dynamic evolution of AMI exposed to CPS. 120 Wistar rats were randomly divided into Sham Operation group, Sham Operation + Chronic Unpredictable Mild Stress (CUMS) group, AMI group and AMI + CUMS group, with each group further divided into subgroups at days 7, 14, and 28. The AMI model was created by ligating the left anterior descending coronary artery, and CUMS model was used to induce CPS in rats. Behavioral changes were assessed through open field tests and sucrose preference tests. Cardiac function and structure were evaluated via echocardiography. The serum levels of TNFα, IL-6, NO, ET, CK-MB, cTNT, and ANP were measured using assay kits. Pathological changes in cardiac and brain tissues were observed under an optical microscope. Comparative analysis across different models revealed that CUMS significantly reduced behavioral activities in rats, with an interaction between CUMS and AMI affecting total distance (P < 0.05). Both CUMS and AMI significantly reduced cardiac function indicators, with their interaction effects on LVEF, LVFS, and CO (P < 0.05). AMI significantly altered cardiac structural parameters, particularly on day 28 (P < 0.05); while the impact of CUMS on cardiac structure was not significant, except for a notable reduction in LVAW/s on day 7 in AMI + CUMS group (P < 0.05). AMI caused significant changes in the serum biomarkers, while CUMS only significantly increased cTnT on day 7, ANP, TNFα, and IL-6 on day 14, and CK-MB on day 28, with their interaction effects on the three myocardial injury markers and TNFα (P < 0.05). Comparative analysis across different time points demonstrated that behavioral activity, cardiac function, CK-MB, cTnT, ANP, TNFα, and ET levels decreased significantly over time in the AMI model rats, while the left ventricular mass increased significantly (P < 0.05). Pathologically, compared with stress or AMI alone, the AMI + CUMS group exhibited more severe myocardia cellular degeneration and inflammatory infiltration, causing larger infract areas in myocardial tissue, as well as cell number decreases and morphological changes in hippocampal tissue. AMI with CPS exacerbates myocardial injury through sustained inflammation and endothelial dysfunction, leading to heart-brain pathology manifestations characterized by decreased cardiac function and hippocampal tissue damage.

Taurolidine-containing solution for reducing cardiac implantable electronic device infection-early report from the European TauroPace™ registry.

INTRODUCTION: Infection is a significant complication of cardiac implantable electronic device (CIED) therapy. The European TauroPace™ Registry investigates the safety and efficacy of TauroPace™ (TP), an antimicrobial solution containing taurolidine, designed to prevent CIED infections. METHODS: This multicenter study included patients undergoing CIED procedures at participating centers where TP was used as a disinfectant for external hardware surfaces and an antiseptic for irrigating surgical sites. All patients eligible for CIED placement with adjunctive TP as the standard of care were included. Other aspects of CIED procedures adhered to current guidelines. Data on CIED-related infective endocarditis, CIED pocket infection, device and procedure-related complications, adverse events, and all-cause mortality were prospectively collected for 12 months. In cases of revision, the previous procedure was censored, and a new procedure was created. Binomial and Kaplan-Meier statistics were employed to analyze event rates. RESULTS: From January 2020 to November 2022, TP was used in 822 out of 1170 CIED procedures. Among patients who completed the 3-month follow-up, no CIED pocket infections were observed, and one case of CIED-related infective endocarditis was reported. In the 12-month follow-up cohort, two additional local pocket CIED infections were observed, resulting in a total of three major CIED infections within 1 year after the CIED placement procedure. The 3-month and 12-month major CIED infection rates were 0.125% and 0.51%, respectively. During the observation a complication rate of 4.4% was reported. No adverse events related to TP were observed. CONCLUSIONS: TP appears to be effective and safe in preventing CIED infections. CLINICALTRIALS: gov Identifier: NCT04735666.

Speckle-tracking echocardiography as screening tool for myocardial fibrosis and Iron overload in transfusion-dependent beta-thalassemia.

BACKGROUND: Transfusion-dependent beta thalassemia (TDT) is a genetic disorder characterized by low haemoglobin levels, often leading to myocardial iron overload (MIO) and myocardial fibrosis (MF). Cardiac Magnetic Resonance (CMR) represents the gold standard for MIO and MF assessment, although its limited availability and high costs pose challenges. Left Ventricular Global Longitudinal Strain (LV GLS) measured by Speckle Tracking Echocardiography (STE) could offer a valuable alternative. METHODS: A monocentric diagnostic accuracy study was conducted to compare the performance of LV GLS with CMR using T2* for evaluating MIO and late gadolinium enhancement (LGE) for detecting MF. Between January 2022 and January 2023, 44 consecutive patients with TDT were enrolled. For each participant was performed LV GLS with STE, including CMR with T2* technique and LGE sequences. RESULTS: CMR identified MIO in 8 patients (18 %) and MF in 5 (11 %). LV GLS STE was normal in patients without MIO (-20.6 ±â€¯3.1 %) or MF (-20.6 ±â€¯2.8 %), significantly differing from those with MIO (-18.2 ±â€¯2.1 %, p = 0.043) and MF (-16.4 ±â€¯1.7 %, p = 0.002). ROC analysis indicated an optimal LV GLS STE cutoff of -19.8 % for MIO (AUC = 0.76, 95 % CI: 0.59-0.93, p = 0.054) with an overall diagnostic accuracy of 64 % and an optimal cutoff of -18.3 % for MF (AUC = 0.93, 95 % CI: 0.85-1.00, p = 0.009) with an accuracy of 86 %. CONCLUSIONS: The findings of this pilot study indicate that LV GLS with STE, may be a cost-effective screening tool for the early detection of MIO and MF in TDT patients.

Low physical activity level in out-of-hospital cardiac arrest survivors with obesity, mobility problems and cognitive impairment: Results from the TTM2 trial.

AIMS: To describe the level of physical activity 6 months after an out-of-hospital cardiac arrest (OHCA) and to explore potential risk factors of a low level of physical activity. METHODS: Post-hoc analyses of the international multicentre Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac arrest (TTM2) trial. At 6 months, survivors at 61 sites in Europe, Australia and New Zeeland were invited to a follow-up. The participants answered two questions on self-reported physical activity. Answers were categorized as a low, moderate, or high level of physical activity and further dichotomized into a low versus moderate/high level of physical activity. Potential risk factors for a low level of physical activity were collected and investigated by univariable and multivariable logistic regression. RESULTS: At 6 months, 807 of 939 (86%) OHCA survivors answered the two questions of physical activity; 34% reported a low, 44% moderate and 22% high level of physical activity. Obesity (OR=1.75, 95% CI 1.10-2.77, p=0.018), mobility problems by EuroQol 5 dimensions 5 levels (OR=1.73, 95% CI 1.06-2.84, p=0.029), and cognitive impairment by Symbol Digit Modalities Test (OR=1.78, 95% CI 1.13-2.82, p=0.013) were significantly associated with a low level of physical activity in the multivariable analysis. CONCLUSION: One third of the OHCA survivors reported a low level of physical activity. Obesity, mobility problems, and cognitive impairment were associated with a low level of physical activity. CLINICALTRIALS: gov Identifier: NCT02908308.

Detecting cardiac states with wearable photoplethysmograms and implications for out-of-hospital cardiac arrest detection.

Out-of-hospital cardiac arrest (OHCA) is a global health problem affecting approximately 4.4 million individuals yearly. OHCA has a poor survival rate, specifically when unwitnessed (accounting for up to 75% of cases). Rapid recognition can significantly improve OHCA survival, and consumer wearables with continuous cardiopulmonary monitoring capabilities hold potential to "witness" cardiac arrest and activate emergency services. In this study, we used an arterial occlusion model to simulate cardiac arrest and investigated the ability of infrared photoplethysmogram (PPG) sensors, often utilized in consumer wearable devices, to differentiate normal cardiac pulsation, pulseless cardiac (i.e., resembling a cardiac arrest), and non-physiologic (i.e., off-body) states. Across the classification models trained and evaluated on three anatomical locations, higher classification performances were observed on the finger (macro average F1-score of 0.964 on the fingertip and 0.954 on the finger base) compared to the wrist (macro average F1-score of 0.837). The wrist-based classification model, which was trained and evaluated using all PPG measurements, including both high- and low-quality recordings, achieved a macro average precision and recall of 0.922 and 0.800, respectively. This wrist-based model, which represents the most common form factor in consumer wearables, could only capture about 43.8% of pulseless events. However, models trained and tested exclusively on high-quality recordings achieved higher classification outcomes (macro average F1-score of 0.975 on the fingertip, 0.973 on the finger base, and 0.934 on the wrist). The fingertip model had the highest performance to differentiate arterial occlusion pulselessness from normal cardiac pulsation and off-body measurements with macro average precision and recall of 0.978 and 0.972, respectively. This model was able to identify 93.7% of pulseless states (i.e., resembling a cardiac arrest event), with a 0.4% false positive rate. All classification models relied on a combination of time-, power spectral density (PSD)-, and frequency-domain features to differentiate normal cardiac pulsation, pulseless cardiac, and off-body PPG recordings. However, our best model represented an idealized detection condition, relying on ensuring high-quality PPG data for training and evaluation of machine learning algorithms. While 90.7% of our PPG recordings from the fingertip were considered of high quality, only 53.2% of the measurements from the wrist passed the quality criteria. Our findings have implications for adapting consumer wearables to provide OHCA detection, involving advancements in hardware and software to ensure high-quality measurements in real-world settings, as well as development of wearables with form factors that enable high-quality PPG data acquisition more consistently. Given these improvements, we demonstrate that OHCA detection can feasibly be made available to anyone using PPG-based consumer wearables.

NLRX1 attenuates endoplasmic reticulum stress via STING in cardiac hypertrophy.

Endoplasmic reticulum stress-induced cell apoptosis is a pivotal mechanism underlying the progression of cardiac hypertrophy. NLRX1, a member of the NOD-like receptor family, modulates various cellular processes, including STING, NF-κB, MAPK pathways, reactive oxygen species production, essential metabolic pathways, autophagy and cell death. Emerging evidence suggests that NLRX1 may offer protection against diverse cardiac diseases. However, the impacts and mechanisms of NLRX1 on endoplasmic reticulum stress in cardiac hypertrophy remains largely unexplored. In our study, we observed that the NLRX1 and phosphorylated STING (p-STING) were highly expressed in both hypertrophic mouse heart and cellular model of cardiac hypertrophy. Whereas over-expression of NLRX1 mitigated the expression levels of p-STING, as well as the endoplasmic reticulum stress markers, including transcription activating factor 4 (ATF4), C/EBP homologous protein (CHOP) and the ratios of phosphorylated PERK to PERK, phosphorylated IRE1 to IRE1 and phosphorylated eIF2α to eIF2α in an Angiotensin II (Ang II)-induced cellular model of cardiac hypertrophy. Importantly, the protective effects of NLRX1 were attenuated upon pretreatment with the STING agonist, DMXAA. Our findings provide the evidence that NLRX1 attenuates the PERK-eIF2α-ATF4-CHOP axis of endoplasmic reticulum stress response via inhibition of p-STING in Ang II-treated cardiomyocytes, thereby ameliorating the development of cardiac hypertrophy.