Fragmented QRS, a strong predictor of mortality and major arrhythmic events in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study. Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0. Results: Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p < 0.0001). Conclusion: Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM.

Predictors of pacemaker requirement in patients with implantable loop recorder and unexplained syncope: A systematic review and meta-analysis.

Identifying the underlying cause of unexplained syncope is crucial for appropriate management of recurrent syncopal episodes. Implantable loop recorders (ILRs) have emerged as valuable diagnostic tools for monitoring patients with unexplained syncope. However, the predictors of pacemaker requirement in patients with ILR and unexplained syncope remain unclear. In this study, we shed light on these prognostic factors. PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane CENTRAL were systematically searched until May 04, 2023. Studies that evaluated the predictors of pacemaker requirement in patients with implantable loop recorder and unexplained syncope were included. The "Quality In Prognosis Studies" appraisal tool was used for quality assessment. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated. The publication bias was evaluated using Egger's and Begg's tests. Ten studies (n = 4200) were included. Right bundle branch block (OR: 3.264; 95% CI: 1.907-5.588, p < .0001) and bifascicular block (OR: 2.969; 95% CI: 1.859-4.742, p < .0001) were the strongest predictors for pacemaker implantation. Pacemaker requirement was more than two times in patients with atrial fibrillation, sinus bradycardia and first degree AV block. Valvular heart disease, diabetes mellitus, and hypertension were also significantly more in patients with pacemaker implantation. Age (standardized mean difference [SMD]: 0.560; 95% CI: 0.410/0.710, p < .0001) and PR interval (SMD: 0.351; 95% CI: 0.150/0.553, p = .001) were significantly higher in patients with pacemaker requirement. Heart conduction disorders, atrial arrhythmias and underlying medical conditions are main predictors of pacemaker device implantation following loop recorder installation in unexplained syncopal patients.

Associations between short-term exposure to fine particulate matter and acute myocardial infarction: A case-crossover study.

BACKGROUND: Previous studies evaluated the impact of particle matters (PM) on the risk of acute myocardial infarction (AMI) based on local registries. HYPOTHESIS: This study aimed to evaluate possible short term effect of air pollutants on occurrence of AMI based on a specific case report sheet that was designed for this purpose. METHODS: AMI was documented among 982 patients who referred to the emergency departments in Tehran, Iran, between July 2017 to March 2019. For each patient, case period was defined as 24 hour period preceding the time of emergency admission and referent periods were defined as the corresponding time in 1, 2, and 3 weeks before the admission. The associations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2 .5 ) and particulate matter with an aerodynamic diameter ≤10 µm (PM10 ) with AMI were analyzed using conditional logistic regression in a case-crossover design. RESULT: Increase in PM2.5 and PM10 was significantly associated with the occurrence of AMI with and without adjustment for the temperature and humidity. In the adjusted model each 10 µg/m3 increase of PM10 and PM2.5 in case periods was significantly associated with increase myocardial infarction events (95% CI = 1.041-1.099, OR = 1.069 and 95% CI = 1.073-1.196, and OR = 1.133, respectively). Subgroup analysis showed that increase in PM10 did not increase AMI events in diabetic subgroup, but in all other subgroups PM10 and PM2 .5 concentration showed positive associations with increased AMI events. CONCLUSION: Acute exposure to ambient air pollution was associated with increased risk of AMI irrespective of temperature and humidity.

Estimating Compressive Strength of Concrete Using Neural Electromagnetic Field Optimization.

Concrete compressive strength (CCS) is among the most important mechanical characteristics of this widely used material. This study develops a novel integrative method for efficient prediction of CCS. The suggested method is an artificial neural network (ANN) favorably tuned by electromagnetic field optimization (EFO). The EFO simulates a physics-based strategy, which in this work is employed to find the best contribution of the concrete parameters (i.e., cement (C), blast furnace slag (SBF), fly ash (FA1), water (W), superplasticizer (SP), coarse aggregate (AC), fine aggregate (FA2), and the age of testing (AT)) to the CCS. The same effort is carried out by three benchmark optimizers, namely the water cycle algorithm (WCA), sine cosine algorithm (SCA), and cuttlefish optimization algorithm (CFOA) to be compared with the EFO. The results show that hybridizing the ANN using the mentioned algorithms led to reliable approaches for predicting the CCS. However, comparative analysis indicates that there are appreciable distinctions between the prediction capacity of the ANNs created by the EFO and WCA vs. the SCA and CFOA. For example, the mean absolute error calculated for the testing phase of the ANN-WCA, ANN-SCA, ANN-CFOA, and ANN-EFO was 5.8363, 7.8248, 7.6538, and 5.6236, respectively. Moreover, the EFO was considerably faster than the other strategies. In short, the ANN-EFO is a highly efficient hybrid model, and can be recommended for the early prediction of the CCS. A user-friendly explainable and explicit predictive formula is also derived for the convenient estimation of the CCS.

Aortic dissection and Covid-19; a comprehensive systematic review.

Coronavirus disease 19 (Covid-19) has been declared as a pandemic disease since March 2020; causing wide array of signs and symptoms, many of which result in increased mortality rates worldwide. Although it was initially known as an acute respiratory disease, Covid-19 is accompanied with several extrapulmonary manifestations, of which the cardiovascular ones are of major importance. Among other cardiovascular complications of Covid-19, aortic dissection has been a significant yet underrated problem. The pathophysiology of aortic dissection consists of various inflammatory pathways, that could be influenced by Covid-19 infection. We herein have reviewed articles inclusive of aortic dissection concurrent with Covid-19 infection in a systematic manner, along with the probable similarities in pathophysiology of aortic dissection with Covid-19 infection.

25-Hydroxy Vitamin D Level and Its Correlation with Mean Platelet Volume in Preeclampsia.

Background: Preeclampsia is one of the challenging complications of pregnancy, of which little is known about its etiology and pathogenesis. Many studies have shown higher mean platelet volume (MPV) in preeclamptic patients. Vitamin D deficiency is in association with larger-size platelets. Thus, we aimed to determine the correlation of vitamin D with MPV in preeclamptic patients. Methods: This prospective case-control study was conducted in two tertiary hospitals in Tehran, Iran. Overall, 85 preeclamptic pregnant women and 85 normotensive pregnant women were entered between 2017 and 2018. Serum vitamin D concentration (ng/ml) and MPV (femtoliter) were measured for all patients. Results: MPV was significantly higher in the cases compared to controls (10.59±1.08 vs 8.10±0.95, P=0.0001). In addition, serum vitamin D level in the preeclamptic group was significantly lower in compare to the control group (17.79±11.03 vs 30.24±12.49; P=0.0001). In multivariate logistic regression analysis, high age of mother (OR: 1.13; 95% CI: 1.01-1.27; P=0.03), low level of serum vitamin D (OR: 0.93; 95% CI: 0.87-0.99; P=0.02) and high MPV (OR: 8.83; 95% CI: 4.17-18.67; P=0.0001) were independent predictors of preeclampsia. Moreover, a correlation analysis revealed that vitamin D levels correlated negatively with MPV (r= -0.41, P<0.0001). Conclusion: Low levels of vitamin D in preeclamptic pregnancy are associated with higher platelet activity and thrombosis. In fact, the increment of MPV level might be a potential pathway for adverse outcomes of pregnancy including preeclampsia in the context of vitamin D deficiency.

How to improve information technology strategic planning effectiveness using balanced scorecard, risk and maturity analysis, case study health information technology? A qualitative study.

Background and Aims: Although many health strategic plans have been developed by scholars and organizations, they still suffer from a limited view. Since most health-related strategies in the future will depend on information technology (IT), as the main driver of today's industry, technology, and society, IT merits attention in health strategic plans. While the majority of the health strategic plan developed based on the interviews and questioner and these plans didn't consider the role of IT in their actions, this research will develop a framework to integrate risk and maturity analysis with the strategic planning process in health information technology strategic plan. Methods: The present research introduces an integrated framework based on a balanced scorecard (BSC) and control objectives for information and related technologies (COBIT). Also, The American Productivity & Quality Centre framework and COBIT were employed in this model to define the processes and activities of health IT (HIT) organizations. The organization's maturity and risk are analyzed in terms of information and management criteria using BSC, COBIT, and the analytical hierarchy process. Results: Later this model was implemented in a Remote Health care System to improve the strategic management process for this technology. Using this framework, 17 business goals have been developed and presented for the case. Also, the total related risk was 48% and the maturity level was at 1/18. The results are presented as decision-making parameters and strategies for successful IT implementation. Conclusion: The presented framework provides deeper insight for the decision-maker through integrating risk and maturity analysis in the HIT strategic planning process. The results are presented as decision-making parameters and strategies for successful IT implementation. These strategies help investors decide about resource allocation based on the risk-taking capability, certainty, and uncertainty results of the plan.

The association between QTc, QTd, TPE, and fragmented QRS before and after PPCI with hospital mortality in STEMI patients.

INTRODUCTION: ST-elevation myocardial infarction (STEMI) is known to be associated with significant arrhythmia and consequent mortality. QT prolongation is a risk factor for arrhythmia in STEMI patients who underwent primary percutaneous coronary intervention (PPCI). The aim of this investigation was to evaluate the association of corrected QT interval (QTc), QT dispersion (QTd), T-wave peak to end (TPE), and fragmented QRS with mortality in these patients. METHODS: Eligible patients with the characteristic symptoms of STEMI who underwent PPCI were included. QTc, QTd, TPE, and fragmented QRS were measured before and after the PPCI. These predictors were compared between patients who died during hospitalization and discharged patients. RESULTS: After coronary angiography, 10 patients (4%) died during the hospitalization after PPCI. Comparing the non-survivers and discharged patients in terms of arrhythmia predictors showed that the mean QT dispersion and TPE before intervention were significantly higher in the non-survivors. Also, the number of patients who experienced fragmented QRS both before and after the intervention was significantly higher in the non-survivors. CONCLUSION: These data suggested that evaluating such arrhythmia predictors, especially before PPCI, could be used as a predictor of mortality in STEMI patients who underwent PPCI.

Is COVID-19 really a geriatric syndrome?

Geriatric syndromes are a group of medical conditions, such as cognitive impairment, delirium, frailty, dizziness, syncope, and incontinence, associated with age increase. Many studies have reported a higher mortality rate for older COVID-19 patients, which could be explained by the complications of COVID-19, including the components of geriatric syndromes. We read with great interest the paper "Prevalence of unwillingness and uncertainty to vaccinate against COVID-19 in older people: A systematic review and meta-analysis" by Nicola Veronese et al. Their valuable work determines how uncertainty and unwillingness towards receiving the COVID-19 vaccine are more prevalent among older adults and how this hesitancy could affect vaccine uptake, and ultimately, the mortality rate. Regarding this paper, we wish to address some points.

The Pseudo-Natural Product Rhonin Targets RHOGDI.

For the discovery of novel chemical matter generally endowed with bioactivity, strategies may be particularly efficient that combine previous insight about biological relevance, e.g., natural product (NP) structure, with methods that enable efficient coverage of chemical space, such as fragment-based design. We describe the de novo combination of different 5-membered NP-derived N-heteroatom fragments to structurally unprecedented "pseudo-natural products" in an efficient complexity-generating and enantioselective one-pot synthesis sequence. The pseudo-NPs inherit characteristic elements of NP structure but occupy areas of chemical space not covered by NP-derived chemotypes, and may have novel biological targets. Investigation of the pseudo-NPs in unbiased phenotypic assays and target identification led to the discovery of the first small-molecule ligand of the RHO GDP-dissociation inhibitor 1 (RHOGDI1), termed Rhonin. Rhonin inhibits the binding of the RHOGDI1 chaperone to GDP-bound RHO GTPases and alters the subcellular localization of RHO GTPases.

Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate Cells.

Embryonic stem cell-expressed Ras (ERas) is an atypical constitutively active member of the Ras family and controls distinct signaling pathways, which are critical, for instance, for the maintenance of quiescent hepatic stellate cells (HSCs). Unlike classical Ras paralogs, ERas has a unique N-terminal extension (Nex) with as yet unknown function. In this study, we employed affinity pull-down and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses and identified 76 novel binding proteins for human and rat ERas Nex peptides, localized in different subcellular compartments and involved in various cellular processes. One of the identified Nex-binding proteins is the nonmitochondrial, cytosolic arginase 1 (ARG1), a key enzyme of the urea cycle and involved in the de novo synthesis of polyamines, such as spermidine and spermine. Here, we show, for the first time, a high-affinity interaction between ERas Nex and purified ARG1 as well as their subcellular colocalization. The inhibition of ARG1 activity strikingly accelerates the activation of HSCs ex vivo, suggesting a central role of ARG1 activity in the maintenance of HSC quiescence.

Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds.

In phenotypic compound discovery, conclusive identification of cellular targets and mode of action are often impaired by off-target binding. In particular, microtubules are frequently targeted in cellular assays. However, in vitro tubulin binding assays do not correctly reflect the cellular context, and conclusive high-throughput phenotypic assays monitoring tubulin binding are scarce, such that tubulin binding is rarely identified. We report that morphological profiling using the Cell Painting assay (CPA) can efficiently detect tubulin modulators in compound collections with a high throughput, including annotated reference compounds and unannotated compound classes with unrelated chemotypes and scaffolds. Small-molecule tubulin binders share similar CPA fingerprints, which enables prediction and experimental validation of microtubule-binding activity. Our findings suggest that CPA or a related morphological profiling approach will be an invaluable addition to small-molecule discovery programs in chemical biology and medicinal chemistry, enabling early identification of one of the most frequently observed off-target activities.

Inhibition of the RacGEF VAV3 by the small molecule IODVA1 impedes RAC signaling and overcomes resistance to tyrosine kinase inhibition in acute lymphoblastic leukemia.

Aberrant RHO guanine nucleotide exchange factor (RhoGEF) activation is chief mechanism driving abnormal activation of their GTPase targets in transformation and tumorigenesis. Consequently, a small-molecule inhibitor of RhoGEF can make an anti-cancer drug. We used cellular, mouse, and humanized models of RAC-dependent BCR-ABL1-driven and Ph-like acute lymphoblastic leukemia to identify VAV3, a tyrosine phosphorylation-dependent RacGEF, as the target of the small molecule IODVA1. We show that through binding to VAV3, IODVA1 inhibits RAC activation and signaling and increases pro-apoptotic activity in BCR-ABL1-transformed cells. Consistent with this mechanism of action, cellular and animal models of BCR-ABL1-induced leukemia in Vav3-null background do not respond to IODVA1. By durably decreasing in vivo RAC signaling, IODVA1 eradicates leukemic propagating activity of TKI-resistant BCR-ABL1(T315I) B-ALL cells after treatment withdrawal. Importantly, IODVA1 suppresses the leukemic burden in the treatment refractory pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models better than standard-of-care dasatinib or ponatinib and provides a more durable response after treatment withdrawal. Pediatric leukemia samples with diverse genetic lesions show high sensitivity to IODVA1 ex vivo and this sensitivity is VAV3 dependent. IODVA1 thus spearheads a novel class of drugs that inhibits a RacGEF and holds promise as an anti-tumor therapy.

Selective inhibition of IL-6 trans-signaling by a miniaturized, optimized chimeric soluble gp130 inhibits TH17 cell expansion.

The cytokine interleukin-6 (IL-6) signals through three mechanisms called classic signaling, trans-signaling, and trans-presentation. IL-6 trans-signaling is distinctly mediated through a soluble form of its transmembrane receptor IL-6R (sIL-6R) and the coreceptor gp130 and is implicated in multiple autoimmune diseases. Although a soluble form of gp130 (sgp130) inhibits only IL-6 trans-signaling, it also blocks an analogous trans-signaling mechanism of IL-11 and its soluble receptor sIL-11R. Here, we report miniaturized chimeric soluble gp130 variants that efficiently trap IL-6:sIL-6R but not IL-11:sIL-11R complexes. We designed a novel IL-6 trans-signaling trap by fusing a miniaturized sgp130 variant to an IL-6:sIL-6R complex-binding nanobody and the Fc portion of immunoglobulin G (IgG). This trap, called cs-130Fc, exhibited improved inhibition of as well as increased selectivity for IL-6 trans-signaling compared to the conventional fusion protein sgp130Fc. We introduced affinity-enhancing mutations in cs-130Fc and sgp130Fc that further improved selectivity toward IL-6 trans-signaling. Moreover, cs-130Fc efficiently inhibited the expansion of T helper 17 (TH17) cells in cultures of mouse CD4+ T cells treated with IL-6:sIL-6R. Thus, these variants may provide or lead to the development of more precisely targeted therapeutics for inflammatory disorders associated with IL-6 trans-signaling.

Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: Results of a multicenter national survey.

BACKGROUND: There are some data showing that repurposed drugs used for the Coronavirus disease-19 (COVID-19) have potential to increase the risk of QTc prolongation and torsade de pointes (TdP), and these arrhythmic side effects have not been adequately addressed in COVID-19 patients treated with these repurposed medications. METHODS: This is the prospective study of 2403 patients hospitalised at 13 hospitals within the COVID-19 epicentres of the Iran. These patients were treated with chloroquine, hydroxychloroquine, lopinavir/ritonavir, atazanavir/ritonavir, oseltamivir, favipiravir and remdesivir alone or in combination with azithromycin. The primary outcome of the study was incidence of critical QTc prolongation, and secondary outcomes were incidences of TdP and death. RESULTS: Of the 2403 patients, 2365 met inclusion criteria. The primary outcome of QTc ≥ 500 ms and ∆QTc ≥ 60 ms was observed in 11.2% and 17.6% of the patients, respectively. The secondary outcomes of TdP and death were reported in 0.38% and 9.8% of the patients, respectively. The risk of critical QT prolongation increased in the presence of female gender, history of heart failure, treatment with hydroxychloroquine, azithromycin combination therapy, simultaneous furosemide or beta-blocker therapy and acute renal or hepatic dysfunction. However, the risk of TdP was predicted by treatment with lopinavir-ritonavir, simultaneous amiodarone or furosemide administration and hypokalaemia during treatment. CONCLUSION: This cohort showed significant QTc prolongation with all COVID-19 medications studied, however, life-threatening arrhythmia of TdP occurred rarely. Among the repurposed drugs studied, hydroxychloroquine or lopinavir-ritonavir alone or in combination with azithromycin clearly demonstrated to increase the risk of critical QT prolongation and/or TdP.

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

BACKGROUND: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. METHODS: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. CONCLUSION: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Acute type A aortic dissection in a patient with COVID-19.

The novel coronavirus spread all over the world in 2019 and became a serious international health concern of this century. Coronavirus disease 2019 (COVID-19) had a wide range of clinical manifestations; it can cause mild-to-severe multiorgan diseases, mostly affecting the respiratory system, but cardiovascular symptoms and complications are also frequently presented in COVID-19 patients. Herein, we report a type A aortic dissection in a confirmed case of COVID-19.

Air Pollution and Cardiac Arrhythmias: A Comprehensive Review.

Air pollution is the mixture of some chemical and environmental agents including dust, fumes, gases, particulate matters, and biological materials which can be harmful for the environment and the human body. The increasing trend of the air pollution, especially in developing countries, may exert its detrimental effects on human health. The potentially harmful effects of air pollution on the human health have been recognized and many epidemiological studies have clearly suggested the strong association between air pollution exposure and increased morbidities and mortalities. Air pollutants are classified into gaseous pollutants including carbon mono oxide, nitrogen oxides, ozone and sulfur dioxide, and particulate matters (PMs). All air pollutants have destructive effects on the health systems including cardiovascular system. Many studies have demonstrated the effect of air pollutant on the occurrence of ST elevation myocardial infarction, sudden cardiac death, cardiac arrythmias, and peripheral arterial disease. Recently, some studies suggested that air pollution may be associated with cardiac arrhythmias. In this study, we aimed to comprehensively review the last evidences related to the association of air pollutant and cardiac arrythmias. We found that particulate matters (PM10, PM2.5, and UFP) and gaseous air pollutants can exert undesirable effects on cardiac rhythms. Short-term and long-term exposure to the air pollutants can interact with the cardiac rhythms through oxidative stress, autonomic dysfunction, coagulation dysfunction, and inflammation. It seems that particulate matters, especially PM2.5 have stronger association with cardiac arrhythmias among all air pollutants. However, future studies are needed to confirm these results.