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Pubblicazioni recenti - cardiac failure
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Interlaboratory variation for NT-proBNP among Swedish laboratories in an external quality program 2011-2021.
Clin Chem Lab Med2023 Mar;():. doi: 10.1515/cclm-2023-0051.
Lundgren Morgan, Ridefelt Peter, Karlsson Mathias, Norling Anna, Larsson Anders,
Abstract
OBJECTIVES:
NT-proBNP is frequently used for ruling out heart failure. Different cut-offs are used depending on the clinical context, e.g. an acute or chronic condition. Medical decision limits have been suggested at 125 and 300 ng/L or 400 ng/L in international guidelines. However, there is limited standardization between NT-proBNP methods and using the same blood sample might cause different treatment of patients.
METHODS:
Data from the external quality assessment program for NT-proBNP from Equalis, Sweden, were extracted for the period 2011-2021, and categorized according to manufacturer. Manufacturer median NT-proBNP values were compared to total median values. CV% was calculated for each manufacturer and in comparison to different levels of NT-proBNP.
RESULTS:
Roche was the most common method, and its median results were closest to the median consensus results. When looking at the total CV at NT-proBNP levels in the range of 0-500 ng/L, the total CV varied from 4 to 27%. During 2019-2021, Siemens (Immulite, Centaur, Atellica) yielded results 16-20% above the consensus median depending on sample level. Similarly, Abbott was 5-7% above, while Roche and Siemens Stratus were 1% respectively 6-10% below the consensus median.
CONCLUSIONS:
The introduction of new manufacturers and methods in 2017 have caused the agreement between manufacturers to decline. This highlights the need for a common calibrator and reference materials, particularly since medical decision limits in guidelines, e.g. European Society of Cardiology 2021, which are mostly based on Roche methods, do not take these method differences into account.
© 2023 the author(s), published by De Gruyter, Berlin/Boston.
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Serial assessment of biomarkers and heart failure outcomes in patients with atrial fibrillation.
Eur J Heart Fail2023 Mar;():. doi: 10.1002/ejhf.2844.
Oyama Kazuma, Giugliano Robert P, Ruff Christian T, Berg David D, Jarolim Petr, Tang Minao, Park Jeong-Gun, Lanz Hans J, Antman Elliott M, Braunwald Eugene, Morrow David A,
Abstract
AIMS:
Cardiac functional and structural remodeling in patients with atrial fibrillation (AF) contributes to development of heart failure (HF) as their major cardiovascular comorbidity. Circulating biomarkers may reflect these cardiac alterations.
METHODS AND RESULTS:
ENGAGE AF-TIMI 48 was a randomized trial of edoxaban vs warfarin in 21,105 patients with AF. We performed a nested biomarker study in 8,765 patients, analyzing high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) at baseline and 12 months. Of 8765 patients, 5207 had a history of HF, among whom 3996 had known ejection fraction (EF): 926 with reduced EF (HFrEF; ?40%), 1043 with mildly-reduced EF (HFmrEF; 40-49%), and 2027 with preserved EF (HFpEF; ?50%). Elevated baseline hsTnT, NT-proBNP, and GDF-15 were associated with higher risk of hospitalization for HF (HHF)/HF death overall and in subpopulations defined by HF history and EF (P0.05 for each). Patients who had an increase in or had persistently elevated values in any of the three biomarkers over 12 months were at higher risk for HHF/HF death in overall population (P
CONCLUSION:
Serial measurement of hsTnT, NT-proBNP, and GDF-15 revealed that higher baseline values, and increasing or persistently elevated values over 1 year are associated with higher risk of HF outcomes in patients with AF regardless of HF history or HF phenotype based on EF.
This article is protected by copyright. All rights reserved.
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Current and future trial design in refractory cardiogenic shock.
Eur J Heart Fail2023 Mar;():. doi: 10.1002/ejhf.2838.
Arrigo Mattia, Blet Alice, Morley-Smith Andrew, Aissaoui Balanant Nadia, Baran David A, Bayes-Genis Antoni, Chioncel Ovidiu, Desch Steffen, Karakas Mahir, Moller Jacob Eifer, Poess Janine, Price Susanna, Zeymer Uwe, Mebazaa Alexandre,
Abstract
Cardiogenic shock is a life-threatening syndrome of peripheral hypoperfusion and organ dysfunction due to primary cardiac disease. Few adequately designed randomized clinical trials provide guidance on the optimal management strategies, which frequently includes vasoactive drugs, circulatory and ventilatory support, and reversal of any underlying cause, including coronary revascularization in case of acute myocardial infarction. Management is largely based on experience rather than evidence-based recommendations and patient outcomes remain poor. Particular attention is currently given to refractory patients (i.e., not responding to medical treatment) with a growing number of studies investigating various modalities of mechanical circulatory support. This consensus document summarizes the output from the third Critical Care Clinical Trialists Workshop, where a group of experts convened to discuss, debate, and reflect on approaches related to trials in refractory cardiogenic shock, to provide recommendations for the design of future trials. Invited participants included clinical trialists, clinicians (including cardiologists, intensive care specialists, anaesthesiologists, and cardiac surgeons), epidemiologists, patient representatives, regulators from the United States and Europe, United States federal grant managers, and industry representatives. Special attention is given to current and future definitions of cardiogenic shock including refractory states, recent and ongoing clinical trials in refractory cardiogenic shock and future directions in light of the most recent literature.
This article is protected by copyright. All rights reserved.
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Fraction of Osteocalcin Endothelial Progenitor Cells and Cardiovascular Risk.
Circ Res2023 Mar;():. doi: 10.1161/CIRCRESAHA.122.322407.
Ozcan Ilke, Kanaji Yoshihisa, Rajotia Arush, Toya Takumi, Akhiyat Nadia, Morse David, Lerman Lilach O, Lerman Amir,
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Reply to: Xie et al. What is the optimal dose of neurohormonal modulators in patients with heart failure? The higher the better?
Eur J Heart Fail -
Patient after treatment of Hodgkin's lymphoma: A typical? cardiological patient. Author's reply.
Kardiol Pol2023 ;81(3):316-317. doi: 10.33963/KP.a2023.0076.
St?pie? Konrad, Del Carmen Yika Alicia, Bilecki Krzysztof, Furczy?ski Jakub, Nowak Karol, St?pie? Adam, Nessler Jadwiga, Zalewski Jaros?aw, Konduracka Ewa,
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Is robotic assistance an added value in minimally invasive mitral valve surgery? A meta-analysis from propensity score-matched series.
Asian Cardiovasc Thorac Ann2023 Mar;():2184923231166352. doi: 10.1177/02184923231166352.
Jegaden Olivier, Al Shamry Adel, Ashafy Salah, Mahdi Alhaitham, Eker Armand,
Abstract
OBJECTIVES:
There is still ongoing debate about the benefits of robotic assistance (R-MVS) in comparison with video assistance (V-MVS) in minimally invasive mitral valve surgery. This study aims to update the current evidence.
METHODS:
Three propensity score-matched studies published from 2011 to 2021 were included with a total of 1193 patients operated on from 2005 (R-MVS: 536, V-MVS: 657). Data regarding early mortality, postoperative event, and time-related outcomes were extracted and submitted to a meta-analysis using weighted random-effects modeling.
RESULTS:
The incidence of early mortality, stroke, renal failure, conversion, atrial fibrillation, and prolonged ventilation were similar, all in the absence of heterogeneity. Reoperation for bleeding (odds ratio [OR]: 0.36, 95% confidence interval [CI] 0.16-0.81, ?=?0.01) and the need for blood transfusion (OR: 0.30, 95% CI, 0.20-0.56, ?=?0.001) were significantly lower in V-MVS group. Regarding time-related outcomes, there was evidence for important heterogeneity of treatment effect among the studies. Operative times were longer in R-MVS: differences in means were 20.7?min for cross-clamp time (95% CI, 9.07-32.3, ?=?0.001), 20.7?min for cardiopulmonary bypass time (95% CI, 2.5-38.9, ?=?0.03) and 40.2?min for total operative time (95% CI, 24.5-55.8, ?0.001). Intensive care unit stay and hospital stay were reported in one study, and longer after R-MVS compared to V-MVS; the differences in means were 0.17 days (?=?0.005) and 0.6 days (?=?0.017), respectively. Total cost of both procedures was reported in an additional dedicated propensity score-matched series including 448 patients; it was 21% higher for R-MVS than for V-MVS.
CONCLUSIONS:
This meta-analysis showed excellent outcomes of both video and robotic techniques with low incidence of morbidity and mortality. However, there is no evidence for an added value of robotic assistance in comparison with video assistance; the drawbacks of mini access are reported higher regardless the induced over cost.
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Association between lactate/albumin ratio and mortality in patients with heart failure after myocardial infarction.
ESC Heart Fail2023 Mar;():. doi: 10.1002/ehf2.14359.
Chen Yang, Yang Ke, Wu Bingyuan, Lin Wanwen, Chen Simin, Xu Xiaochun, Peng Chaoquan, Xie Dongmei,
Abstract
AIMS:
Lactate/albumin ratio (L/A) is a recognized prognostic index of patients with heart failure (HF) after myocardial infarction (MI). We aim to evaluate the prognostic value of L/A ratio in predicting in-hospital mortality for those patients.
METHODS AND RESULTS:
We enrolled qualified patients from Medical Information Mart for Intensive Care IV database for retrospective study. A receiver operating characteristic (ROC) curve of the subjects was applied to determine the predicted value and the best cut-off value of L/A on admission. Univariate/multivariate Cox regression analysis and restricted cubic splines (RCS) were performed to identify the association between hospital admission and hospital mortality. The Kaplan-Meier (KM) method was used to draw the survival curve of the two groups with different L/A levels at admission. L/A values at admission were significantly higher in the death groups than the survival groups [1.36 (1.20) vs. 0.62 (0.36), P
CONCLUSIONS:
Elevated L/A ratio on admission is an independent predictor of high in-hospital mortality in post-MI heart failure patients, which proved to be better than lactate, Sequential Organ Failure Assessment score and other related indicators.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Inflammatory biomarkers in assessing severity and prognosis of immune checkpoint inhibitor-associated cardiotoxicity.
ESC Heart Fail2023 Mar;():. doi: 10.1002/ehf2.14340.
Liang Lin, Cui Chanjuan, Lv Dan, Li Yiqun, Huang Liyan, Feng Jiayu, An Tao, Tian Pengchao, Yang Ke, Hu Linjun, Gao Lizhen, Zhang Jian, Zhang Yuhui, Ma Fei, Wang Yanfeng,
Abstract
AIMS:
Inflammatory biomarkers, including CRP, the neutrophil-to-lymphocyte ratio (NLR), and the neutrophil-to-eosinophil ratio (NER), may predict outcomes in cancer. However, their value in immune checkpoint inhibitor (ICI) therapy-associated cardiotoxicity remains elusive. We aimed to characterize the relationship of inflammatory markers with severity of ICI-related cardiotoxicities (iRCs) and prognosis among patients with iRCs.
METHODS:
Patients who were diagnosed with iRCs between January 2019 and December 2021 were retrospectively enrolled and were dichotomized based on iRC severity into low-grade (grade 1-2) vs. high-grade (grade 3-4) groups.
RESULTS:
Forty-seven patients were included. The median time-to-event from first ICI infusion to onset of iRCs was 35 days (IQR: 19.0-65.5 days). When compared with respective baseline values, cardiac biomarkers and inflammatory markers were significantly elevated at onset of iRCs. Compared with low-grade iRCs, NER at iRC onset was significantly increased among patients with high-grade iRCs (Group × Time, P
CONCLUSIONS:
In patients who develop iRCs, NER is significantly elevated at iRC onset, and higher NER correlates with greater iRC severity and higher mortality. Larger datasets are needed to validate these findings.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Clinical course of patients with hypertrophic cardiomyopathy away from tertiary referral care.
ESC Heart Fail2023 Mar;():. doi: 10.1002/ehf2.14345.
Garmany Ramin, Bos J Martijn, Ommen Steve R, Ackerman Michael J, Geske Jeffrey B,
Abstract
AIMS:
Data on the clinical course of hypertrophic cardiomyopathy (HCM) are mainly derived from tertiary HCM centre studies, and knowledge of clinical outcomes of patients leaving specialty care and returning to local physicians is limited due to gaps between clinical encounters or complete loss of follow-up. This survey aims to describe the clinical course of HCM in patients following their evaluation at a tertiary referral centre.
METHODS AND RESULTS:
A comprehensive outcomes survey was developed and sent to 4495 eligible patients with HCM previously evaluated at Mayo Clinic. Questions assessed general well-being, New York Heart Association class, procedures performed, and probable HCM-triggered ventricular arrhythmic events (VAEs) since last visit. In total, 2058 patients (mean age 63 ± 15 years; 42% female) responded to the survey covering a total of 10 510 patient-years with an average of 5.4 ± 6.4 years of follow-up since their last on-campus/virtual visit to Mayo Clinic. During their time away from specialty care, 20% of patients reported having cardiac-related hospitalizations and 25% reported having cardiac-related procedures. Similar to high-risk referral cohorts, 5% of patients reported VAEs with an event rate of 0.98 events/100 patient-years. The prevalence of atrial fibrillation, syncope, pre-syncope, cardiac-related hospitalizations, and VAEs during time away from specialty care increased significantly with increasing New York Heart Association class (P
CONCLUSIONS:
Acknowledging ascertainment bias, the clinical course of patients away from tertiary care may be more severe than previously anticipated. Among those with exertional symptoms, HCM-related morbidity increased substantially. Higher risk HCM patients should remain in contact with HCM specialty care.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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The Singapore Experience With Uncontrolled Gout: Unmet Needs in the Management of Patients.
Cureus2023 Mar;15(3):e36682. doi: 10.7759/cureus.36682.
Lee Zheng Cong, Santosa Anindita, Khor Andrew Yu Keat, Sriranganathan Melonie K,
Abstract
Gout is the most common type of inflammatory arthritis, and its impact on cardiovascular health and quality of life is often underestimated. The prevalence and incidence of gout are increasing globally. Further, ischemic heart disease (IHD) and chronic kidney disease (CKD) are prevalent in gout patients. Some unmet needs for gout management include physicians' low initiation rate of urate-lowering therapy (ULT) and poor treatment adherence in patients with gout. There is also a lack of randomized controlled trials that establish safe doses of acute and long-term treatment for gout, particularly in patients with IHD and stage 4 CKD and above (including end-stage renal failure). Furthermore, there is also a lack of studies showing optimal serum uric acid (SUA) target and validated clinical outcome measures, including disease activity and remission criteria for gout tailored to treat-to-target approaches and the high cost of newer gout medications. The causal relationship between asymptomatic hyperuricemia or gout with comorbidities such as IHD and CKD has yet to be fully elucidated. There is a pressing need for collaborative international efforts to address the overall suboptimal management of gout.
Copyright © 2023, Lee et al.
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Understanding the Mechanisms and Treatment of Heart Failure: Quantitative Systems Pharmacology Models with a Focus on SGLT2 Inhibitors and Sex-Specific Differences.
Pharmaceutics2023 Mar;15(3):. doi: 1002.
Ndiaye Jean François, Nekka Fahima, Craig Morgan,
Abstract
Heart failure (HF), which is a major clinical and public health challenge, commonly develops when the myocardial muscle is unable to pump an adequate amount of blood at typical cardiac pressures to fulfill the body's metabolic needs, and compensatory mechanisms are compromised or fail to adjust. Treatments consist of targeting the maladaptive response of the neurohormonal system, thereby decreasing symptoms by relieving congestion. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which are a recent antihyperglycemic drug, have been found to significantly improve HF complications and mortality. They act through many pleiotropic effects, and show better improvements compared to others existing pharmacological therapies. Mathematical modeling is a tool used to describe the pathophysiological processes of the disease, quantify clinically relevant outcomes in response to therapies, and provide a predictive framework to improve therapeutic scheduling and strategies. In this review, we describe the pathophysiology of HF, its treatment, and how an integrated mathematical model of the cardiorenal system was built to capture body fluid and solute homeostasis. We also provide insights into sex-specific differences between males and females, thereby encouraging the development of more effective sex-based therapies in the case of heart failure.
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Cyclocreatine Phosphate: A Novel Bioenergetic/Anti-Inflammatory Drug That Resuscitates Poorly Functioning Hearts and Protects against Development of Heart Failure.
Pharmaceuticals (Basel)2023 Mar;16(3):. doi: 453.
Elgebaly Salwa A, Van Buren Charles, Todd Robert, Poston Robert, Arafa Reem K, El-Khazragy Nashwa, Kreutzer Donald, Rabie Mostafa A, Mohamed Ahmed F, Ahmed Lamiaa A, El Sayed Nesrine S,
Abstract
Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-?, TGF-?, and caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.
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Chronic Propafenone Application Increases Functional K2.1 Expression In Vitro.
Pharmaceuticals (Basel)2023 Mar;16(3):. doi: 404.
Li Encan, Kool Willy, Woolschot Liset, van der Heyden Marcel A G,
Abstract
Expression and activity of inwardly rectifying potassium (K) channels within the heart are strictly regulated. K channels have an important role in shaping cardiac action potentials, having a limited conductance at depolarized potentials but contributing to the final stage of repolarization and resting membrane stability. Impaired K2.1 function causes Andersen-Tawil Syndrome (ATS) and is associated with heart failure. Restoring K2.1 function by agonists of K2.1 (AgoKirs) would be beneficial. The class 1c antiarrhythmic drug propafenone is identified as an AgoKir; however, its long-term effects on K2.1 protein expression, subcellular localization, and function are unknown. Propafenone's long-term effect on K2.1 expression and its underlying mechanisms in vitro were investigated. K2.1-carried currents were measured by single-cell patch-clamp electrophysiology. K2.1 protein expression levels were determined by Western blot analysis, whereas conventional immunofluorescence and advanced live-imaging microscopy were used to assess the subcellular localization of K2.1 proteins. Acute propafenone treatment at low concentrations supports the ability of propafenone to function as an AgoKir without disturbing K2.1 protein handling. Chronic propafenone treatment (at 25-100 times higher concentrations than in the acute treatment) increases K2.1 protein expression and K2.1 current densities in vitro, which are potentially associated with pre-lysosomal trafficking inhibition.
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Cardiometabolic Care: Assessing Patients with Diabetes Mellitus with No Overt Cardiovascular Disease in the Light of Heart Failure Development Risk.
Nutrients2023 Mar;15(6):. doi: 1384.
Chrysohoou Christina, Fragoulis Christos, Leontsinis Ioannis, Gastouniotis Ioannis, Fragouli Dimitra, Georgopoulos Maximos, Mantzouranis Emmanouil, Noutsou Marina, Tsioufis Konstantinos P,
Abstract
The mechanisms leading to the development of heart failure (HF) in diabetes mellitus (DM) patients are multifactorial. Assessing the risk of HF development in patients with DM is valuable not only for the identification of a high-risk subgroup, but also equally important for defining low-risk subpopulations. Nowadays, DM and HF have been recognized as sharing similar metabolic pathways. Moreover, the clinical manifestation of HF can be independent of LVEF classification. Consequently, approaching HF should be through structural, hemodynamic and functional evaluation. Thus, both imaging parameters and biomarkers are important tools for the recognition of diabetic patients at risk of HF manifestation and HF phenotypes, and arrhythmogenic risk, and eventually for prognosis, aiming to improve patients' outcomes utilizing drugs and non-pharmaceutical cardioprotective tools such as diet modification.
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Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients.
Microorganisms2023 Mar;11(3):. doi: 755.
Masetti Marco, Scuppa Maria Francesca, Aloisio Alessio, Giovannini Laura, Borgese Laura, Manno Stefania, Tazza Beatrice, Pascale Renato, Bonazzetti Cecilia, Caroccia Natascia, Sabatino Mario, Spitaleri Giosafat, Viale Pierluigi, Giannella Maddalena, Potena Luciano,
Abstract
Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21-11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT
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Angiotensin-Converting Enzyme 2 Expression and Severity of SARS-CoV-2 Infection.
Microorganisms2023 Feb;11(3):. doi: 612.
Alabsi Sarah, Dhole Atharva, Hozayen Sameh, Chapman Scott A,
Abstract
Angiotensin-converting enzyme 2 (ACE2), first discovered in 2000, serves as an important counterregulatory enzyme to the angiotensin II-mediated vasoconstrictive, pro-inflammatory, and pro-fibrotic actions of the renin-angiotensin system (RAS). Conversion of angiotensin II to the peptide angiotensin 1-7 (ANG 1-7) exerts protective vasodilatory, anti-inflammatory, and anti-fibrotic actions through interaction with the MasR receptor. There are many important considerations when noting the role of ACE2 in the pathogenesis and sequelae of COVID-19 infection. ACE2, in the role of COVID-19 infection, was recognized early in 2020 at the beginning of the pandemic as a cell membrane-bound and soluble binding site for the viral spike protein facilitating entering into tissue cells expressing ACE2, such as the lungs, heart, gut, and kidneys. Mechanisms exist that alter the magnitude of circulating and membrane-bound ACE2 (e.g., SARS-CoV-2 infection, viral variants, patient characteristics, chronic disease states, and the degree of cell surface expression of ACE2) and the influence these mechanisms have on the severity of disease and associated complications (e.g., respiratory failure, systemic inflammatory response syndrome, acute myocarditis, acute kidney injury). Several medications alter the ACE2 receptor expression, but whether these medications can influence the course of the disease and improve outcomes is unclear. In this review, we will discuss what is known about the interrelation of SARS-CoV-2, ACE2 and the factors that may contribute to the variability of its expression and potential contributors to the severity of COVID-19 infection.
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Life-Threatening Cardiogenic Shock Related to Venlafaxine Poisoning-A Case Report with Metabolomic Approach.
Metabolites2023 Feb;13(3):. doi: 353.
Magny Romain, Mégarbane Bruno, Guillaud Pauline, Chevillard Lucie, Auzeil Nicolas, Thiebot Pauline, Voicu Sebastian, Malissin Isabelle, Deye Nicolas, Labat Laurence, Houzé Pascal,
Abstract
Metabolomics in clinical toxicology aim at reliably identifying and semi-quantifying a broad array of endogenous and exogenous metabolites using dedicated analytical methods. Here, we developed a three-step-based workflow to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient who developed life-threatening cardiac failure managed with extracorporeal membrane oxygenation. Both targeted quantitative and untargeted semi-quantitative metabolomic analyses using liquid chromatography hyphenated to high-resolution tandem mass spectrometry were performed to determine the plasma kinetics of venlafaxine, -desmethyl-venlafaxine, and -desmethyl-venlafaxine and to identify sixteen different venlafaxine-derived metabolites including one unknown (, venlafaxine conjugated to a hexosyl-radical), respectively. Correlations between the quantitative metabolomic data and annotated endogenous metabolites suggested impaired amino acid and lipid metabolism, Krebs cycle, and kynurenine pathway. This preliminary study represents a first step towards a more extensive application of toxicometabolomics in clinical toxicology and a useful workflow to identify the biomarkers of toxicity.
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Analysis of PEM Water Electrolyzer Failure Due to Induced Hydrogen Crossover in Catalyst-Coated PFSA Membranes.
Membranes (Basel)2023 Mar;13(3):. doi: 348.
Kuhnert Eveline, Heidinger Mathias, Sandu Daniel, Hacker Viktor, Bodner Merit,
Abstract
Polymer electrolyte membrane water electrolysis (PEMWE) is a leading candidate for the development of a sustainable hydrogen infrastructure. The heart of a PEMWE cell is represented by the membrane electrode assembly (MEA), which consists of a polymer electrolyte membrane (PEM) with catalyst layers (CLs), flow fields, and bipolar plates (BPPs). The weakest component of the system is the PEM, as it is prone to chemical and mechanical degradation. Membrane chemical degradation is associated with the formation of hydrogen peroxide due to the crossover of product gases (H and O). In this paper, membrane failure due to H crossover was addressed in a membrane-focused accelerated stress test (AST). Asymmetric HO and gas supply were applied to a test cell in OCV mode at two temperatures (60 °C and 80 °C). Electrochemical characterization at the beginning and at the end of testing revealed a 1.6-fold higher increase in the high-frequency resistance (HFR) at 80 °C. The hydrogen crossover was measured with a micro-GC, and the fluoride emission rate (FER) was monitored during the ASTs. A direct correlation between the FER and H crossover was identified, and accelerated membrane degradation at higher temperatures was detected.
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Cardiovascular Magnetic Resonance Imaging in Familial Dilated Cardiomyopathy.
Medicina (Kaunas)2023 Feb;59(3):. doi: 439.
Lau Clement, Gul Uzma, Liu Boyang, Captur Gabriella, Hothi Sandeep S,
Abstract
Dilated cardiomyopathy (DCM) is a common cause of non-ischaemic heart failure, conferring high morbidity and mortality, including sudden cardiac death due to systolic dysfunction or arrhythmic sudden death. Within the DCM cohort exists a group of patients with familial disease. In this article we review the pathophysiology and cardiac imaging findings of familial DCM, with specific attention to known disease subtypes. The role of advanced cardiac imaging cardiovascular magnetic resonance is still accumulating, and there remains much to be elucidated. We discuss its potential clinical roles as currently known, with respect to diagnostic utility and risk stratification. Advances in such risk stratification may help target pharmacological and device therapies to those at highest risk.
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