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Li J, Sun Y, Ren J, Wu Y, He Z. Machine Learning for In-hospital Mortality Prediction in Critically Ill Patients With Acute Heart Failure: A Retrospective Analysis Based on the MIMIC-IV Database. J Cardiothorac Vasc Anesth 2025; 39:666-674. [PMID: 39779429 DOI: 10.1053/j.jvca.2024.12.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/03/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND The incidence, mortality, and readmission rates for acute heart failure (AHF) are high, and the in-hospital mortality for AHF patients in the intensive care unit (ICU) is higher. However, there is currently no method to accurately predict the mortality of AHF patients. METHODS The Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database was used to perform a retrospective study. Patients meeting the inclusion criteria were identified from the MIMIC-Ⅳ database and randomly divided into a training set (n = 3,580, 70%) and a validation set (n = 1,534, 30%). The variates collected include demographic data, vital signs, comorbidities, laboratory test results, and treatment information within 24 hours of ICU admission. By using the least absolute shrinkage and selection operator (LASSO) regression model in the training set, variates that affect the in-hospital mortality of AHF patients were screened. Subsequently, in the training set, five common machine learning (ML) algorithms were applied to construct models using variates selected by LASSO to predict the in-hospital mortality of AHF patients. The predictive ability of the models was evaluated for sensitivity, specificity, accuracy, the area under the curve of receiver operating characteristics, and clinical net benefit in the validation set. To obtain a model with the best predictive ability, the predictive ability of common scoring systems was compared with the best ML model. RESULTS Among the 5,114 patients, in-hospital mortality was 12.5%. Comparing the area under the curve, the XGBoost model had the best predictive ability among all ML models, and the XGBoost model was chosen as the final model for its higher net benefit. Its predictive ability was superior to common scoring systems. CONCLUSIONS The XGBoost model can effectively predict the in-hospital mortality of AHF patients admitted to the ICU, which may assist clinicians in precise management and early intervention for patients with AHF to reduce mortality.
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Affiliation(s)
- Jun Li
- Department of Anesthesiology, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Yiwu Sun
- Department of Anesthesiology, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Jie Ren
- Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
| | - Yifan Wu
- Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai, China
| | - Zhaoyi He
- Surgical Anesthesia Center, The First People's Hospital of Longquanyi District, Chengdu, China.
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Rinaldi PM, Rihl MF, Boniatti MM. VExUS Score at Discharge as a Predictor of Readmission in Patients with Acute Decompensated Heart Failure: A Cohort Study. Arq Bras Cardiol 2024; 121:e20230745. [PMID: 38896589 PMCID: PMC11164437 DOI: 10.36660/abc.20230745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/16/2024] [Accepted: 02/15/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND Residual venous congestion is a major contributor to readmission of patients with heart failure, and the venous excess ultrasound (VExUS) score is a potentially useful tool to evaluate systemic congestion. OBJECTIVES To investigate the association between VExUS score before hospital discharge among patients with heart failure and the risk of readmission due to acute decompensated heart failure (ADHF) within 90 days after discharge. METHODS This prospective cohort study enrolled adults with signs and symptoms of ADHF, left ventricular ejection fraction of 40% or below (heart failure with reduced ejection fraction), New York Heart Association functional class II to IV symptoms, and clinical evidence of venous congestion necessitating intravenous diuretics. Just prior to discharge, we conducted VExUS score evaluation. The primary outcome was a composite endpoint of readmission or emergency visits due to ADHF within 90 days following hospital discharge. Statistical significance was set at p < 0.05. RESULTS The cohort comprised 49 individuals, 11 (22.4%) of whom experienced the primary outcome. At discharge, 34.7% of participants had VExUS score 2 or 3. Patients with VExUS 2 and 3 had a higher proportion of the primary outcome when compared with patients with VExUS of 0 (35.3% versus 9%, p = 0.044). CONCLUSIONS A significant proportion of patients with heart failure with reduced ejection fraction admitted for ADHF presented clinical and ultrasound signs of residual congestion at discharge. Patients with VExUS score of 2 or 3 at the time of hospital discharge were found to be at higher risk of readmissions or emergency visits due to ADHF after 90 days.
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Affiliation(s)
- Paulo Maciel Rinaldi
- Universidade Federal do Rio Grande do SulPorto AlegreRSBrasilUniversidade Federal do Rio Grande do Sul, Porto Alegre, RS – Brasil
- Faculdade de MedicinaUNISINOSSão LeopoldoRSBrasilFaculdade de Medicina da Universidade do Vale do Rio dos Sinos (UNISINOS), São Leopoldo, RS – Brasil
| | - Marcos Frata Rihl
- Universidade Federal do Rio Grande do SulPorto AlegreRSBrasilUniversidade Federal do Rio Grande do Sul, Porto Alegre, RS – Brasil
- Hospital de Clínicas de Porto AlegrePorto AlegreRSBrasilHospital de Clínicas de Porto Alegre, Porto Alegre, RS – Brasil
| | - Márcio Manozzo Boniatti
- Universidade Federal do Rio Grande do SulPorto AlegreRSBrasilUniversidade Federal do Rio Grande do Sul, Porto Alegre, RS – Brasil
- Hospital de Clínicas de Porto AlegrePorto AlegreRSBrasilHospital de Clínicas de Porto Alegre, Porto Alegre, RS – Brasil
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Alfieri M, Bruscoli F, Di Vito L, Di Giusto F, Scalone G, Marchese P, Delfino D, Silenzi S, Martoni M, Guerra F, Grossi P. Novel Medical Treatments and Devices for the Management of Heart Failure with Reduced Ejection Fraction. J Cardiovasc Dev Dis 2024; 11:125. [PMID: 38667743 PMCID: PMC11050600 DOI: 10.3390/jcdd11040125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/13/2024] [Accepted: 04/18/2024] [Indexed: 04/28/2024] Open
Abstract
Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of "heart failure with reduced ejection fraction" (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.
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Affiliation(s)
- Michele Alfieri
- Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital “Umberto I-Lancisi-Salesi”, 60121 Ancona, Italy; (M.A.); (F.G.)
| | - Filippo Bruscoli
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Luca Di Vito
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Federico Di Giusto
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Giancarla Scalone
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Procolo Marchese
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Domenico Delfino
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Simona Silenzi
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
| | - Milena Martoni
- Medical School, Università degli Studi “G. d’Annunzio”, 66100 Chieti, Italy;
| | - Federico Guerra
- Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital “Umberto I-Lancisi-Salesi”, 60121 Ancona, Italy; (M.A.); (F.G.)
| | - Pierfrancesco Grossi
- Cardiology Unit, C. and G. Mazzoni Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy; (F.B.); (F.D.G.); (G.S.); (P.M.); (D.D.); (S.S.); (P.G.)
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Crespo-Aznarez S, Campos-Saenz de Santamaría A, Sánchez-Marteles M, Josa-Laorden C, Ruiz-Laiglesia F, Amores-Arriaga B, Garcés-Horna V, Tejel-Puisac R, Julián-Ansón MA, Giménez-López I, Pérez-Calvo JI, Rubio-Gracia J. Prognostic Impact of Induced Natriuresis in Acute Decompensated Heart Failure and Its Association with Intraabdominal Pressure and Other Congestion Markers: A Multimodal Approach to Congestion Assessment. J Clin Med 2024; 13:1053. [PMID: 38398366 PMCID: PMC10888634 DOI: 10.3390/jcm13041053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 02/08/2024] [Accepted: 02/10/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Congestion is an essential issue in patients with heart failure (HF). Standard treatments do not usually achieve decongestion, and various strategies have been proposed to guide treatment, such as determination of natriuresis. After starting treatment with loop diuretics, we postulate that initial natriuresis might help treatment titration, decongestion, and improve prognosis. METHODS It was a prospective and observational study. Patients admitted with the diagnosis of HF decompensation were eligible. An assessment of congestion was performed during the first 48 h. RESULTS A total of 113 patients were included. A poor diuretic response was observed in 39.8%. After the first 48 h, patients with a greater diuretic response on admission (NaU > 80 mmol/L) showed fewer pulmonary b lines (12 vs. 15; p = 0.084), a lower IVC diameter (18 mm vs. 22 mm; p = 0.009), and lower IAP figures (11 mmHg vs. 13 mmHg; p = 0.041). Survival analysis tests demonstrated significant differences showing a higher proportion of all-cause mortality (ACM) and HF rehospitalization in the poor-diuretic-response group (log-rank test = 0.020). CONCLUSIONS Up to 40% of the patients presented a poorer diuretic response at baseline, translating into worse outcomes. Patients with an optimal diuretic response showed significantly higher abdominal decongestion at 48 h and a better prognosis regarding ACM and/or HF rehospitalizations.
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Affiliation(s)
- Silvia Crespo-Aznarez
- Internal Medicine Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (S.C.-A.); (A.C.-S.d.S.); (M.S.-M.); (F.R.-L.); (V.G.-H.)
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
| | - Amelia Campos-Saenz de Santamaría
- Internal Medicine Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (S.C.-A.); (A.C.-S.d.S.); (M.S.-M.); (F.R.-L.); (V.G.-H.)
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
| | - Marta Sánchez-Marteles
- Internal Medicine Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (S.C.-A.); (A.C.-S.d.S.); (M.S.-M.); (F.R.-L.); (V.G.-H.)
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
| | - Claudia Josa-Laorden
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
- Internal Medicine Department, Hospital Royo Villanova, 50015 Zaragoza, Spain
| | - Fernando Ruiz-Laiglesia
- Internal Medicine Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (S.C.-A.); (A.C.-S.d.S.); (M.S.-M.); (F.R.-L.); (V.G.-H.)
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
| | - Beatriz Amores-Arriaga
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
- Emergency Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain
| | - Vanesa Garcés-Horna
- Internal Medicine Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (S.C.-A.); (A.C.-S.d.S.); (M.S.-M.); (F.R.-L.); (V.G.-H.)
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
| | - Ruben Tejel-Puisac
- Clinical Biochemistry Deparment, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (R.T.-P.); (M.A.J.-A.)
| | - María Angel Julián-Ansón
- Clinical Biochemistry Deparment, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (R.T.-P.); (M.A.J.-A.)
| | - Ignacio Giménez-López
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
- Aragon’s Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Juan Ignacio Pérez-Calvo
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Jorge Rubio-Gracia
- Internal Medicine Department, Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain; (S.C.-A.); (A.C.-S.d.S.); (M.S.-M.); (F.R.-L.); (V.G.-H.)
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain; (C.J.-L.); (B.A.-A.); (I.G.-L.); (J.I.P.-C.)
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
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Cosentino N, Marenzi G, Muratori M, Magrì D, Cattadori G, Agostoni P. Fluid balance in heart failure. Eur J Prev Cardiol 2023; 30:ii9-ii15. [PMID: 37819223 DOI: 10.1093/eurjpc/zwad166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 05/10/2023] [Accepted: 05/12/2023] [Indexed: 10/13/2023]
Abstract
Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a critical therapeutic target in this clinical setting. The first therapeutic strategy in HF patients with fluid overload is optimization of diuretic intervention to maximize water and sodium excretion. When diuretic therapy fails to relieve congestion, renal replacement therapy represents the only alternative option for fluid removal, as well as a way to restore diuretic responsiveness. On this background, the pathophysiology of fluid balance in HF is complex, with heart, kidney, and lung being deeply involved in volume regulation and management. Therefore, the interplay between these organs should be appreciated and considered when fluid overload in HF patients is targeted.
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Affiliation(s)
- Nicola Cosentino
- Centro Cardiologico Monzino, I.R.C.C.S., Via Parea 4, Milan 20138, Italy
- Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
| | - Giancarlo Marenzi
- Centro Cardiologico Monzino, I.R.C.C.S., Via Parea 4, Milan 20138, Italy
| | - Manuela Muratori
- Centro Cardiologico Monzino, I.R.C.C.S., Via Parea 4, Milan 20138, Italy
| | - Damiano Magrì
- Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant'Andrea, 'Sapienza' Università degli Studi di Roma, Roma 00198, Italy
| | - Gaia Cattadori
- Unità Operativa Cardiologia Riabilitativa, IRCCS Multimedica, Milan 20123, Italy
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Bisht H, Tripathi A, Arya A, Konat A, Patel D, Godhani D, Kamaria R, Shah P, Chudasama G, Jain P, Sharma K. Ultrafiltration in Heart Failure: A Review. Cureus 2023; 15:e39933. [PMID: 37409214 PMCID: PMC10318566 DOI: 10.7759/cureus.39933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2023] [Indexed: 07/07/2023] Open
Abstract
Ultrafiltration is an effective method to get rid of fluid retention and congestion in patients with acute decompensated heart failure (HF) without affecting the circulating volume. Although its efficacy in comparison to diuretics is debatable, the evaluation of our analysis is based on various studies that comprise published clinical trials on ultrafiltration and studies comparing the efficacy of diuretics and ultrafiltration. Apart from this, we also look at literature that provides shortcomings of the said procedure and its scope for future advancements. Heart failure ultimately leads to volume overload, which is a highly concerning complication. Diuretics have been used as a first-line treatment for fluid overload but are becoming inefficacious due to the development of resistance and renal dysfunction. Ultrafiltration, on the other hand, is an attractive alternative to counter volume overload and congestion, which are unresponsive to medical therapy. There is also evidence that it significantly decreases the probability of future episodes of decompensation. There are, however, disagreements about whether ultrafiltration is an effective method to improve mortality in these patients. There is a lack of conclusive studies demonstrating the superiority of one fluid removal method over another. Hence, it is imperative to continue searching for the most effective method to treat congestion. Priority should be given to more mechanistic studies regarding ultrafiltration.
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Affiliation(s)
- Himanshi Bisht
- Medicine, Byramjee Jeejeebhoy (BJ) Medical College, Ahmedabad, IND
| | - Apoorva Tripathi
- Medicine, Byramjee Jeejeebhoy (BJ) Medical College, Ahmedabad, IND
| | - Akshat Arya
- Internal Medicine, Byramjee Jeejeebhoy (BJ) Medical College, Ahmedabad, IND
| | - Ashwati Konat
- Department of Zoology, Biomedical Technology and Human Genetics, Gujarat University, Ahmedabad, IND
| | - Divya Patel
- Internal Medicine, Byramjee Jeejeebhoy (BJ) Medical College, Ahmedabad, IND
| | - Dhruvin Godhani
- Internal Medicine, Gujarat Medical Education and Research Society (GMERS) Medical College, Gandhinagar, IND
| | - Rushi Kamaria
- Internal Medicine, Government Medical College, Surat, IND
| | - Parita Shah
- Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Gayatri Chudasama
- Internal Medicine, Byramjee Jeejeebhoy (BJ) Medical College, Ahmedabad, IND
| | - Pragya Jain
- Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Kamal Sharma
- Cardiology, Dr. Kamal Sharma Cardiology Clinic, Ahmedabad, IND
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Haran C, Sivakumaran Y. Contemporary uses of inferior vena cava balloon occlusion. Ann Vasc Surg 2023:S0890-5096(23)00238-8. [PMID: 37121341 DOI: 10.1016/j.avsg.2023.04.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 05/02/2023]
Abstract
The evolution of the hybrid operative environment has expanded the utility of inferior vena cava balloon occlusion (IVCBO) in contemporary surgical practice. First described in the management of acute decompensated heart failure and venous thromboembolism, IVCBO has been utilised in deployment of thoracic endoprosthesis, repair of aorto-caval fistula, management of inferior vena cava (IVC) tumour thrombus and abdominal IVC trauma. More recently, IVCBO has also been utilised as a therapeutic strategy to assist patients with reduced ejection fraction and exercise tolerance in the form of an implantable device. Here we present a narrative review of the physiological impact of IVCBO as well as its historical, contemporary and future uses. The contemporary utilisation of IVCBO is a novel example of employing endovascular technology in the hybrid operative environment; paramount for the modern vascular surgeon who is now increasingly involved in multi-disciplinary management of complex clinical presentations.
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Affiliation(s)
- Cheyaanthan Haran
- Department of Vascular Surgery, Auckland City Hospital, Auckland, New Zealand; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
| | - Yogeesan Sivakumaran
- Department of Vascular Surgery, Princess Alexandra Hospital, Brisbane, Australia; Greater Brisbane Clinical School, University of Queensland, Brisbane, Australia
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8
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Slow Continuous Ultrafiltration in Regional Citrate Anticoagulation Performed with a Standard Fluid Infusion Central Venous Catheter in Intensive Care Unit for Fluid Overload in Acute on Chronic Heart Failure: A Case Report. J Clin Med 2023; 12:jcm12030988. [PMID: 36769636 PMCID: PMC9917685 DOI: 10.3390/jcm12030988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/15/2023] [Accepted: 01/21/2023] [Indexed: 02/01/2023] Open
Abstract
Slow continuous ultrafiltration (SCUF) is an extracorporeal therapy able to reduce fluid overload in chronic or acute heart failure resistant to diuretics. An in-vitro study demonstrated the SCUF feasibility using a standard fluid infusion central venous catheter (CVC). We describe the clinical application of this SCUF in regional citrate anticoagulation (SCUF-RCA) in a patient admitted to the Intensive Care Unit for acute decompensate heart failure with severe systemic fluid overload resistant to diuretics. To avoid risks deriving from a new catheterization, we used a pre-existing multi-lumen CVC for drug administration to provide 10 h of SCUF-RCA with a blood flow of 35 mL/min and 100 mL/h of ultrafiltration with a final weight loss of 1 Kilogram without technical and clinical complications. The patient had a hemodynamics improvement with the diuresis recovery from the previous oliguria after the SCUF-RCA. This clinical case can open the use of the SCUF-RCA in the clinical practice to treat the fluid overload unresponsive to maximal diuretic therapy not exposing the patient to the risks and complications related to the use of SCUF with CVC for dialysis and systemic anticoagulation with heparin. Accordingly, this technique may be useful in the treatment of fluid overload in outpatients.
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9
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Oyama MA, Adin D. Toward quantification of loop diuretic responsiveness for congestive heart failure. J Vet Intern Med 2022; 37:12-21. [PMID: 36408832 PMCID: PMC9889629 DOI: 10.1111/jvim.16590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 11/11/2022] [Indexed: 11/22/2022] Open
Abstract
Diuretics, such as furosemide, are routinely administered to dogs with congestive heart failure (CHF). Traditionally, dose and determination of efficacy primarily are based on clinical signs rather than quantitative measures of drug action. Treatment of human CHF patients increasingly is guided by quantification of urine sodium concentration (uNa) and urine volume after diuretic administration. Use of these and other measures of diuretic responsiveness is associated with decreased duration of hospitalization, complication rates, future rehospitalization, and mortality. At their core, loop diuretics act through natriuresis, and attention to body sodium (Na) stores and handling offers insight into the pathophysiology of CHF and pharmacology of diuretics beyond what is achievable from clinical signs alone. Human patients with low diuretic responsiveness or diuretic resistance are at risk for difficult or incomplete decongestion that requires diuretic intensification or other remedial strategies. Identification of the specific etiology of resistance in a patient can help tailor personalized interventions. In this review, we advance the concept of loop diuretic responsiveness by highlighting Na and natriuresis. Specifically, we review body water homeostasis and congestion in light of the increasingly recognized role of interstitial Na, propose definitions for diuretic responsiveness and resistance in veterinary subjects, review relevant findings of recent studies, explain how the particular cause of resistance can guide treatment, and identify current knowledge gaps. We believe that a quantitative approach to loop diuretic usage primarily involving natriuresis will advance our understanding and care of dogs with CHF.
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Affiliation(s)
- Mark A. Oyama
- Clinical Sciences and Advanced MedicineUniversity of Pennsylvania, MJR‐VHUP‐CardiologyPhiladelphiaPennsylvaniaUSA
| | - Darcy Adin
- Large Animal Clinical SciencesUniversity of FloridaGainesvilleFloridaUSA
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Abassi Z, Khoury EE, Karram T, Aronson D. Edema formation in congestive heart failure and the underlying mechanisms. Front Cardiovasc Med 2022; 9:933215. [PMID: 36237903 PMCID: PMC9553007 DOI: 10.3389/fcvm.2022.933215] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/05/2022] [Indexed: 11/13/2022] Open
Abstract
Congestive heart failure (HF) is a complex disease state characterized by impaired ventricular function and insufficient peripheral blood supply. The resultant reduced blood flow characterizing HF promotes activation of neurohormonal systems which leads to fluid retention, often exhibited as pulmonary congestion, peripheral edema, dyspnea, and fatigue. Despite intensive research, the exact mechanisms underlying edema formation in HF are poorly characterized. However, the unique relationship between the heart and the kidneys plays a central role in this phenomenon. Specifically, the interplay between the heart and the kidneys in HF involves multiple interdependent mechanisms, including hemodynamic alterations resulting in insufficient peripheral and renal perfusion which can lead to renal tubule hypoxia. Furthermore, HF is characterized by activation of neurohormonal factors including renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), endothelin-1 (ET-1), and anti-diuretic hormone (ADH) due to reduced cardiac output (CO) and renal perfusion. Persistent activation of these systems results in deleterious effects on both the kidneys and the heart, including sodium and water retention, vasoconstriction, increased central venous pressure (CVP), which is associated with renal venous hypertension/congestion along with increased intra-abdominal pressure (IAP). The latter was shown to reduce renal blood flow (RBF), leading to a decline in the glomerular filtration rate (GFR). Besides the activation of the above-mentioned vasoconstrictor/anti-natriuretic neurohormonal systems, HF is associated with exceptionally elevated levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). However, the supremacy of the deleterious neurohormonal systems over the beneficial natriuretic peptides (NP) in HF is evident by persistent sodium and water retention and cardiac remodeling. Many mechanisms have been suggested to explain this phenomenon which seems to be multifactorial and play a major role in the development of renal hyporesponsiveness to NPs and cardiac remodeling. This review focuses on the mechanisms underlying the development of edema in HF with reduced ejection fraction and refers to the therapeutic maneuvers applied today to overcome abnormal salt/water balance characterizing HF.
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Affiliation(s)
- Zaid Abassi
- Department of Physiology, Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
- Department of Laboratory Medicine, Rambam Health Care Campus, Haifa, Israel
- *Correspondence: Zaid Abassi,
| | - Emad E. Khoury
- Department of Physiology, Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
| | - Tony Karram
- Department of Vascular Surgery and Kidney Transplantation, Rambam Health Care Campus, Haifa, Israel
| | - Doron Aronson
- Department of Cardiology, Rambam Health Care Campus, Haifa, Israel
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11
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Kanwar MK, Everett KD, Gulati G, Brener MI, Kapur NK. Epidemiology and management of right ventricular-predominant heart failure and shock in the cardiac intensive care unit. EUROPEAN HEART JOURNAL. ACUTE CARDIOVASCULAR CARE 2022; 11:584-594. [PMID: 35767583 DOI: 10.1093/ehjacc/zuac063] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 06/15/2023]
Abstract
Cardiogenic shock from left ventricular failure is a common presentation in the intensive care unit. In contrast, right ventricular (RV)-predominant heart failure (HF) causing shock is less well recognized. We review the epidemiology and mechanisms of RV-predominant HF and discuss pharmacologic and device-based approaches for the management of this challenging clinical problem.
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Affiliation(s)
- Manreet K Kanwar
- Department of Medicine, Cardiovascular Institute at Allegheny Health Network, Pittsburgh, PA, USA
| | - Kay D Everett
- Department of Medicine, The CardioVascular Center, Tufts Medical Center, 800 Washington Street, Box # 80, Boston, MA 02111, USA
| | - Gaurav Gulati
- Department of Medicine, The CardioVascular Center, Tufts Medical Center, 800 Washington Street, Box # 80, Boston, MA 02111, USA
| | - Michael I Brener
- Department of Medicine, Columbia University Medical Center, New York, NY, USA
| | - Navin K Kapur
- Department of Medicine, The CardioVascular Center, Tufts Medical Center, 800 Washington Street, Box # 80, Boston, MA 02111, USA
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12
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Booth LC, de Silva RAU, Pontes RB, Yao ST, Hood SG, Lankadeva YR, Kosaka J, Eikelis N, Lambert GW, Schlaich MP, May CN. Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure. Hypertension 2021; 78:706-715. [PMID: 34333989 DOI: 10.1161/hypertensionaha.120.16054] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Lindsea C Booth
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia
| | - R Anethra U de Silva
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia
| | - Roberto B Pontes
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia.,Department of Physiology, Cardiovascular Division, Federal University of São Paulo, Brazil (R.B.P.)
| | - Song T Yao
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia.,Department of Anatomy and Physiology, MDHS (S.T.Y.), University of Melbourne, Parkville, Victoria, Australia
| | - Sally G Hood
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia
| | - Yugeesh R Lankadeva
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia
| | - Junko Kosaka
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia.,Department of Anesthesiology and Resuscitology, Okayama University Hospital, Japan (J.K.)
| | - Nina Eikelis
- Iverson Health Innovation Research Institute and School of Health Sciences, Swinburne University of Technology, Hawthorn, Victoria, Australia (N.E., G.W.L.)
| | - Gavin W Lambert
- Iverson Health Innovation Research Institute and School of Health Sciences, Swinburne University of Technology, Hawthorn, Victoria, Australia (N.E., G.W.L.)
| | - Markus P Schlaich
- Dobney Hypertension Centre, School of Medicine-Royal Perth Hospital Unit, University of Western Australia, Perth (M.P.S.)
| | - Clive N May
- Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia
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13
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Delgado J, Ansorena D, Van Hecke T, Astiasarán I, De Smet S, Estévez M. Meat lipids, NaCl and carnitine: Do they unveil the conundrum of the association between red and processed meat intake and cardiovascular diseases?_Invited Review. Meat Sci 2021; 171:108278. [DOI: 10.1016/j.meatsci.2020.108278] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 08/07/2020] [Accepted: 08/07/2020] [Indexed: 12/15/2022]
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Loughran KA, Larouche-Lebel É, Huh T, Testani JM, Rao VS, Oyama MA. Prediction and measurement of diuretic responsiveness after oral administration of furosemide to healthy dogs and dogs with congestive heart failure. J Vet Intern Med 2020; 34:2253-2264. [PMID: 33125814 PMCID: PMC7694836 DOI: 10.1111/jvim.15952] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 10/13/2020] [Accepted: 10/19/2020] [Indexed: 02/06/2023] Open
Abstract
Background In human patients, cumulative urine volume (uVol) and urine sodium (uNa) can be predicted using spot urine samples and these quantitative measures help detect low diuretic responsiveness (LDR). Hypothesis/objectives Formulas using spot urine samples predict cumulative uVol and uNa output after oral administration of furosemide to dogs. Animals Eight healthy dogs, 6 dogs with congestive heart failure (CHF). Methods Prospective interventional study. Spot urine samples at 180 and 270 minutes after furosemide (3 mg/kg PO) were used to predict cumulative uVol and uNa output over 7 hours. Differentiation of dogs fulfilling predefined criteria for LDR was examined using receiver operating characteristic (ROC) curves. Results Predicted uNa output at 180 minutes (rs = 0.763, [95% confidence interval [CI], 0.375‐0.923], P = .002) and 270 minutes (r = 0.816, [95% CI, 0.503‐0.940], P < .001) was highly correlated to 7‐hour uNa output. Predicted uVol at 180 minutes (r = 0.598, [95% CI, 0.098‐0.857], P = .02) and 270 minutes (r = 0.791, [95% CI, 0.450‐0.931], P < .001) was moderately correlated to 7‐hour uVol. Predicted uNa using 180‐minute (area under the curve [AUC], 0.933 [95% CI, 0.804‐1.000]) and 270‐minute (AUC, 0.911 [95% CI, 0.756‐1.000]) samples identified dogs with LDR (n = 5) with high accuracy. Conclusions and Clinical Importance Urinary Na excretion and uVol are complementary but distinct aspects of diuretic responsiveness in dogs. Quantification of diuretic responsiveness in the clinical setting opens new diagnostic, treatment, and monitoring strategies.
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Affiliation(s)
- Kerry A Loughran
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Éva Larouche-Lebel
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Terry Huh
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jeffrey M Testani
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Veena S Rao
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Mark A Oyama
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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15
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Bouabdallaoui N, Beaubien-Souligny W, Oussaïd E, Henri C, Racine N, Denault AY, Rouleau JL. Assessing Splanchnic Compartment Using Portal Venous Doppler and Impact of Adding It to the EVEREST Score for Risk Assessment in Heart Failure. CJC Open 2020; 2:311-320. [PMID: 32995715 PMCID: PMC7499287 DOI: 10.1016/j.cjco.2020.03.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 03/21/2020] [Indexed: 12/20/2022] Open
Abstract
Background The Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) score has proven useful for risk prediction in acute decompensated heart failure (ADHF). However, this score does not include the characterization of the splanchnic compartment, which has been involved in worsening heart failure. Refining this score by integrating an assessment of the splanchnic compartment would allow for a better risk assessment. Therefore, we aimed to characterize the patterns of portal vein pulsatility (PVP), an ultrasound metric used for the assessment of splanchnic compartment and their determinants in patients with ADHF, to explore the relationships between abnormal patterns of PVP and outcomes, and to evaluate the added value of PVP to the EVEREST score for risk assessment in ADHF. Methods Portal vein flow was assessed prospectively on admission and at discharge in 95 patients with ADHF using pulsed-wave Doppler. Abnormal PVP was defined for values ≥ 50%. Cox proportional hazards models were used for the assessment of the relationship between PVP and outcomes. Results Overall, 64% of patients on admission and 24% at discharge had abnormal PVP. PVP on admission was inversely correlated with right ventricular function (tricuspid annular plane systolic excursion, ρ = −0.434) and pulmonary pressure (ρ = 0.346), P < 0.05. Although PVP was associated with all-cause mortality (hazard ratio, 1.028, P < 0.001), the addition of this metric to the EVEREST score had little effect on its C-index (0.813 vs 0.818) for risk assessment. Conclusions Abnormal PVP is frequent and associated with right ventricular dysfunction in ADHF. Although abnormal PVP identifies higher-risk patients, this metric does not improve the performance of the EVEREST score for risk assessment.
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Affiliation(s)
- Nadia Bouabdallaoui
- Department of Medicine of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
| | - William Beaubien-Souligny
- Anesthesia and Critical Care Division of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
| | - Essaïd Oussaïd
- Pharmacogenomic Center of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
| | - Christine Henri
- Department of Medicine of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
| | - Normand Racine
- Department of Medicine of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
| | - André Y Denault
- Anesthesia and Critical Care Division of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
| | - Jean L Rouleau
- Department of Medicine of the Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada
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Othman KMS, Mostafa MAR, Yosef AE, Abdeltawab AA. Safety and efficacy of off-label use of ivabradine in patients with acute heart failure. J Saudi Heart Assoc 2019; 31:179-187. [PMID: 31333320 PMCID: PMC6614597 DOI: 10.1016/j.jsha.2019.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/22/2019] [Accepted: 05/24/2019] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Ivabradine is approved to improve exercise tolerance and quality of life in patients with chronic heart failure; its use in acute heart failure (AHF) has not previously been studied. METHODS Forty adult patients admitted with AHF were randomized into two groups; Group 1 patients were prescribed beta-blockers (BBs) and Group 2 patients were prescribed ivabradine. Both groups were given optimum anti-failure treatment for AHF. All patients were assessed for heart rate (HR), 6-minute walk test (6MWT), New York Heart Association (NYHA) classification, and Minnesota Living With Heart Failure Questionnaire (MLWHFQ) before and after 1 month of therapy. RESULTS BBs or ivabradine among optimum medical therapy for AHF resulted in a significant improvement in all the studied parameters (NYHA class; 6MWT distance; HR and Borg scale dyspnea/fatigue score before and after the walk). The MLWHFQ was significantly worse during the follow-up in both groups. At the end of follow-up, there was a comparable beneficial effect attributed to the significant HR reduction observed in both groups. CONCLUSION The results of this pilot study demonstrated the safety of the early use of ivabradine alone versus BBs when tolerated in patients admitted with AHF (both acutely decompensated as well as de novo). Both groups achieved comparable reduction in HR with improvement in functional capacity and exercise tolerance.
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Affiliation(s)
- Khaled M. Said Othman
- Department of Cardiology, Faculty of Medicine, Ain Shams University, Cairo EgyptEgypt
| | | | - Ahmed Elsayed Yosef
- Department of Cardiology, Faculty of Medicine, Ain Shams University, Cairo EgyptEgypt
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17
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Nijst P, Olinevich M, Hilkens P, Martens P, Dupont M, Tang WHW, Lambrichts I, Noben JP, Mullens W. Dermal Interstitial Alterations in Patients With Heart Failure and Reduced Ejection Fraction: A Potential Contributor to Fluid Accumulation? Circ Heart Fail 2019; 11:e004763. [PMID: 30002114 DOI: 10.1161/circheartfailure.117.004763] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 06/18/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Large networks of interstitial glycosaminoglycans help to regulate water and electrolyte homeostasis. The relation between dermal interstitial alterations and occurrence of edema in heart failure patients with reduced ejection fraction (HFrEF) is unknown. We hypothesize that in HFrEF patients (1) interstitial glycosaminoglycan density is increased, (2) changes in the interstitial glycosaminoglycan network are associated with interstitial fluid accumulation, and (3) there is a link between the interstitial glycosaminoglycan network and the renin-angiotensin-aldosterone system. METHODS AND RESULTS Two punch biopsies of the skin were obtained in healthy subjects (n=18) and HFrEF patients (n=29). Alcian blue staining and immunostaining for the angiotensin II type 1 receptor was performed. After obtaining tissue water content, total interstitial glycosaminoglycan (uronic acid) and sulfated glycosaminoglycan were quantified. A venous blood sample, clinical examination, and echocardiography were obtained. A significantly higher interstitial glycosaminoglycan content was observed in HFrEF patients compared with healthy subjects (uronic acid: 13.0±4.2 versus 9.6±1.6 μg/mg; P=0.002; sulfated glycosaminoglycan: 14.1 [11.7; 18.1] versus 10.0 [9.1; 10.8] μg/mg; P<0.001). Uronic acid and sulfated glycosaminoglycan density were strongly associated with tissue water content and peripheral edema (uronic acid: ρ=0.66; P<0.0001 and sulfated glycosaminoglycan: τ=0.58; P<0.0001). Expression of the angiotensin II type 1 receptor was found on dermal cells, although use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker was associated with significantly lower levels of interstitial glycosaminoglycans in HFrEF patients. CONCLUSIONS Interstitial glycosaminoglycan concentration is significantly increased in HFrEF patients compared with healthy subjects and correlated with tissue water content and clinical signs of volume overload. A better appreciation of the interstitial compartment might improve management of volume overload in HF.
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Affiliation(s)
- Petra Nijst
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (P.N., P.M., M.D., W.M.)
- Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (P.N., P.H., P.M.)
| | - Mikhail Olinevich
- Biomedical Research Institute and Transnational University Limburg, School of Life Sciences, Hasselt University, Belgium (P.H., I.L., J.-P.N., W.M., M.O.)
| | - Petra Hilkens
- Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (P.N., P.H., P.M.)
- Biomedical Research Institute and Transnational University Limburg, School of Life Sciences, Hasselt University, Belgium (P.H., I.L., J.-P.N., W.M., M.O.)
| | - Pieter Martens
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (P.N., P.M., M.D., W.M.)
- Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (P.N., P.H., P.M.)
| | - Matthias Dupont
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (P.N., P.M., M.D., W.M.)
| | - W H Wilson Tang
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (W.H.W.T.)
| | - Ivo Lambrichts
- Biomedical Research Institute and Transnational University Limburg, School of Life Sciences, Hasselt University, Belgium (P.H., I.L., J.-P.N., W.M., M.O.)
| | - Jean-Paul Noben
- Biomedical Research Institute and Transnational University Limburg, School of Life Sciences, Hasselt University, Belgium (P.H., I.L., J.-P.N., W.M., M.O.)
| | - Wilfried Mullens
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (P.N., P.M., M.D., W.M.).
- Biomedical Research Institute and Transnational University Limburg, School of Life Sciences, Hasselt University, Belgium (P.H., I.L., J.-P.N., W.M., M.O.)
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Untreated Relative Hypotension Measured as Perfusion Pressure Deficit During Management of Shock and New-Onset Acute Kidney Injury-A Literature Review. Shock 2019; 49:497-507. [PMID: 29040214 DOI: 10.1097/shk.0000000000001033] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Maintaining an optimal blood pressure (BP) during shock is a fundamental tenet of critical care. Optimal BP targets may be different for different patients. In current practice, too often, uniform BP targets are pursued which may result in inadvertently accepting a degree of untreated relative hypotension, i.e., the deficit between patients' usual premorbid basal BP and the achieved BP, during vasopressor support. Relative hypotension is a common but an under-recognized and an under-treated sign among patients with potential shock state. From a physiological perspective, any relative reduction in the net perfusion pressure across an organ (e.g., renal) vasculature has a potential to overwhelm autoregulatory mechanisms, which are already under stress during shock. Such perfusion pressure deficit may consequently impact organs' ability to function or recover from an injured state. This review discusses such pathophysiologic mechanisms in detail with a particular focus on the risk of new-onset acute kidney injury (AKI). To review current literature, databases of Medline, Embase, and Google scholar were searched to retrieve articles that either adjusted BP targets based on patients' premorbid BP levels or considered relative hypotension as an exposure endpoint and assessed its association with clinical outcomes among acutely ill patients. There were no randomized controlled trials. Only seven studies could be identified and these were reviewed in detail. These studies indicated a significant association between the degree of relative hypotension that was inadvertently accepted in real-world practice and new-onset organ dysfunction or subsequent AKI. However, this is not a high-quality evidence. Therefore, well-designed randomized controlled trials are needed to evaluate whether adoption of individualized BP targets, which are initially guided by patient's premorbid basal BP and then tailored according to clinical response, is superior to conventional BP targets for vasopressor therapy, particularly among patients with vasodilatory shock states.
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Abstract
BACKGROUND Any treatment decision should be tailored to the individual patients' characteristics. A personalized approach aims to help better selecting the patients who are likely to benefit most from a treatment decision. In the systolic blood pressure intervention trial, intensive treatment reduced the rate of major cardiovascular events, but increased the rate of serious adverse events (SAEs). OBJECTIVES To assess the trade-off between efficacy and safety to simultaneously quantify an individual patient's absolute benefit and absolute harm, helping clinicians making better therapeutic choices in daily practice. METHODS Multivariable Poisson regression models were used to identify independent risk factors for: primary composite cardiovascular outcome and major SAEs = safety. Estimates from the models were used to quantify each individual risk. RESULTS Subclinical cardiovascular disease, number of antihypertensive agents, current smoking, age, urine albumin-to-creatinine ratio, and serum creatinine were associated with increased risk of both primary outcome events and SAEs. Triglycerides were associated with increased primary outcome events only, and chronic kidney disease and female sex with SAEs only. The models were well calibrated and showed good performance (c-index for safety = 0.69 and c-index for efficacy = 0.72). For the primary outcome, there is a steep gradient in risk by fifths of the predicted model and a similar gradient exists for the safety outcome predicted model. Mortality within 1 year of an efficacy outcome (as assessed by the Kaplan-Meier method) was nearly three-fold higher than following a safety outcome (21.9 vs. 7.5%). If one judges the clinical importance of efficacy and safety outcomes based on their 1-year mortality, then there is a net benefit of intensive therapy for almost all patients. CONCLUSION Antihypertensive treatment intensification is associated with lower cardiovascular event rates; however, it increases the risk of adverse events. However, having adverse events has less weight when it comes to therapeutic decisions and antihypertensive therapy intensification is beneficial for the great majority of patients included in the systolic blood pressure intervention trial.
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Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hülsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2018; 20:1505-1535. [DOI: 10.1002/ejhf.1236] [Citation(s) in RCA: 373] [Impact Index Per Article: 53.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 05/17/2018] [Accepted: 05/21/2018] [Indexed: 12/28/2022] Open
Affiliation(s)
- Maria G. Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC); Instituto de Investigación Biomédica de A Coruña (INIBIC), CIBERCV, UDC; La Coruña Spain
| | - Marco Metra
- Cardiology; University of Brescia; Brescia Italy
| | - Lars H. Lund
- Department of Medicine, Unit of Cardiology; Karolinska Institute; Stockholm Sweden
| | - Davor Milicic
- Department for Cardiovascular Diseases; University Hospital Center Zagreb, University of Zagreb; Zagreb Croatia
| | | | | | - Finn Gustafsson
- Department of Cardiology; Rigshospitalet; Copenhagen Denmark
| | - Steven Tsui
- Transplant Unit; Royal Papworth Hospital; Cambridge UK
| | - Eduardo Barge-Caballero
- Complexo Hospitalario Universitario A Coruña (CHUAC); Instituto de Investigación Biomédica de A Coruña (INIBIC), CIBERCV, UDC; La Coruña Spain
| | - Nicolaas De Jonge
- Department of Cardiology; University Medical Center Utrecht; Utrecht The Netherlands
| | - Maria Frigerio
- Transplant Center and De Gasperis Cardio Center; Niguarda Hospital; Milan Italy
| | - Righab Hamdan
- Department of Cardiology; Beirut Cardiac Institute; Beirut Lebanon
| | - Tal Hasin
- Jesselson Integrated Heart Center; Shaare Zedek Medical Center; Jerusalem Israel
| | - Martin Hülsmann
- Department of Internal Medicine II; Medical University of Vienna; Vienna Austria
| | | | - Luciano Potena
- Heart and Lung Transplant Program; Bologna University Hospital; Bologna Italy
| | - Johann Bauersachs
- Department of Cardiology and Angiology; Medical School Hannover; Hannover Germany
| | - Aggeliki Gkouziouta
- Heart Failure and Transplant Unit; Onassis Cardiac Surgery Centre; Athens Greece
| | - Arjang Ruhparwar
- Department of Cardiac Surgery; University of Heidelberg; Heidelberg Germany
| | - Arsen D. Ristic
- Department of Cardiology of the Clinical Center of Serbia; Belgrade University School of Medicine; Belgrade Serbia
| | | | | | - Petar Seferovic
- Department of Internal Medicine; Belgrade University School of Medicine and Heart Failure Center, Belgrade University Medical Center; Belgrade Serbia
| | - Frank Ruschitzka
- University Heart Center; University Hospital Zurich; Zurich Switzerland
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Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure: Current Status and Prospects for Further Research. J Am Coll Cardiol 2017; 69:2428-2445. [PMID: 28494980 PMCID: PMC5632523 DOI: 10.1016/j.jacc.2017.03.528] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 03/07/2017] [Indexed: 01/18/2023]
Abstract
More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients’ vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration.
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Mullens W, Verbrugge FH, Nijst P, Tang WHW. Renal sodium avidity in heart failure: from pathophysiology to treatment strategies. Eur Heart J 2017; 38:1872-1882. [DOI: 10.1093/eurheartj/ehx035] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 01/16/2017] [Indexed: 01/10/2023] Open
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Arrigo M, Parissis JT, Akiyama E, Mebazaa A. Understanding acute heart failure: pathophysiology and diagnosis. Eur Heart J Suppl 2016. [DOI: 10.1093/eurheartj/suw044] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Nakagawa A, Atsukawa M, Tsubota A, Kondo C, Okubo T, Arai T, Itokawa N, Narahara Y, Iwakiri K. Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients. World J Gastroenterol 2016; 22:5104-5113. [PMID: 27275103 PMCID: PMC4886386 DOI: 10.3748/wjg.v22.i21.5104] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 03/19/2016] [Accepted: 03/30/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.
METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.
RESULTS: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10-6) and -1.3 kg (P = 1.83 × 10-5), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10-4). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors.
CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.
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Nijst P, Verbrugge FH, Grieten L, Dupont M, Steels P, Tang WHW, Mullens W. The pathophysiological role of interstitial sodium in heart failure. J Am Coll Cardiol 2015; 65:378-388. [PMID: 25634838 DOI: 10.1016/j.jacc.2014.11.025] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 11/19/2014] [Accepted: 11/20/2014] [Indexed: 01/05/2023]
Abstract
The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptoms. Most HF hospitalizations are related to sodium (Na(+)) and fluid retention resulting from neurohumoral up-regulation. Recent insights suggest that Na(+) is not distributed in the body solely as a free cation, but that it is also bound to large interstitial glycosaminoglycan (GAG) networks in different tissues, which have an important regulatory function. In HF, high Na(+) intake and neurohumoral alterations disrupt GAG structure, leading to loss of the interstitial buffer capacity and disproportionate interstitial fluid accumulation. Moreover, a diminished endothelial GAG network (the endothelial glycocalyx) results in increased vascular resistance and disturbed endothelial nitric oxide production. New imaging modalities can help evaluate interstitial Na(+) and endothelial glycocalyx integrity. Furthermore, several therapies have been proven to stabilize interstitial GAG networks. Hence, a better appreciation of this new Na(+) "compartment" might improve current management of HF.
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Affiliation(s)
- Petra Nijst
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Frederik H Verbrugge
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Lars Grieten
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Matthias Dupont
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Paul Steels
- Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - W H Wilson Tang
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Wilfried Mullens
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
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Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan. J Gastroenterol 2015; 50:1047-53. [PMID: 25689936 PMCID: PMC4592499 DOI: 10.1007/s00535-015-1052-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 02/03/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients with hypoalbuminemia often fail to respond to increased doses of loop diuretics. We therefore performed a post hoc analysis to investigate the pharmacological action of tolvaptan and whether it is dependent on the serum albumin level. METHODS This analysis was based on four previous clinical trials of tolvaptan in patients with liver cirrhosis who exhibited insufficient response to conventional diuretics. We analyzed the correlation between the change in the initial 24-h cumulative urine volume from baseline and the serum albumin level at baseline, and assessed potential predictive factors of response to tolvaptan. RESULTS The correlation coefficient was 0.029 in the placebo group and -0.112 in the 7.5 mg tolvaptan group of patients with liver cirrhosis. Administration of tolvaptan provoked a stable response regardless of the serum albumin level. Tolvaptan use was identified as a significant predictor of pharmacological action, and was shown to change the initial urine volume by 885 mL (P < 0.0001) in liver cirrhosis patients. CONCLUSIONS In this post hoc analysis, tolvaptan increased the initial urine volume from baseline regardless of serum albumin levels. Use of tolvaptan as an add-on therapy to loop diuretics can be considered an optimal therapeutic option in patients with insufficient response to loop diuretics.
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Kwong JS, Yu CM. Ultrafiltration for acute decompensated heart failure: A systematic review and meta-analysis of randomized controlled trials. Int J Cardiol 2014; 172:395-402. [DOI: 10.1016/j.ijcard.2014.01.069] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 01/13/2014] [Accepted: 01/18/2014] [Indexed: 12/22/2022]
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Triposkiadis F, Starling RC, Boudoulas H, Giamouzis G, Butler J. The cardiorenal syndrome in heart failure: cardiac? renal? syndrome? Heart Fail Rev 2013; 17:355-66. [PMID: 22086438 DOI: 10.1007/s10741-011-9291-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
There has been increasing interest on the so-called cardiorenal syndrome (CRS), defined as a complex pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. In this review, we contend that there is lack of evidence warranting the adoption of a specific clinical construct such as the CRS within the heart failure (HF) syndrome by demonstrating that: (a) the approaches and tools regarding the definition of kidney involvement in HF are suboptimal; (b) development of renal failure in HF is often confounded by age, hypertension, and diabetes; (c) worsening of renal function (WRF) in HF may be largely independent of alterations in cardiac function; (d) the bidirectional association between HF and renal failure is not unique and represents one of the several such associations encountered in HF; and (e) inflammation is a common denominator for HF and associated noncardiac morbidities. Based on these arguments, we believe that dissecting one of the multiple bidirectional associations in HF and constructing the so-called cardiorenal syndrome is not justified pathophysiologically. Fully understanding of all morbid associations and not only the cardiorenal is of great significance for the clinician who is caring for the patient with HF.
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Abstract
Heart failure and kidney disease often coexist, and each of the two conditions may lead to progression of the other. Kidney dysfunction is an independent prognostic factor in patients with either acute or chronic heart failure. Worsening renal function may be related with poorer outcomes as well. Multiple mechanisms are involved in the cardio-renal interaction, including hemodynamic abnormalities, neurohormonal and inflammatory activation, oxidative stress, anemia, and abnormalities in mineral and vitamin D metabolism. Serum creatinine has limitations for the assessment of kidney function in patients with heart failure as its short-term changes are dependent on hemodynamic changes and fluid status. New biomarkers of glomerular and tubular function might allow an earlier and more accurate detection of worsening renal function.
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Affiliation(s)
- Marco Metra
- Institute of Cardiology, University of Brescia, Brescia, Italy.
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Wańkowicz Z, Próchnicka A, Olszowska A, Baczyński D, Krzesiński P, Dziuk M. Extracorporeal versus peritoneal ultrafiltration in diuretic-resistant congestive heart failure--a review. Med Sci Monit 2012; 17:RA271-81. [PMID: 22129914 PMCID: PMC3628132 DOI: 10.12659/msm.882118] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Diuretic-resistant congestive heart failure in the form of type 2 cardiorenal syndrome is a problem of growing significance in everyday clinical practice because of high morbidity and mortality. There has been scant progress in the treatment of overhydration, the main cause of symptoms in this group of patients. The aim of our review is to present recent advances in the ultrafiltration therapy of congestive heart failure, with special attention to the new dedicated device for extracorporeal isolated ultrafiltration, as well as modifications of peritoneal dialysis in the form of peritoneal ultrafiltration with icodextrin solution and incremental peritoneal dialysis. Technical and clinical features, costs and potential risks of available devices for isolated ultrafiltration are presented. This method should be reserved for patients with true diuretic resistance as part of a more complex strategy aiming at the adequate control of fluid retention. Peritoneal ultrafiltration is presented as a viable alternative to extracorporeal ultrafiltration because of medical and psychosocial benefits of home-based therapy, lower costs and more effective daily ultrafiltration. In conclusion, large, properly randomized and controlled clinical trials with long-term follow-up will be essential in assessing the logistics and cost-effectiveness of both methods. Most importantly, however, they should be able to evaluate the impact of both methods on preservation of renal function and delaying the progression of heart failure by interrupting the vicious circle of cardiorenal syndrome. Our review is supplemented with the case report of the use of peritoneal ultrafiltration with a single 12-hour nighttime icodextrin exchange as a life-saving procedure in a patient with congestive heart failure resistant to pharmacological treatment.<br />
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Affiliation(s)
- Zofia Wańkowicz
- Department of Internal Diseases, Nephrology and Dialysis, Military Medicine Institute, Central Hospital, Ministry of National Defence, Warsaw, Poland.
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