SGLT-2i associated diabetic ketoacidosis in the setting of cardiogenic shock.

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. Sodium-glucose co-transport inhibitors (SGLT-2i), a treatment for type 2 diabetes, have demonstrated a survival benefit in patients with heart failure with reduced ejection fraction (HFrEF). Many patients with HFrEF have been started on SGLT-2i and sometimes transitioned off insulin due to improved glycaemic control. SGLT-2i have demonstrated an association with DKA. Here, we present a case of simultaneous cardiogenic shock and DKA in the setting of recent transition from insulin to an SGLT-2i. DKA in conjunction with decompensated heart failure is a combination that will likely occur more frequently as SGLT-2i use becomes more widespread in patients with HFrEF, and its identification and management require special considerations. Volume status, potassium management and recognition of DKA in these patients must be approached differently than in other cases of DKA.

Comparing flow and pulmonary artery growth post-patent ductus arteriosus stenting in patients with ductal-dependent pulmonary flow using 4D magnetic resonance imaging.

Aims: The 4D magnetic resonance imaging (4D-flow MRI) provides a qualitative and quantitative assessment of cardiovascular structures and processes. 4D-flow MRI was used to study pulmonary flow in post-patent ductus arteriosus (PDA) stent insertion in duct-dependent pulmonary flow neonates at baseline (PDA stent insertion) and after 6 months, and also, to evaluate the effect of flow dynamics on the growth of pulmonary arteries (PAs). Methods and results: This prospective observational study included neonates with ductus arteriosus-dependent pulmonary circulation who underwent ductal stenting between June 2021 and November 2022. Cardiac 4D-flow MRI and magnetic resonance angiography were conducted in two phases; after the deployment of the PDA stent during the neonatal period and after 6 months from stent deployment. Eight neonates were recruited, but only five completed both scans. A total of 10 PAs were evaluated during each phase. The median left PA (LPA) and right PA (RPA) diameters and indexed flow for LPA and RPA were evaluated. The growth rate of LPA was observed to be lower than that of RPA (percentage diameter increase: 74 vs. 153%). LPA Z-score was lower than RPA. Indexed flow in both LPA and RPA showed a reduction in the 6-month scan, which was consistent with reduced stent patency. Conclusion: 4D-flow cardiac MRI showed different growth rates and reduced flow between LPA and RPA post-PDA stent. These insights can aid in future management decisions.

The heart of plastic: utilizing the Drosophila model to investigate the effects of micro/nanoplastics on heart function.

Microplastics (MPs) and nanoplastics (NPs) have increasingly been found in the environment. Until recently, most MPs/NPs toxicological research has been done in aquatic systems resulting in a gap in knowledge regarding terrestrial systems. Plastics have been shown to enter the circulatory system of humans, and can accumulate within organs, little is known about the effect this has on health. Heart disease is the leading cause of death globally, so it's critical to understand the possible impacts MPs/NPs have on the heart. The Drosophila model has been growing in popularity within the toxicology field, it allows for affordable and rapid research on the impacts of a variety of toxins, including plastics. Some research has examined toxicological effects of plastics on the fly, evaluating the effects on mortality, fecundity, development, and locomotion. However, no one has studied the effects on the Drosophila heart. We utilize the Drosophila model to identify the potential effects of oral exposure to polystyrene MPs (1 µm in diameter) and NPs (0.05 µm in diameter) particles on heart function. Flies were exposed to 1.4 × 1011 particles/d/kg of larvae for MPs and 1.2 × 1018 particles/d/kg of larvae for NPs from egg to pupal eclosion. Heart function was then analyzed utilizing semi-intact dissections and Semi-automatic Optic Heartbeat Analysis software (SOHA). Following exposure to MPs and NPs we see sexually dimorphic changes to heart size and function. This study highlights the importance of additional Drosophila MPs/NPs research to identify the molecular mechanisms behind these changes.

Refractory amiodarone-induced thyrotoxicosis requiring adjunctive cholestyramine treatment.

Amiodarone is an antiarrhythmic drug which may be associated with thyroid dysfunction. Type I amiodarone-induced thyrotoxicosis (AIT) is treated with thionamides and type II AIT is treated with glucocorticoids. Combined therapy is used in mixed or indeterminate forms. When medical treatment is unsuccessful, radioiodine ablation or thyroidectomy is considered. This report reviews a case of AIT refractory to conventional treatment. Despite high doses of methimazole and prednisone, the patient remained clinically and biochemically thyrotoxic. Cholestyramine, a bile salt sequestrant, was used as an off-label adjunctive treatment resulting in significant improvement and achievement of euthyroidism that may also be in part due to the expected natural timeline of recovery from AIT after several months. The patient subsequently trended towards hypothyroidism with symptomatic weight gain and cold intolerance for which he was initiated on levothyroxine.

Evidence of spontaneous cardiac-locomotor coupling during daily activities in healthy adults.

Introduction: One way to improve exercise performance and protect heart health is the extended synchronization of the stepping with the diastolic phase of the cardiac cycle. Cardiac-locomotor coupling (CLC) happens when the step rate (SR) equals the heart rate (HR). The extent of CLC in daily life is unknown. This study aims to analyze spontaneous occurrences of CLC during daily activities. Methods: A retrospective analysis of daily life recordings from a wrist-worn sensor was undertaken (PMData, N = 16, 5 months duration). The deviation between HR and SR was used to define CLC (deviation ≤ 1%) and weak CLC (1%< deviation ≤ 10%). The occurrence and the probability of CLC during everyday life were computed from the recordings. The CLC occurrences were stratified depending on the duration and intensity of the physical activity. Finally, a Monte Carlo simulation was run to evaluate the probability of random occurrences of CLC vs. the observed recordings. Results: Participants couple for 5% and weakly couple for 35% of the observational period. The ratio of 1:1 between HR and SR is the dominating occurrence across the study population and this overrepresentation is significant. CLC occurs mostly for long activities. The extent of CLC for various intensities of activity is subject-dependent. The results suggest that CLC is feasible for most people. Conclusions: CLC occurs spontaneously during unsupervised daily activity in everyone in our cohort, which suggests a mechanistic interaction between the cardiac and the locomotor systems. This interaction should be investigated for medical rehabilitation and sports applications in the future.

Essential Roles of PIEZO1 in Mammalian Cardiovascular System: From Development to Diseases.

Mechanical force is the basis of cardiovascular development, homeostasis, and diseases. The perception and response of mechanical force by the cardiovascular system are crucial. However, the molecular mechanisms mediating mechanotransduction in the cardiovascular system are not yet understood. PIEZO1, a novel transmembrane mechanosensitive cation channel known for its regulation of touch sensation, has been found to be widely expressed in the mammalian cardiovascular system. In this review, we elucidate the role and mechanism of PIEZO1 as a mechanical sensor in cardiovascular development, homeostasis, and disease processes, including embryo survival, angiogenesis, cardiac development repair, vascular inflammation, lymphangiogenesis, blood pressure regulation, cardiac hypertrophy, cardiac fibrosis, ventricular remodeling, and heart failure. We further summarize chemical molecules targeting PIEZO1 for potential translational applications. Finally, we address the controversies surrounding emergent concepts and challenges in future applications.

Differential effects of physiological agonists on the proteome of platelet-derived extracellular vesicles.

Arterial thrombosis contributes to some of the most frequent causes of mortality globally, such as myocardial infarction and stroke. Platelets are essential mediators of physiological haemostasis and pathological thrombosis. Platelet activation is controlled by a multitude of signalling pathways. Upon activation, platelets shed platelet-derived extracellular vesicles (pEVs). In this Special Issue: Extracellular Vesicles, Moon et al. investigate the impact of various platelet agonists (thrombin, ADP, collagen) on the proteome of pEVs. The study demonstrates that pEVs exhibit an agonist-dependent altered proteome compared to their parent cells, with significant variations in proteins related to coagulation, complement, and platelet activation. The study observes the rapid generation of pEVs following agonist stimulation with specific proteome alterations that underscore an active packaging process. This commentary highlights the implications of their findings and discusses the role of pEV cargo in cardiovascular disease with potential novel therapeutic and diagnostic opportunities.

A novel concern from two sample Mendelian randomization study: The effects of air pollution exposure on the cardiovascular, respiratory, and nervous system.

BACKGROUND: Cardiovascular, respiratory, and nervous system diseases have high morbidity and mortality rates, but the causal relationship between air pollution and these diseases remains controversial. METHODS: We conducted a large-scale genome-wide association (GWAS) study using Mendelian randomization (MR) to investigate the association between air pollution like Nitrogen dioxide (NO2), Nitrogen oxides (NOX), Particulate matter with diameter<2.5µm (PM2.5), Particulate matter with diameter<10µm (PM10) and cardiovascular, respiratory, and nervous system diseases, including acute myocardial infarction, heart failure, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, stroke and Parkinson's disease. This study included 337,199 patients with acute myocardial infarction, 178,726 patients with heart failure, 463,010 patients with asthma, 462,933 patients with COPD, 486,484 patients with pneumonia, 484,598 patients with stroke, and 482,730 patients with Parkinson's disease. All genetic tools were identified from GWAS. The association effects of environmental pollution and these diseases were investigated using MR analysis, sensitivity analysis with heterogeneity, pleiotropy test, and leave-one-out test. RESULTS: Our MR analysis showed the association between NOX and the development of COPD and stroke (Odds ratio (OR)=1.010, 95 % Confidence interval (CI): 1.000～1.020, P=0.046; OR=1.017, 95 %CI:1.003-1.031, P=0.019), the association between PM2.5 and the development of asthma, COPD and stroke (OR=1.013, 95 %CI:1.003-1.024, P=0.011; OR=1.010, 95 %CI:1.000-1.019, P=0.035; OR=1.019, 95 %CI:1.004-1.033, P=0.012). No significant associations were found between the rest of the air pollution exposures and diseases. Leave-one-out sensitivity analysis showed stable results. CONCLUSIONS: The study clarifies the relationship between air pollution and cardiovascular, respiratory, and nervous system diseases, providing valuable evidence for environmental pollution prevention and population health monitoring, and provides a clear direction and evidence for the subsequent investigation of the association between air pollution and diseases.

Diagnostic accuracy of alternative biomarkers for acute aortic syndrome: a systematic review.

BACKGROUND: D-dimer is the only biomarker currently recommended in guidelines for the diagnosis of acute aortic syndrome (AAS). We undertook a systematic review to determine whether any alternative biomarkers could be useful in AAS diagnosis. METHODS: We searched electronic databases (including MEDLINE, EMBASE and the Cochrane Library) from inception to February 2024. Diagnostic studies were eligible if they examined biomarkers other than D-dimer for diagnosing AAS compared with a reference standard test in people presenting to the ED with symptoms of AAS. Case-control studies were identified but excluded due to high risk of bias. Selection of studies, data extraction and risk of bias assessments using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool were undertaken independently by at least two reviewers. We used narrative synthesis to summarise the findings. RESULTS: We identified 2017 citations, included 13 cohort studies (n=76-999), and excluded 38 case-control studies. Methodological quality was variable, with most included studies having unclear or high risk of bias and applicability concerns in at least one item of the QUADAS-2 tool. Only two studies reported biomarkers with sensitivity and specificity comparable to D-dimer (ie, >90% and >50%, respectively). Wang et al reported 99.1% sensitivity and 84.9% specificity for soluble ST2; however, these findings conflicted with estimates of 58% sensitivity and 70.8% specificity reported in another study. Chun and Siu reported 95.6% sensitivity and 56.1% specificity for neutrophil count, but this has not been confirmed elsewhere. CONCLUSION: There are many potential alternative biomarkers for AAS but few have been evaluated in more than one study, study designs are often weak and reported biomarker accuracy is modest or inconsistent between studies. Alternative biomarkers to D-dimer are not ready for routine clinical use. PROSPERO REGISTRATION NUMBER: CRD42022252121.

Effects of weightlessness on the cardiovascular system: a systematic review and meta-analysis.

Background: The microgravity environment has a direct impact on the cardiovascular system due to the fluid shift and weightlessness that results in cardiac dysfunction, vascular remodeling, and altered Cardiovascular autonomic modulation (CAM), deconditioning and poor performance on space activities, ultimately endangering the health of astronauts. Objective: This study aimed to identify the acute and chronic effects of microgravity and Earth analogues on cardiovascular anatomy and function and CAM. Methods: CINAHL, Cochrane Library, Scopus, Science Direct, PubMed, and Web of Science databases were searched. Outcomes were grouped into cardiovascular anatomic, functional, and autonomic alterations, and vascular remodeling. Studies were categorized as Spaceflight (SF), Chronic Simulation (CS), or Acute Simulation (AS) based on the weightlessness conditions. Meta-analysis was performed for the most frequent outcomes. Weightlessness and control groups were compared. Results: 62 articles were included with a total of 963 participants involved. The meta-analysis showed that heart rate increased in SF [Mean difference (MD) = 3.44; p = 0.01] and in CS (MD = 4.98; p < 0.0001), whereas cardiac output and stroke volume decreased in CS (MD = -0.49; p = 0.03; and MD = -12.95; p < 0.0001, respectively), and systolic arterial pressure decreased in AS (MD = -5.20; p = 0.03). According to the qualitative synthesis, jugular vein cross-sectional area (CSA) and volume were greater in all conditions, and SF had increased carotid artery CSA. Heart rate variability and baroreflex sensitivity, in general, decreased in SF and CS, whereas both increased in AS. Conclusion: This review indicates that weightlessness impairs the health of astronauts during and after spaceflight, similarly to the effects of aging and immobility, potentially increasing the risk of cardiovascular diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020215515.

Mechanisms of Abnormal Lipid Metabolism in the Pathogenesis of Disease.

Lipid metabolism is a critical component in preserving homeostasis and health, and lipids are significant chemicals involved in energy metabolism in living things. With the growing interest in lipid metabolism in recent years, an increasing number of studies have demonstrated the close relationship between abnormalities in lipid metabolism and the development of numerous human diseases, including cancer, cardiovascular, neurological, and endocrine system diseases. Thus, understanding how aberrant lipid metabolism contributes to the development of related diseases and how it works offers a theoretical foundation for treating and preventing related human diseases as well as new avenues for the targeted treatment of related diseases. Therefore, we discuss the processes of aberrant lipid metabolism in various human diseases in this review, including diseases of the cardiovascular system, neurodegenerative diseases, endocrine system diseases (such as obesity and type 2 diabetes mellitus), and other diseases including cancer.

Long-term systemic effects of metabolic bariatric surgery: A multidisciplinary perspective.

Background: Obesity is a global health crisis with profound implications on various body systems, contributing to a series of comorbidities. Metabolic Bariatric Surgery (MBS) has emerged as an effective treatment option for severe obesity, with significant weight reduction and potential systemic physiological alterations. Objectives: This narrative review aims to provide a comprehensive analysis of the long-term effects of MBS on a wide array of body systems, including the heart, liver, kidneys, reproductive system, skin, lungs, digestive tract, pancreas, and blood, as well as related cancers of these organs. Methods: A systematic search was conducted in academic databases (PubMed, ISI Web of Science, and Scopus) for observational studies and reviews published between July 2000 and December 2023, investigating the association between MBS and the subsequent function of different organ systems. High-quality studies were prioritized to ensure reliable evidence synthesis. Results: MBS has demonstrated favorable outcomes in reducing cardiovascular disease risk, improving cardiac function, and alleviating heart failure symptoms. It has also been associated with improved respiratory function, remission of obstructive sleep apnea, and reduced cancer incidence and mortality. Additionally, MBS has shown benefits in managing gastrointestinal disorders, enhancing glycemic control, and promoting pancreatic beta-cell regeneration in type 2 diabetes mellitus. However, some methods of MBS are associated with a higher risk of cholelithiasis, GERD, and pancreatic exocrine insufficiency. Conclusion: MBS has far-reaching systemic effects beyond weight loss, offering potential long-term benefits for various organ systems and comorbidities associated with obesity. For many patients with severe obesity, the potential benefits of Metabolic and Bariatric Surgery (MBS) can outweigh the associated risks. However, careful evaluation by a qualified healthcare professional is crucial to determine candidacy and ensure a successful outcome. Further research is needed to fully elucidate the long-term impacts and tailor personalized treatment approaches.

Challenging chest pain: salmonella myopericarditis.

Salmonella infections have been associated with cardiovascular complications, including myocarditis and myopericarditis. This presentation of Salmonella myopericarditis highlights key clinical features to aid in diagnosis and the importance of prompt treatment with antibiotics, colchicine and non-steroidal anti-inflammatory drugs (NSAIDs).

Multifractal analysis of heart rate variability in pregnancy during sleep.

Understanding the complex dynamics of heart rate variability (HRV) during pregnancy is crucial for monitoring both maternal well-being and fetal health. In this study, we use the Multifractal Detrended Fluctuations Analysis approach to investigate HRV patterns in pregnant individuals during sleep based on RR interval maxima (MM fluctuations). In addition, we study the type of multifractality within MM fluctuations, that is, if it arises from a broad probability density function or from varying long-range correlations. Furthermore, to provide a comprehensive view of HRV changes during sleep in pregnancy, classical temporal and spectral HRV indices were calculated at quarterly intervals during sleep. Our study population consists of 21 recordings from nonpregnant women, 18 from the first trimester (early-pregnancy) and 18 from the second trimester (middle-pregnancy) of pregnancy. Results. There are statistically significant differences ( p -value < 0.05) in mean heart rate, rms heart rate, mean MM fluctuations, and standard deviation of MM fluctuations, particularly in the third and fourth quarter of sleep between pregnant and non-pregnant states. In addition, the early-pregnancy group shows significant differences ( p -value < 0.05) in spectral indices during the first and fourth quarter of sleep compared to the non-pregnancy group. Furthermore, the results of our research show striking similarities in the average multifractal structure of MM fluctuations between pregnant and non-pregnant states during normal sleep. These results highlight the influence of different long-range correlations within the MM fluctuations, which could be primarily associated with the emergence of sleep cycles on multifractality during sleep. Finally, we performed a separability analysis between groups using temporal and spectral HRV indices as features per sleep quarter. Employing only three features after Principal Component Analysis (PCA) to the original feature set, achieving complete separability among all groups appears feasible. Using multifractal analysis, our study provides a comprehensive understanding of the complex HRV patterns during pregnancy, which holds promise for maternal and fetal health monitoring. The separability analysis also provides valuable insights into the potential for group differentiation using simple measures such as mean heart rate, rms heart rate, and mean MM fluctuations or in the transformed feature space based on PCA.

A Systematic Review and Meta-Analysis of Randomized Trials to Evaluate the Impact of Exercise on Heart Rate Variability Post-Bariatric Surgery.

Bariatric surgery is an approach used to treat patients with obesity in a small minority of eligible patients. Non-pharmacological therapies are important to maintain decent health status post-bariatric surgery. We performed a systematic review with meta-analysis to evaluate the effects of exercise on heart rate variability (HRV) in patients submitted to bariatric surgery. The searches were made via MEDLINE/PubMed (via the National Library of Medicine), EMBASE, Web of Science, and Scopus databases. We included non-blind, single-, or double-blind randomized control trials in patients older than 18 years of age submitted to bariatric surgery. The intervention group should be submitted to an exercise training protocol, including aerobic, strength, and other exercise modality after bariatric surgery. We documented 245 studies, and after screening and eligibility phases, only 4 were included. We observed no significant change for the SDNN: subtotal = 19.74 (CI: -4.98, 44.45), p = 0.12, I2 = 85% (very low quality of evidence); pNN50: subtotal = 13.09 (CI: -9.17, 35.35), p = 0.25, I2 = 93% (very low quality of evidence); RMSSD: subtotal = 8.44 (CI: -3.61, 25.50), p = 0.17, I2 = 95% (very low quality of evidence); SD1: subtotal = 9.36 (CI: -4.48, 23.21), p = 0.19, I2 = 96% (very low quality of evidence). We could not detect significant effects of exercise on resting HRV after bariatric surgery. The low certainty of the results via the evidence level analysis suggest further studies might be beneficial.

Alterations in plasma proteome during acute COVID-19 and recovery.

BACKGROUND: The severe course of COVID-19 causes cardiovascular injuries, although the mechanisms involved are still not fully recognized, linked, and understood. Their characterization is of great importance with the establishment of the conception of post-acute sequelae of COVID-19, referred to as long COVID, where blood clotting and endothelial abnormalities are believed to be the key pathomechanisms driving circulatory system impairment. METHODS: The presented study investigates temporal changes in plasma proteins in COVID-19 patients during hospitalization due to SARS-CoV-2 infection and six months after recovery by targeted SureQuant acquisition using PQ500 panel. RESULTS: In total, we identified 167 proteins that were differentially regulated between follow-up and hospitalization, which functionally aggregated into immune system activation, complement and coagulation cascades, interleukins signalling, platelet activation, and extracellular matrix organization. Furthermore, we found that temporal quantitative changes in acute phase proteins correlate with selected clinical characteristics of COVID-19 patients. CONCLUSIONS: In-depth targeted proteome investigation evidenced substantial changes in plasma protein composition of patients during and recovering from COVID-19, evidencing a wide range of functional pathways induced by SARS-CoV-2 infection. In addition, we show that a subset of acute phase proteins, clotting cascade regulators and lipoproteins could have clinical value as potential predictors of long-term cardiovascular events in COVID-19 convalescents.

Simulated Microgravity Alters Gene Regulation Linked to Immunity and Cardiovascular Disease.

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long-Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space.

The Effects of Caffeine on Blood Platelets and the Cardiovascular System through Adenosine Receptors.

Caffeine is the most popular and widely consumed behaviourally active substance in the world. This review describes the influence of caffeine on the cardiovascular system, with a special focus on blood platelets. For many years, caffeine was thought to have a negative effect on the cardiovascular system mainly due to increasing blood pressure. However, more recent data suggest that habitual caffeine consumption may reduce the risk of cardiovascular disease and hypertension. This could be a significant finding as cardiovascular disease is the leading cause of death worldwide. Caffeine is known to inhibit A1 adenosine receptors, through which it is believed to modulate inter alia coronary blood flow, total peripheral resistance, diuresis, and heart rate. It has been shown that coffee possesses antiplatelet activity, but depending on the dose and the term of its use, caffeine may stimulate or inhibit platelet reactivity. Also, chronic exposure to caffeine may sensitize or upregulate the adenosine receptors in platelets causing increased cAMP accumulation and anti-aggregatory effects and decrease calcium levels elicited by AR agonists. The search for new, selective, and safe AR agonists is one of the new strategies for improving antiplatelet therapy involving targeting multiple pathways of platelet activation. Therefore, this review examines the AR-dependent impact of caffeine on blood platelets in the presence of adenosine receptor agonists.