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1.
Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function.
Laurila, S, Rebelos, E, Lahesmaa, M, Sun, L, Schnabl, K, Peltomaa, TM, Klén, R, U-Din, M, Honka, MJ, Eskola, O, et al
American journal of physiology. Endocrinology and metabolism. 2022;(1):E54-E62
Abstract
The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography. Kidney function was measured with [18F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared with placebo (secretin vs. placebo, means ± SD, 15.5 ± 7.4 vs. 9.7 ± 4.9 μmol/100 g/min, 95% confidence interval (CI) [2.2, 9.4], P = 0.004). Secretin also increased [18F]FDG renal clearance (44.5 ± 5.4 vs. 39.5 ± 8.5 mL/min, 95%CI [1.9, 8.1], P = 0.004), and eGFR was significantly increased from baseline after secretin, compared with placebo (17.8 ± 9.8 vs. 6.0 ± 5.2 ΔmL/min/1.73 m2, 95%CI [6.0, 17.6], P = 0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.NEW & NOTEWORTHY Secretin increases myocardial glucose uptake compared with placebo, supporting a previously proposed inotropic effect. Secretin also increased renal filtration rate.
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2.
The effect of exercise on left ventricular global longitudinal strain.
Murray, J, Bennett, H, Bezak, E, Perry, R, Boyle, T
European journal of applied physiology. 2022;(6):1397-1408
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Abstract
Exercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre-post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59; 95% CI 0.16-1.02; p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed.
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Altered cardiac reserve is a determinant of exercise intolerance in sickle cell anaemia patients.
Hammoudi, N, Ceccaldi, A, Haymann, JP, Guedeney, P, Nicolas-Jilwan, F, Zeitouni, M, Montalescot, G, Lionnet, F, Isnard, R, Hatem, SN
European journal of clinical investigation. 2022;(1):e13664
Abstract
BACKGROUND The underlying mechanisms of exercise intolerance in sickle cell anaemia (SCA) patients are complex and not yet completely understood. While latent heart failure at rest could be unmasked upon exercise, most previous studies assessed cardiac function at rest. We aimed to investigate exercise cardiovascular reserve as a potential contributor to exercise intolerance in adult SCA patients. METHODS In this observational prospective study, we compared prospectively 60 SCA patients (median age 31 years, 60% women) to 20 matched controls. All subjects underwent symptom-limited combined exercise echocardiography and oxygen uptake (VO2 ) measurements. Differences between arterial and venous oxygen content (C(a-v)O2 ) were calculated. Cardiac reserve was defined as the absolute change in cardiac index (Ci) from baseline to peak exercise. RESULTS Compared to controls, SCA patients demonstrated severe exercise intolerance (median peakVO2 , 34.3 vs. 19.7 ml/min/kg, respectively, p < .0001). SCA patients displayed heterogeneously increased Ci from rest to peak exercise (median +5.8, range 2.6 to 10.6 L/min/m²) which correlated with peakVO2 (r = 0.71, p < .0001). In contrast, the C(a-v)O2 exercise reserve was homogenously reduced and did not correlate with peakVO2 (r = 0.18, p = .16). While haemoglobin level and C(a-v)O2 were similar in SCA subgroups, SCA patients in the lower VO2 tertile had chronotropic incompetence and left ventricular diastolic dysfunction (left atrial peak longitudinal strain was reduced, and both E/e' ratio and left atrial volume index were increased) and were characterized by a reduced cardiac reserve, +5.0[4.2-5.5] compared to +6.7[5.5-7.8] L/min/m² for the rest of the patient cohort, p < .0001. CONCLUSIONS Altered cardiac reserve due to chronotropic incompetence and left ventricular diastolic dysfunction seems to be an important determinant of exercise intolerance in adult SCA patients.
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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.