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Pubblicazioni recenti - cardiorenal
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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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Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Markers of Vascular Damage.
J Pers Med2023 Mar;13(3):. doi: 536.
Kourtidou Christodoula, Rafailidis Vasileios, Varouktsi Garyfallia, Kanakis Efthimios, Liakopoulos Vassilios, Vyzantiadis Timoleon-Achilleas, Savopoulos Christos, Marinaki Smaragdi, Stangou Maria, Tziomalos Konstantinos,
Abstract
BACKGROUND:
Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular morbidity and delay the progression of kidney disease in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms underpinning these benefits are not entirely clear. More specifically, it is uncertain whether these agents exert cardiorenal protective effects through a direct action on the vascular wall. The aim of the present study was to evaluate the effects of SGLT2 inhibitors on markers of subclinical vascular damage.
METHODS:
In total, 40 adult patients with T2DM and glomerular filtration rate (GFR) 60 mL/min/1.73 m were consecutively enrolled. Indices of arterial stiffness (pulse wave velocity, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (Alx@75) and central systolic, diastolic, pulse and mean pressure), carotid atherosclerosis (stenosis, intima-media thickness (cIMT) and maximal plaque thickness) and peripheral arterial disease (ankle brachial index (ABI)) were determined. The chi-squared and Mann-Whitney U-test were used to detect differences in categorical and continuous variables between groups, respectively.
RESULTS:
In total, 15 patients were treated with SGLT2 inhibitors and 25 patients were not receiving these agents. Serum low-density lipoprotein cholesterol levels were lower in the former whereas other cardiovascular risk factors, the prevalence of established cardiovascular disease, anthropometric and demographic characteristics, and vital signs did not differ between the 2 groups. The AIx was lower in patients treated with SGLT2 inhibitors (21.9 ± 11.3 vs. 29.7 ± 12% in patients not treated with SGLT2 inhibitors;
CONCLUSIONS:
Treatment with SGLT2 inhibitors appears to reduce arterial stiffness. Accordingly, these agents might improve cardiovascular outcomes not only in patients with T2DM and established cardiorenal disease but also in lower-risk patients.
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Data Analysis of Impaired Renal and Cardiac Function Using a Combination of Standard Classifiers.
J Pers Med2023 Feb;13(3):. doi: 437.
Tasic Danijela, Furundzic Drasko, Djordjevic Katarina, Galovic Slobodanka, Dimitrijevic Zorica, Radenkovic Sonja,
Abstract
We examine the significance of the predictive potential of EPI cystatin C (EPI CysC) in combination with NTproBNP, sodium, and potassium in the evaluation of renal function in patients with cardiorenal syndrome using standard mathematical classification models from the domain of artificial intelligence. The criterion for the inclusion of subjects with combined impairment of heart and kidney function in the study was the presence of newly discovered or previously diagnosed clinically manifest cardiovascular disease and acute or chronic kidney disease in different stages of evolution. In this paper, five standard classifiers from the field of machine learning were used for the analysis of the obtained data: ensemble of neural networks (MLP), ensemble of -nearest neighbors (-NN) and naive Bayes classifier, decision tree, and a classifier based on logistic regression. The results showed that in MLP, -NN, and naive Bayes, EPI CysC had the highest predictive potential. Thus, our approach with utility classifiers recognizes the essence of the disorder in patients with cardiorenal syndrome and facilitates the planning of further treatment.
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Characteristics of Patients with Heart Failure and Advanced Chronic Kidney Disease (Stages 4-5) Not Undergoing Renal Replacement Therapy (ERCA-IC Study).
J Clin Med2023 Mar;12(6):. doi: 2339.
Valdivielso Moré Sandra, Vicente Elcano Miren, García Alonso Anna, Pascual Sanchez Sergi, Galceran Herrera Isabel, Barbosa Puig Francesc, Belarte-Tornero Laia C, Ruiz-Bustillo Sonia, Morales Murillo Ronald O, Barrios Clara, Vime-Jubany Joan, Farre Nuria,
Abstract
BACKGROUND:
Despite the frequent coexistence of heart failure (HF) in patients with advanced chronic kidney disease (CKD), it has been understudied, and little is known about its prevalence and prognostic relevance.
METHODS:
retrospective study of 217 patients with advanced CKD (stages 4 and 5) who did not undergo renal replacement therapy (RRT). The patients were followed up for two years. The primary outcome was all-cause death or the need for RRT.
RESULTS:
Forty percent of patients had a history of HF. The mean age was 78.2 ± 8.8 years and the mean eGFR was 18.4 ± 5.5 mL/min/1.73 m. The presence of previous HF identified a subgroup of high-risk patients with a high prevalence of cardiovascular comorbidities and was significantly associated with the composite endpoint of all-cause hospitalization or need for RRT (66.7% vs. 53.1%, HR 95% CI 1.62 (1.04-2.52), = 0.034). No differences were found in the need for RRT (27.6% vs. 32.2%, = 0.46). Nineteen patients without HF at baseline developed HF during the follow-up and all-cause death was numerically higher (36.8 vs. 19.8%, = 0.1).
CONCLUSIONS:
Patients with advanced CKD have a high prevalence of HF. The presence of previous HF identified a high-risk population with a worse prognosis that required close follow-up.
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A Role of Sodium-Glucose Co-Transporter 2 in Cardiorenal Anemia Iron Deficiency Syndrome.
Int J Mol Sci2023 Mar;24(6):. doi: 5983.
Sano Motoaki,
Abstract
Heart failure, renal dysfunction, anemia, and iron deficiency affect each other and form a vicious cycle, a condition referred to as cardiorenal anemia iron deficiency syndrome. The presence of diabetes further accelerates this vicious cycle. Surprisingly, simply inhibiting sodium-glucose co-transporter 2 (SGLT2), which is expressed almost exclusively in the proximal tubular epithelial cells of the kidney, not only increases glucose excretion into the urine and effectively controls blood glucose levels in diabetes but can also correct the vicious cycle of cardiorenal anemia iron deficiency syndrome. This review describes how SGLT2 is involved in energy metabolism regulation, hemodynamics (i.e., circulating blood volume and sympathetic nervous system activity), erythropoiesis, iron bioavailability, and inflammatory set points in diabetes, heart failure, and renal dysfunction.
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The Effect of Aldosterone on Cardiorenal and Metabolic Systems.
Int J Mol Sci2023 Mar;24(6):. doi: 5370.
Otsuka Hiromasa, Abe Masanori, Kobayashi Hiroki,
Abstract
Aldosterone, a vital hormone of the human body, has various pathophysiological roles. The excess of aldosterone, also known as primary aldosteronism, is the most common secondary cause of hypertension. Primary aldosteronism is associated with an increased risk of cardiovascular disease and kidney dysfunction compared to essential hypertension. Excess aldosterone can lead to harmful metabolic and other pathophysiological alterations, as well as cause inflammatory, oxidative, and fibrotic effects in the heart, kidney, and blood vessels. These alterations can result in coronary artery disease, including ischemia and myocardial infarction, left ventricular hypertrophy, heart failure, arterial fibrillation, intracarotid intima thickening, cerebrovascular disease, and chronic kidney disease. Thus, aldosterone affects several tissues, especially in the cardiovascular system, and the metabolic and pathophysiological alterations are related to severe diseases. Therefore, understanding the effects of aldosterone on the body is important for health maintenance in hypertensive patients. In this review, we focus on currently available evidence regarding the role of aldosterone in alterations of the cardiovascular and renal systems. We also describe the risk of cardiovascular events and renal dysfunction in hyperaldosteronism.
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New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy.
Int J Mol Sci2023 Mar;24(6):. doi: 5089.
Gallo Giovanna, Lanza Oreste, Savoia Carmine,
Abstract
Cardiorenal syndrome consists in the coexistence of acute or chronic dysfunction of heart and kidneys resulting in a cascade of feedback mechanisms and causing damage to both organs associated with high morbidity and mortality. In the last few years, different biomarkers have been investigated with the aim to achieve an early and accurate diagnosis of cardiorenal syndrome, to provide a prognostic role and to guide the development of targeted pharmacological and non-pharmacological therapies. In such a context, sodium-glucose cotransporter 2 (SGLT2) inhibitors, recommended as the first-line choice in the management of heart failure, might represent a promising strategy in the management of cardiorenal syndrome due to their efficacy in reducing both cardiac and renal outcomes. In this review, we will discuss the current knowledge on the pathophysiology of cardiorenal syndrome in adults, as well as the utility of biomarkers in cardiac and kidney dysfunction and potential insights into novel therapeutics.
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Sestrin2 Mediates Metformin Rescued the Age-Related Cardiac Dysfunctions of Cardiorenal Syndrome Type 3.
Cells2023 Mar;12(6):. doi: 845.
Iglesias Migdalia, Wang Hao, Krause-Hauch Meredith, Ren Di, Zoungrana Linda Ines, Li Zehui, Zhang Jie, Wei Jin, Yadav Nikita, Patel Kshama, Fatmi Mohammad Kasim, Liu Ruisheng, Lesnefsky Edward J, Li Ji,
Abstract
Acute kidney injury (AKI) leads to acute cardiac injury and dysfunction in cardiorenal syndrome Type 3 (CRS3) through oxidative stress (OS). The stress-inducible Sestrin2 (Sesn2) protein reduces reactive oxygen species (ROS) accumulation and activates AMP-dependent protein kinase (AMPK) to regulate cellular metabolism and energetics during OS. Sesn2 levels and its protective effects decline in the aged heart. Antidiabetic drug metformin upregulates Sesn2 levels in response to ischemia-reperfusion (IR) stress. However, the role of metformin in CRS3 remains unknown. This study seeks to explore how the age-related decrease in cardiac Sesn2 levels contributes to cardiac intolerance to AKI-induced insults, and how metformin ameliorates CRS3 through Sesn2. Young (3-5 months) and aged (21-23 months) C57BL/6J wild-type mice along with cardiomyocyte-specific knockout (cSesn2) and their wild type of littermate (Sesn2) C57BL/6J mice were subjected to AKI for 15 min followed by 24 h of reperfusion. Cardiac and mitochondrial functions were evaluated through echocardiograms and seahorse mitochondria respirational analysis. Renal and cardiac tissue was collected for histological analysis and immunoblotting. The results indicate that metformin could significantly rescue AKI-induced cardiac dysfunction and injury Sesn2 through an improvement in systolic and diastolic function, fibrotic and cellular damage, and mitochondrial function in young, Sesn2, and especially aged mice. Metformin significantly increased Sesn2 expression under AKI stress in the aged left-ventricular tissue. Thus, this study suggests that Sesn2 mediates the cardioprotective effects of metformin during post-AKI.
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Blunted humoral immune response to the fourth dose of BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis.
Clin Exp Nephrol2023 Mar;():. doi: 10.1007/s10157-023-02342-0.
Kanai Daisuke, Wakui Hiromichi, Hanaoka Masaaki, Haze Tatsuya, Azushima Kengo, Shinoda Satoru, Tsukamoto Shunichiro, Taguchi Shinya, Kinguchi Sho, Kanaoka Tomohiko, Toya Yoshiyuki, Hirawa Nobuhito, Kato Hideaki, Watanabe Fumimasa, Hanaoka Kanako, Mitsuhashi Hiroshi, Yamaguchi Satoshi, Ohnishi Toshimasa, Tamura Kouichi,
Abstract
BACKGROUND:
We aimed to investigate the impact of a fourth dose of BNT162b2 vaccine (Comirnaty®, Pfizer-BioNTech) on anti-SARS-CoV-2 (anti-S IgG) antibody titers in patients receiving hemodialysis (HD) and healthcare workers (HCWs).
METHODS:
A multi-institutional retrospective study at five dialysis clinics in Japan was conducted using 238 HD patients and 58 HCW controls who received four doses of the BNT162b2 mRNA vaccine. Anti-S IgG titers were measured at 1, 3, and 6 months after the second dose, at 1 and 5/6 months after the third dose, and at 1 month after the fourth dose of vaccine.
RESULTS:
The log anti-S IgG titers of the HD patients after the second vaccination were significantly lower than those of the control group, but equalized 1 month after the third vaccination: 9.94 (95% CI 9.82-10.10) vs. 9.81 (95% CI 9.66-9.96), (P?=?0.32). In both groups, the fold-increase in anti-S IgG titers was significantly lower after the fourth dose than after the third dose of vaccine. In addition, there was a strong negative correlation between antibody titers 1 month after the fourth vaccination and antibody titers immediately before the vaccination. In both groups, the waning rate of anti-S IgG titers from the post-vaccination peak level after the third vaccine dose was significantly slower than that after the second dose.
CONCLUSIONS:
These findings suggest that the humoral immune response was blunted after the fourth dose of the conventional BNT162b2 vaccine. However, multiple vaccinations could extend the window of humoral immune protection.
© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.
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Artificial Diuresis: animal studies on efficacy and safety of a new miniaturized device for extracorporeal ultrafiltration.
Cardiorenal Med2023 Mar;():. doi: 10.1159/000530382.
Lorenzin Anna, Sgarabotto Luca, Bacci Maria Laura, Elmi Alberto, Ventrella Domenico, Aniballi Camilla, Zanella Monica, Brendolan Alessandra, Di Lullo Luca, Ronco Claudio,
Abstract
INTRODUCTION:
We have recently developed a new miniaturized device for extracorporeal ultrafiltration to be used in patients with fluid overload: Artificial Diuresis-1, or AD1 (Medica S.p.A., Medolla, Italy). The device has a reduced priming volume and operates at very low pressure and flow regimes and is designed to perform extracorporeal UF at bedside. After accurate experiments carried out in vitro, we report in this paper the results of in vivo tests ultrafiltration session carried out in selected animals according to veterinary best practice.
MATERIALS AND METHODS:
The AD1 kit is pre-filled with sterile isotonic solution and operates with a polysulfone mini-filter MediSulfone (Polysulfone at 50000 Dalton). A collection bag with a volumetric scale is connected to the UF line and the ultrafiltrate is obtained by gravity based on the height at which the ultrafiltrate collection bag is placed. Animals were prepared and anesthetized. Jugular vein was cannulated with a double lumen catheter. Three six hours sessions of ultrafiltration were scheduled with a target fluid removal of 1500 ml. Heparin was used as anticoagulant.
RESULTS:
In all treatments the target value of ultrafiltration was obtained in the absence of major clinical or technical problems with a maximum deviation from the scheduled ultrafiltration rate lower than 10%. The device resulted safe, reliable, accurate and easily usable thanks to a user friendly interface and the very small dimensions.
CONCLUSIONS:
This study opens the way for clinical trials in different settings including departments with low intensity of care and even in ambulatory centers or patient's home.
The Author(s). Published by S. Karger AG, Basel.
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Joint Modeling of Clinical and Biomarker Data in Acute Kidney Injury Defines Unique Subphenotypes with Differing Outcomes: The ASSESS-AKI Study.
Clin J Am Soc Nephrol2023 Mar;():. doi: 10.2215/CJN.0000000000000156.
Vasquez-Rios George, Oh Wonsuk, Lee Samuel, Bhatraju Pavan, Mansour Sherry G, Moledina Dennis G, Gulamali Faris F, Siew Edward D, Garg Amit X, Sarder Pinaki, Chinchilli Vernon M, Kaufman James S, Hsu Chi-Yuan, Liu Kathleen D, Kimmel Paul L, Go Alan S, Wurfel Mark M, Himmelfarb Jonathan, Parikh Chirag R, Coca Steven G, Nadkarni Girish N,
Abstract
BACKGROUND:
Acute kidney injury (AKI) is a heterogeneous syndrome. Current subphenotyping approaches have only used limited laboratory data to understand a much more complex condition.
METHODS:
We focused on AKI patients from the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI). We utilized hierarchical clustering with Ward's linkage on biomarkers of inflammation, injury, and repair/health. We then evaluated clinical differences between subphenotypes and examined their associations with cardiorenal events and death using Cox proportional hazard models.
RESULTS:
We included 748 patients with AKI, 543 (72.6%) of them had AKI stage 1, 112 (15.0%) had AKI stage 2, and 93 (12.4%) had AKI stage 3. The mean age (± SD) was 64 (13) years, 508 (67.9%) were men, and the median follow-up was 4.7 years (Q1: 2.9, Q3: 5.7). Patients with AKI subphenotype 1 (N=181) had the highest KIM-1 and troponin T levels. Subphenotype 2 (N=250) had the highest levels of UMOD. AKI subphenotype 3 (N=159) was comprised of patients with markedly high pro-BNP, TNFR1, and TNFR2 and low concentrations of KIM-1 and NGAL. Finally, patients with subphenotype 4 (N=158) predominantly had sepsis-AKI and the highest levels of vascular/kidney inflammation (YKL-40, MCP-1) and injury (NGAL, KIM-1). AKI subphenotypes 3 and 4 were independently associated with a higher risk of death compared to subphenotype 2; adjusted hazard ratios (aHR) of 2.9 (95% CI: 1.8 - 4.6) and 1.6 (1.01 - 2.6, p=0.04), respectively. Subphenotype 3 was also independently associated with a 3-fold risk of chronic kidney disease and cardiovascular events.
CONCLUSIONS:
We discovered four AKI subphenotypes with differing clinical features, biomarker profiles, that are associated with longitudinal clinical outcomes.
Copyright © 2023 by the American Society of Nephrology.
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Urea reduction in acute kidney injury and mortality risk.
Kidney Blood Press Res2023 Mar;():. doi: 10.1159/000530237.
Chávez-Íñiguez Jonathan S, Maggiani-Aguilera Pablo, González-Barajas David, Rizo-Topete Lilia, Galindo Pablo, Rifkin Brian, Chávez-Alonso Gael, Martínez-Aguilar Alma I, Pérez-Hernández Sandra Cristina, Hernández-Morales Karla, Camacho-Guerrero Jahir R, Pérez-Venegas Miguel A, Oseguera-González Alexa N, Murguia-Soto Cesar, Navarro-Blackaller Guillermo, Medina-González Ramón, Alcantar-Vallin Maria de la Luz, Renoirte-López Karina, García-García Guillermo,
Abstract
Introduction Urea is a toxin present in acute kidney injury (AKI). We hypothesize that reduction in serum urea levels might improve clinical outcomes. We examined the association between the reduction in urea and mortality. Methods Patients with AKI admitted to the Hospital Civil de Guadalajara were enrolled in this retrospective cohort study. We create 4 groups of urea reduction (UXR) stratified by their decrease in urea from the highest index value in comparison to the value on day 10 (0%, 1-25%, 26-50% and >50%), or at the time of death or discharge if prior to 10 days. Our primary endpoint was to observe the association between UXR and mortality. Secondary observations included determination of which types of patients achieved a UXR >50%, whether the modality of kidney replacement therapy (KRT) effected changes in UXR, and if serum creatinine (sCr) value changes were similarly associated with patient mortality. Results A total of 651 AKI patients were enrolled. The mean age was 54.1 years, and 58.6% were male. AKI 3 was present in 58.5%, the mean admission urea was 154 mg/dL. KRT was started in 32.4%, and 18.9% died. A trend toward decreased risk of death was observed in association with the magnitude of UXR. The best survival (94.3%) was observed in patients with a UXR >50%, and the highest mortality (72.1%) was observed in patients achieving a UXR of 0%. After adjusting for age, sex, diabetes mellitus, CKD, antibiotics, sepsis, hypovolemia, cardio-renal syndrome, shock and AKI stage the 10-day mortality was higher in groups that did not achieve a UXR of at least 25% (OR 1.20). Patients achieving a UXR >50% were most likely initiated on dialysis due to a diagnosis of the uremic syndrome, or had a diagnosis of obstructive nephropathy. Percentage change in sCr was also associated with increased mortality risk. Conclusions In our retrospective cohort of AKI patients, the percent decrease in UXR from admission was associated with a stratified risk of death. Patients with a UXR >25% had the best associated outcomes. Overall, a greater magnitude in UXR was associated with improved patient survival.
The Author(s). Published by S. Karger AG, Basel.
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In vivo evaluation of the effect of sickle cell hemoglobin S, C and therapeutic transfusion on erythrocyte metabolism and cardiorenal dysfunction.
Am J Hematol2023 Mar;():. doi: 10.1002/ajh.26923.
D'Alessandro Angelo, Nouraie S Mehdi, Zhang Yingze, Cendali Francesca, Gamboni Fabia, Reisz Julie A, Zhang Xu, Bartsch Kyle W, Galbraith Matthew D, Gordeuk Victor R, Gladwin Mark T,
Abstract
Despite a wealth of exploratory plasma metabolomics studies in sickle cell disease (SCD), no study to date has evaluate a large and well phenotyped cohort to compare the primary erythrocyte metabolome of hemoglobin SS, SC and transfused AA red blood cells (RBCs) in vivo. The current study evaluates the RBC metabolome of 587 subjects with sickle cell sickle cell disease (SCD) from the WALK-PHaSST clinical cohort. The set includes hemoglobin SS, hemoglobin SC SCD patients, with variable levels of HbA related to RBC transfusion events. Here we explore the modulating effects of genotype, age, sex, severity of hemolysis, and transfusion therapy on sickle RBC metabolism. Results show that RBCs from patients with Hb SS genotypes - compared to AA RBCs from recent transfusion events or SC RBCs - are characterized by significant alterations of RBC acylcarnitines, pyruvate, sphingosine 1-phosphate, creatinine, kynurenine and urate metabolism. Surprisingly, the RBC metabolism of SC RBCs is dramatically different from SS, with all glycolytic intermediates significantly elevated in SS RBCs, with the exception of pyruvate. This result suggests a metabolic blockade at the ATP-generating phosphoenolpyruvate to pyruvate step of glycolysis, which is catalyzed by redox-sensitive pyruvate kinase. Metabolomics, clinical and hematological data were collated in a novel online portal. In conclusion, we identified metabolic signatures of HbS RBCs that correlate with the degree of steady state hemolytic anemia, cardiovascular and renal dysfunction and mortality. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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A case of successful catheter ablation for biatrial reentrant tachycardia after a Mustard operation for dextro-transposition of the great arteries.
HeartRhythm Case Rep2023 Mar;9(3):140-143. doi: 10.1016/j.hrcr.2022.11.014.
Taguchi Yuka, Matsumoto Katsumi, Shoda Morio, Nitta Manabu, Hosoda Junya, Ishikawa Toshiyuki,
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High Intensity Interval Training Versus Moderate Continuous Training in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis.
Curr Probl Cardiol2023 Mar;():101720. doi: 10.1016/j.cpcardiol.2023.101720.
Siddiqi Tariq Jamal, Rashid Ahmed Mustafa, Javaid Syed Sarmad, Siddiqi Ahmed Kamal, Usman Muhammad Shariq, Hervir Oliver, Kamimura Daisuke, Lavie Carl J, Mentz Robert J, Butler Javed, Hall Michael E,
Abstract
BACKGROUND:
High-intensity interval training (HIIT) is a novel training approach that improves cardiopulmonary fitness and functional capacity in numerous chronic conditions, however its impact in patients with heart failure (HF) with preserved ejection fraction (HFpEF) is uncertain. We evaluated data from prior studies reporting the effects of HIIT versus moderate continuous training (MCT), on cardiopulmonary exercise outcomes in patients with HFpEF.
METHODS:
PubMed and SCOPUS were queried from inception till February 1, 2022 for all randomized controlled trials (RCT) comparing the effect of HIIT versus MCT in patients with HFpEF on peak oxygen consumption (peak VO), left atrial volume index (LAVI), respiratory exchange ratio (RER), and ventilatory efficiency (VE/CO slope). A random-effects model was applied, and the weighted mean difference (WMD) of each outcome was reported with 95% confidence intervals (CI).
RESULTS:
Three RCTs (total N=150 patients with HFpEF), with a follow-up of 4 - 52 weeks were included in our analysis. Our pooled analysis demonstrated that HIIT significantly improved peak VO (WMD?=?1.46 mL .kg .min (0.88, 2.05); p
CONCLUSION:
Across current RCT data, HIIT, compared to MCT, had a significant impact on improving peak VO. Conversely, there was no significant change in LAVI, RER, and VE/CO2 slope between HFpEF patients undertaking HIIT as opposed to MCT.
Copyright © 2023. Published by Elsevier Inc.
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Prognosis of Patients with Acute Kidney Injury due to Type 1 Cardiorenal Syndrome Receiving Continuous Renal Replacement Therapy.
Cardiorenal Med2023 Mar;():0. doi: 10.1159/000527111.
Watanabe Yusuke, Inoue Tsutomu, Nakano Shintaro, Okada Hirokazu,
Abstract
Introduction The prognosis of patients with acute kidney injury (AKI) caused by type 1 cardiorenal syndrome (CRS) requiring continuous renal replacement therapy (CRRT) is unclear. We investigated the in-hospital mortality and prognostic factors in these patients. Methods We retrospectively identified 154 consecutive adult patients who received CRRT for AKI caused by type 1 CRS between January 1, 2013, and December 31, 2019. We excluded patients who underwent cardiovascular surgery and those with chronic kidney disease stage 5. The primary outcome was in-hospital mortality. Cox proportional hazards analysis was performed to analyze independent predictors of in-hospital mortality. Results The median age of patients at admission was 74.0 years (interquartile range: 63.0-80.0); 70.8% were male. The in-hospital mortality rate was 68.2%. Age ?80 years (hazard ratio, 1.87; 95% confidence interval [CI], 1.21-2.87; P=0.004); previous hospitalization for acute heart failure (hazard ratio, 1.67; 95% CI, 1.13-2.46; P=0.01), vasopressor or inotrope use (hazard ratio, 5.88; 95% CI, 1.43 - 24.1; P=0.014), and mechanical ventilation (hazard ratio, 2.24; 95% CI, 1.46 -3.45; P
The Author(s). Published by S. Karger AG, Basel.
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Role of Sodium-Glucose Cotransporter 2 inhibitors for management of diabetes mellitus in renal transplant recipients; and management strategies for post-transplant hypertension.
Am J Nephrol2023 Mar;():. doi: 10.1159/000530296.
Singh Amit Pal, Kalil Roberto, Weir Matthew R,
Abstract
Background Diabetes mellitus and hypertension are the leading causes of cardiovascular disease in renal transplant recipients. This review looks at the potential role of sodium-glucose co-transporter 2 inhibitors (SGLT2is) and reviews the management strategies for hypertension in this population. Summary Large-scale clinical trials are needed to study the potential cardiorenal benefits and risks of complications in renal transplant recipients. Future clinical trials are also needed to define optimal blood pressure treatment goals and therapies and how they influence graft and patient survival. Key Messages Multiple recent prospective randomized clinical trials have shown the benefits of using SGLT2is to improve cardiorenal outcomes in patients with chronic kidney disease with or without diabetes mellitus. Renal transplant recipients were not included in these trials due to concerns about genitourinary complications. Hence the role of these agents in this population is unclear. A number of small studies have highlighted the safety of using these agents in renal transplant recipients. Post-transplant hypertension is a complex problem requiring individualized management. Recent guidelines recommend using a calcium channel blocker or angiotensin receptor blocker as the first-line anti-hypertensive agents in adult renal transplant recipients.
S. Karger AG, Basel.
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Intrarenal Doppler ultrasonography in patients with HFrEF and acute decompensated heart failure undergoing recompensation.
Clin Res Cardiol2023 Mar;():. doi: 10.1007/s00392-023-02184-6.
Wallbach M, Valentova M, Schroeter M R, Alkabariti A, Iraki I, Leha A, Tampe D, Hasenfuß G, Zeisberg M, Hellenkamp K, Koziolek M J,
Abstract
OBJECTIVES:
Renal venous congestion due to backward heart failure leads to disturbance of renal function in acute decompensated heart failure (ADHF). Whether decongestion strategies have an impact on renal venous congestion is unknown. Objective was to evaluate changes in intrarenal hemodynamics using intrarenal Doppler ultrasonography (IRD) in patients with heart failure with reduced ejection fraction (HFrEF) and ADHF undergoing recompensation.
METHODS:
Prospective observational study in patients with left ventricular ejection fraction (LV-EF)???35% hospitalized due to ADHF. IRD measurement was performed within the first 48 h of hospitalisation and before discharge. Decongestion strategies were based on clinical judgement according to heart failure guidelines. IRD was used to assess intrarenal venous flow (IRVF) pattern, venous impedance index (VII) and resistance index (RI). Laboratory analyses included plasma creatinine, eGFR and albuminuria.
RESULTS:
A number of 35 patients with ADHF and LV-EF???35% were included into the study. IRD could be performed in 30 patients at inclusion and discharge. At discharge, there was a significant reduction of VII from a median of 1.0 (0.86-1.0) to 0.59 (0.26-1.0) (p?0.01) as well as improvement of IRVF pattern categories (p?0.05) compared to inclusion. Albuminuria was significantly reduced from a median of 78 mg/g creatinine (39-238) to 29 mg/g creatinine (16-127) (p?=?0.02) and proportion of patients with normoalbuminuria increased (p?=?0.01). Plasma creatinine and RI remained unchanged (p?=?0.73; p?=?0.43).
DISCUSSION:
This is the first study showing an effect of standard ADHF therapy on parameters of renal venous congestion in patients with HFrEF and ADHF. Doppler sonographic evaluation of renal venous congestion might provide additional information to guide decongestion strategies in patients with ADHF.
© 2023. The Author(s).
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Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2.
Hum Exp Toxicol2023 ;42():9603271231165678. doi: 10.1177/09603271231165678.
Wang Jianjie, Zou Jianqin, Zhao Cheng, Yu Han, Teng Jiajia, Dong Lei,
Abstract
BACKGROUND:
Syringaresinol processes anti-inflammatory and antioxidative activity. However, the effects of syringaresinol on cardiorenal fibrosis caused by cardiorenal syndrome type 2 (CRS2) are unclear.
METHODS:
Molecular docking predicted binding activity of syringaresinol to heat shock protein 90 (HSP90). The toxicity of a 4-weeks treatment with 20 mg/kg of syringaresinol was observed by measuring serum pro-inflammatory cytokines levels and by cardiorenal pathology. A CRS2 rad model was established by myocardial infarction using ligation over an 8 week-period. Rats were divided into five groups, including sham, CRS2, pimitespib, syringaresinol, and HSP90 + syringaresinol. Rats were received a 4-weeks daily treatment with 10 mg/kg pimitespib (a HSP90 inhibitor) or 20 mg/kg syringaresinol. Recombinant adeno-associated virus (rAAV) carrying a periostin (PE) promoter driving the expression of wild-type HSP90 (rAAV9-PE-HSP90, 1 × 10 ?g) was treated intravenously once in CRS2 model rats. Cardiorenal function and pathology were assessed. Expressions of HSP90 and TGF-?1 in the myocardium and kidney were measured by immunohistochemistry and western blotting.
RESULTS:
Syringaresinol showed good binding activity with HSP90, and no signs of toxicity in rats following treatment. Pimitespib or syringaresinol significantly improved the cardiorenal function and fibrosis in rats with CRS2. Meanwhile, the rAAV9-PE-HSP90 injection obviously blocked the effects of syringaresinol.
CONCLUSIONS:
Syringaresinol targets HSP90 to suppress CRS2-induced cardiorenal fibrosis, providing a promising therapeutic drug for CRS2.
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Effect of Urinary Albumin Creatinine Ratio on Cardiovascular Morbidity and Mortality in Diabetes Patients with Atherosclerotic Disease.
Diabetes Metab Syndr Obes2023 ;16():819-828. doi: 10.2147/DMSO.S400970.
Gao Fei, Zhou Yang, Yan Xiaoming, Huang Haozhang, Liang Guoxiao, Xie Yongyi, Zhu Qijiong, Chen Ziming, Wang Bo, Li Huanqiang, Mai Ziling, Ying Ming, Liu Jin, Chen Shiqun, Chen Jiyan,
Abstract
BACKGROUND:
Diabetes mellitus (DM) patients with increased urinary albumin creatinine ratio (uACR) have higher risk of mortality, while it is unclear in DM patients with atherosclerotic cardiovascular disease (ASCVD).
METHODS:
We analysed 2832 DM patients with ASCVD in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Patients were divided into 3 groups according to their uACR level (normal group: uACR
RESULTS:
During a median follow-up of 2.1 years, among 2832 patients (mean age: 63.3 ± 9.9 years, 29.1% women), 434 patients (15.3%) had moderately increased uACR, and 203 patients (7.2%) had severely increased uACR. Compared to patients in normal group, patients had higher cardiovascular mortality in moderately increased group and severely increased group (2.5% vs 9.9% vs 16.7%, P
CONCLUSION:
In our study, we found nearly a quarter of DM patients with ASCVD had increased uACR, and they have over 2- or 3-fold risk of cardiovascular mortality than those with normal uACR. UACR is a helpful indicator for risk stratification and treatment target for DM patients with ASCVD.
© 2023 Gao et al.
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