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An observational study on the effect of hypercholesterolemia developed after living donor liver transplantation on cardiac event and graft failure.
Park, J, Lee, SH, Han, S, Oh, AR, Lee, SK, Choi, GS, Park, MS, Carriere, K, Ahn, J, Kim, GS
Scientific reports. 2021;(1):959
Abstract
This study sought to evaluate the association between newly-developed significant hypercholesterolemia within one year following living donor liver transplantation (LDLT) and long term outcomes in light of cardiovascular events and graft failure. From October 2003 to July 2017, 877 LDLT recipients were stratified according to development of significant hypercholesterolemia within one year following LDLT. The primary outcome was occurrence of a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and coronary revascularization after LDLT. The incidence of graft failure, defined as all-cause death or retransplantation, was also compared. A total of 113 (12.9%) recipients developed significant hypercholesterolemia within one year. The differences in incidences of cardiac related events and graft related events began emerging significantly higher in the hypercholesterolemia group after 24 months and 60 months since the LDLT, respectively. After adjustment using the inverse probability of weighting, the hazard ratio (HR) for MACE was 2.77 (95% confidence interval (CI) 1.16-6.61; p = 0.02), while that for graft failure was 3.76 (95% CI 1.97-7.17, p < 0.001). A significant hypercholesterolemia after LDLT may be associated with cardiac and graft-related outcome; therefore, a further study and close monitoring of cholesterol level after LDLT is needed.
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Multi-scale approaches for the simulation of cardiac electrophysiology: I - Sub-cellular and stochastic calcium dynamics from cell to organ.
Colman, MA, Holmes, M, Whittaker, DG, Jayasinghe, I, Benson, AP
Methods (San Diego, Calif.). 2021;:49-59
Abstract
Computational models of the heart at multiple spatial scales, from sub-cellular nanodomains to the whole-organ, are a powerful tool for the simulation of cardiac electrophysiology. Application of these models has provided remarkable insight into the normal and pathological functioning of the heart. In these two articles, we present methods for modelling cardiac electrophysiology at all of these spatial scales. In part one, presented here, we discuss methods and approaches for modelling sub-cellular calcium dynamics at the whole-cell and organ scales, valuable for modelling excitation-contraction coupling and mechanisms of arrhythmia triggers.
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The role of iron in doxorubicin-induced cardiotoxicity: recent advances and implication for drug delivery.
Qin, Y, Guo, T, Wang, Z, Zhao, Y
Journal of materials chemistry. B. 2021;(24):4793-4803
Abstract
As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for treating various types of tumors. Unfortunately, the clinical application of this drug results in severe side effects, particularly dose-dependent cardiotoxicity. There are multiple mechanisms involved with the cardiotoxicity caused by DOX, among which intracellular iron homeostasis plays an essential role based on a recent discovery. In this mini-review, we summarize the clinical features and symptoms of DOX-dependent cardiotoxicity, discuss the correlation between iron and cardiotoxicity, and highlight the involvement of iron-dependent ferroptotic cell death therein. Recent advances in this topic will aid the development of novel DOX delivery systems with reduced adverse effects, and expand the clinical application of anthracycline.
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Practical instructions for using drugs in CT and MR cardiac imaging.
Rovere, G, Meduri, A, Savino, G, Flammia, FC, Lo Piccolo, F, Carafa, MRP, Larici, AR, Natale, L, Merlino, B, Marano, R
La Radiologia medica. 2021;(3):356-364
Abstract
The progressive increase in numbers of noninvasive cardiac imaging examinations broadens the spectrum of knowledge radiologists are expected to acquire in the management of drugs during CT coronary angiography (CTCA) and cardiac MR (CMR) to improve image quality for optimal visualization and assessment of the coronary arteries and adequate MR functional analysis. Aim of this review is to provide an overview on different class of drugs (nitrate, beta-blockers, ivabradine, anxiolytic, adenosine, dobutamine, atropine, dipyridamole and regadenoson) that can be used in CTCA and CMR, illustrating their main indications, contraindications, efficacy, mechanism of action, metabolism, safety, side effects or complications, and providing advices in their use.
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Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development.
Lionetti, V, Bollini, S, Coppini, R, Gerbino, A, Ghigo, A, Iaccarino, G, Madonna, R, Mangiacapra, F, Miragoli, M, Moccia, F, et al
Pharmacological research. 2021;:105581
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Abstract
In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches.
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Prognostic usefulness of planar 123I-MIBG scintigraphic images of myocardial sympathetic innervation in congestive heart failure: Follow-Up data from ADMIRE-HF.
Agostini, D, Ananthasubramaniam, K, Chandna, H, Friberg, L, Hudnut, A, Koren, M, Miyamoto, MI, Senior, R, Shah, M, Travin, MI, et al
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2021;(4):1490-1503
Abstract
BACKGROUND To evaluate whether planar 123I-MIBG myocardial scintigraphy predicts risk of death in heart failure (HF) patients up to 5 years after imaging. METHODS AND RESULTS Subjects from ADMIRE-HF were followed for approximately 5 years after imaging (964 subjects, median follow-up 62.7 months). Subjects were stratified according to the heart/mediastinum (H/M) ratio (< 1.60 vs ≥ 1.60) on planar 123I-MIBG scintigraphic images obtained at baseline in ADMIRE-HF. Cox proportional hazards models and Kaplan-Meier analyses were used to evaluate time to death, cardiac death, or arrhythmic events for subjects stratified by H/M ratio, baseline left ventricular ejection fraction (LVEF: < 25% and 25 to ≤ 35%), and by H/M strata within LVEF strata. All-cause mortality was 38.4% vs 20.9% and cardiac mortality was 16.8% vs 4.5%, in subjects with H/M < 1.60 vs ≥ 1.60, respectively (P < 0.05 for both comparisons). Subjects with preserved sympathetic innervation of the myocardium (H/M ≥ 1.60) were at significantly lower risk of all-cause and cardiac death, arrhythmic events, sudden cardiac death, or potentially life-threatening arrhythmias. Within LVEF strata, a trend toward a higher mortality for subjects with H/M < 1.60 was observed reaching significance for LVEF 25 to ≤ 35% only. CONCLUSIONS During a median follow-up of 62.7 months, patients with H/M ≥ 1.60 were at significantly lower risk of death and arrhythmic events independently of LVEF values.
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Cardiotoxicity of Radiation Therapy: Mechanisms, Management, and Mitigation.
Ell, P, Martin, JM, Cehic, DA, Ngo, DTM, Sverdlov, AL
Current treatment options in oncology. 2021;(8):70
Abstract
Radiation therapy is a key component of modern-day cancer therapy and can reduce the rates of recurrence and death from cancer. However, it can increase risk of cardiovascular (CV) events, and our understanding of the timeline associated with that risk is shorter than previously thought. Risk mitigation strategies, such as different positioning techniques, and breath hold acquisitions as well as baseline cardiovascular risk stratification that can be undertaken at the time of radiotherapy planning should be implemented, particularly for patients receiving chest radiation therapy. Primary and secondary prevention of cardiovascular disease (CVD), as appropriate, should be used before, during, and after radiation treatment in order to minimize the risks. Opportunistic screening for subclinical coronary disease provides an attractive possibility for primary/secondary CVD prevention and thus mitigation of long-term CV risk. More data on long-term clinical usefulness of this strategy and development of appropriate management pathways would further strengthen the evidence for the implementation of such screening. Clear guidelines in initial cardiovascular screening and cardiac aftercare following radiotherapy need to be formulated in order to integrate these measures into everyday clinical practice and policy and subsequently improve post-treatment morbidity and mortality for these patients.
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Multi-scale approaches for the simulation of cardiac electrophysiology: II - Tissue-level structure and function.
Benson, AP, Stevenson-Cocks, HJ, Whittaker, DG, White, E, Colman, MA
Methods (San Diego, Calif.). 2021;:60-81
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Abstract
Computational models of the heart, from cell-level models, through one-, two- and three-dimensional tissue-level simplifications, to biophysically-detailed three-dimensional models of the ventricles, atria or whole heart, allow the simulation of excitation and propagation of this excitation, and have provided remarkable insight into the normal and pathological functioning of the heart. In this article we present equations for modelling cellular excitation (i.e. the cell action potential) from both a phenomenological and a biophysical perspective. Hodgkin-Huxley formalism is discussed, along with the current generation of biophysically-detailed cardiac cell models. Alternative Markovian formulations for modelling ionic currents are also presented. Equations describing propagation of this cellular excitation, through one-, two- and three-dimensional idealised or realistic tissues, are then presented. For all types of model, from cell to tissue, methods for discretisation and integration of the underlying equations are discussed. The article finishes with a discussion of two tissue-level experimental imaging techniques - diffusion tensor magnetic resonance imaging and optical imaging - that can be used to provide data for parameterisation and validation of cell- and tissue-level cardiac models.
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Empagliflozin Treatment Is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes.
Thirunavukarasu, S, Jex, N, Chowdhary, A, Hassan, IU, Straw, S, Craven, TP, Gorecka, M, Broadbent, D, Swoboda, P, Witte, KK, et al
Diabetes. 2021;(12):2810-2822
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Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and 31P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and 31P-MRS scans before and after 12 weeks' empagliflozin treatment. Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycemic control underwent an identical scan protocol at a single visit. Empagliflozin treatment was associated with significant improvements in phosphocreatine-to-ATP ratio (1.52 to 1.76, P = 0.009). This was accompanied by a 7% absolute increase in the mean left ventricular ejection fraction (P = 0.001), 3% absolute increase in the mean global longitudinal strain (P = 0.01), 8 mL/m2 absolute reduction in the mean myocardial cell volume (P = 0.04), and 61% relative reduction in the mean NT-proBNP (P = 0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected. Empagliflozin thus ameliorates the "cardiac energy-deficient" state, regresses adverse myocardial cellular remodeling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate HF in T2D.
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High Fasting Glycemia Predicts Impairment of Cardiac Autonomic Control in Adults With Type 2 Diabetes: A Case-Control Study.
Silva, LRB, Gentil, P, Seguro, CS, de Oliveira, GT, Silva, MS, Zamunér, AR, Beltrame, T, Rebelo, ACS
Frontiers in endocrinology. 2021;:760292
Abstract
INTRODUCTION Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes. OBJECTIVE To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements. MATERIALS AND METHODS This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR. RESULTS At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D. CONCLUSION Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.