|
1
|
Berezin AE, Berezina TA, Novikov EV, Berezin OO. Low levels of adropin are associated with acute kidney injury after decongestion in patients with acutely decompensated heart failure. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY PLUS 2025; 12:100302. [DOI: 10.1016/j.jmccpl.2025.100302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2025]
|
|
2
|
Marchetta M, Parato AG, Vizzari G, Chiricolo G, Massaro G, Russo G, Sasso S, Carciotto G, Carerj S, Di Bella G, Natale A, Sangiorgi GM, Micari A. Effects of early initiation of mineralocorticoid receptor antagonist therapy in acute decompensated heart failure: a systematic review and meta-analysis. J Cardiol 2025:S0914-5087(25)00129-7. [PMID: 40412617 DOI: 10.1016/j.jjcc.2025.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 05/10/2025] [Accepted: 05/16/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND Acute heart failure (AHF) is a major cause of hospitalization, with high morbidity and mortality. Mineralocorticoid receptor antagonists (MRAs) improve outcomes in chronic heart failure, but their role and optimal timing in AHF remain unclear. Early initiation may enhance hemodynamic stability, yet concerns about hyperkalemia and renal dysfunction limit their use. This meta-analysis evaluates the efficacy and safety of early MRA initiation in AHF. METHODS A systematic search of PubMed, SCOPUS, and Cochrane databases identified studies comparing early in-hospital MRA therapy plus standard care versus standard care alone in AHF patients. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated using a random-effects model. Primary outcomes included cardiovascular and all-cause mortality, heart failure rehospitalizations, and safety outcomes (hyperkalemia, renal deterioration, hypotension, and hypokalemia). RESULTS Six studies (N = 11,039) were included. Early MRA initiation reduced cardiovascular mortality (OR 0.73, 95 % CI 0.59-0.92; p = 0.007), heart failure rehospitalizations (OR 0.56, 95 % CI 0.40-0.78; p = 0.0008), and renal deterioration (OR 0.78, 95 % CI 0.66-0.92; p = 0.003). No significant effect on all-cause mortality was observed (OR 0.88, 95 % CI 0.62-1.24; p = 0.46). A non-significant trend toward increased hyperkalemia emerged (OR 1.45, 95 % CI 0.57-3.68; p = 0.43). CONCLUSION This meta-analysis suggests that early MRA initiation in AHF improves cardiovascular outcomes and reduces rehospitalizations with an acceptable safety profile. Further large-scale randomized controlled studies are needed to confirm its long-term clinical impact.
Collapse
Affiliation(s)
| | | | | | - Gaetano Chiricolo
- Division of Cardiology, "Tor Vergata" University Hospital, Rome, Italy
| | - Gianluca Massaro
- Division of Cardiology, "Tor Vergata" University Hospital, Rome, Italy
| | - Giulio Russo
- Division of Cardiology, "Tor Vergata" University Hospital, Rome, Italy
| | - Stefano Sasso
- Division of Cardiology, "Tor Vergata" University Hospital, Rome, Italy
| | | | - Scipione Carerj
- Division of Cardiology, Policlinico "G. Martino", Messina, Italy
| | | | - Andrea Natale
- Division of Cardiology, "Tor Vergata" University Hospital, Rome, Italy
| | | | - Antonio Micari
- Division of Cardiology, Policlinico "G. Martino", Messina, Italy
| |
Collapse
|
|
3
|
Zheng X, Tan L, Cheng Y, Huang D. Predictive value of blood urea nitrogen to creatinine ratio and estimated plasma volume status in heart failure. BMC Cardiovasc Disord 2025; 25:282. [PMID: 40221652 PMCID: PMC11993939 DOI: 10.1186/s12872-025-04717-5] [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: 11/14/2024] [Accepted: 03/28/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND The blood urea nitrogen to creatinine ratio (BCR) and estimated plasma volume status (ePVS) may be prognostic markers in heart failure (HF), but their combined efficacy is unclear. This research aims to determine the prognostic utility of BCR and ePVS in critically ill HF patients in the intensive care unit. METHODS Data from the MIMIC-IV database were analyzed. ePVS was calculated using hemoglobin and hematocrit levels with Strauss-derived Duarte method. The primary outcome was 1-year all-cause mortality (ACM). Receiver operating characteristic (ROC) curves identified cutoff values for BCR and ePVS. To assess the connection between BCR, ePVS, and 1-year ACM, the Kaplan-Meier (KM) method, Cox proportional hazards models, subgroup analysis, and limited cubic spline were employed. Harrell's C statistic evaluated predictive power. RESULTS Among 11,066 participants, optimal thresholds for mortality were BCR > 22.81 and ePVS > 7.16 ml/g. BCR demonstrated a non-linear J-shaped correlation with ACM, while ePVS displayed a linear relationship. Multivariate Cox analysis indicated higher level of BCR was linked to higher 1-year ACM (HR = 1.39, 95% CI: 1.30-1.49, P < 0.001), as was increased level of ePVS (HR = 1.09, 95% CI: 1.02-1.16, P = 0.012). Notably, HF patients with both high BCR and ePVS faced a significantly greater mortality risk than those with lower levels of both markers (HR = 1.54, 95% CI: 1.40-1.69, P < 0.001). Combining BCR and ePVS improved prognostic accuracy. CONCLUSIONS BCR and ePVS independently predict 1-year ACM in HF patients, with their combined use offering improved prognostic accuracy.
Collapse
Affiliation(s)
- Xiaoxue Zheng
- Department of Health Care, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Long Tan
- Health Service Department, Guard Bureau of the General Office of the Central Committee of the Communist Party of China, Beijing, 100017, China
| | - Yalin Cheng
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Dahai Huang
- Department of Health Care, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| |
Collapse
|
|
4
|
Montalto M, D’Ignazio F, Camilli S, Di Francesco S, Fedele M, Landi F, Gallo A. Heart Failure in Older Patients: An Update. J Clin Med 2025; 14:1982. [PMID: 40142790 PMCID: PMC11942917 DOI: 10.3390/jcm14061982] [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: 02/17/2025] [Revised: 03/08/2025] [Accepted: 03/10/2025] [Indexed: 03/28/2025] Open
Abstract
Heart failure (HF) is a clinical syndrome with high incidence and prevalence and high morbidity and death rate, even in the short term, representing a serious public health issue, mainly in older people. It is a growing cause for hospital admission in this age group, being frequently associated with several comorbidities, further aggravating the disease's course. Moreover, older HF patients are usually affected by clinical conditions, like frailty, malnutrition, and cachexia, which significantly impact the overall management of HF and need to be properly identified and treated. Diagnosing and managing HF in older patients may be very complicated and challenging. Although specific data on treatment of both acute and chronic HF in older subjects are limited and mainly extrapolated from large-scale clinical trials, the standard pharmacological management may be considered well-tolerated and generally safe. In any case, a personalized and tailored approach is mandatory and is based on severity of comorbidities, overall status, and prognosis, above all in frailer and more comorbid subjects, due to the higher rate of drug interactions, side effects, and therapy discontinuation in this population. In this scenario, palliative care has become a fundamental part of HF management in the elderly in order to improve their care and the quality of life. Moreover, an increasing number of promising pharmacological options deserve further investigation in order to support clinicians in optimizing management of comorbid and frailer patients. In this work, we provide detailed and updated insight into clinical, therapeutic, and prognostic features of both acute and chronic HF in the older population.
Collapse
Affiliation(s)
- Massimo Montalto
- Department of Geriatrics, Orthopedics and Rheumatology, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy; (M.M.); (F.L.)
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (F.D.); (S.C.); (S.D.F.); (M.F.)
| | - Federica D’Ignazio
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (F.D.); (S.C.); (S.D.F.); (M.F.)
| | - Sara Camilli
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (F.D.); (S.C.); (S.D.F.); (M.F.)
| | - Silvino Di Francesco
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (F.D.); (S.C.); (S.D.F.); (M.F.)
| | - Marco Fedele
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (F.D.); (S.C.); (S.D.F.); (M.F.)
| | - Francesco Landi
- Department of Geriatrics, Orthopedics and Rheumatology, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy; (M.M.); (F.L.)
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (F.D.); (S.C.); (S.D.F.); (M.F.)
| | - Antonella Gallo
- Department of Geriatrics, Orthopedics and Rheumatology, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy; (M.M.); (F.L.)
| |
Collapse
|
|
5
|
Lei J, Zhang Z, Li Y, Wu Z, Pu H, Xu Z, Yang X, Wang R, Qiu P, Chen T, Lu X. Fluid balance and clinical outcomes in patients with aortic dissection: a retrospective case-control study based on ICU databases. BMJ Open 2025; 15:e083933. [PMID: 39922586 PMCID: PMC11808867 DOI: 10.1136/bmjopen-2024-083933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 09/30/2024] [Indexed: 02/10/2025] Open
Abstract
OBJECTIVES Aortic dissection (AD) is a life-threatening condition that requires intensive care and management. This paper explores the role of fluid management in the clinical care of AD patients, which has been unclear despite the substantial existing research that has been conducted on the treatment of AD. DESIGN A retrospective case-control study using data for AD patients from public databases. SETTING Two public intensive care unit (ICU) databases with hospital courses from the USA, Medical Information Mart for Intensive Care (MIMIC)-IV critical care dataset and the eICU Collaborative Research Database, with data from 2008 to 2019. PARTICIPANTS A total of 751 adult AD patients with detailed fluid management records from two databases were included. INTERVENTIONS The mean 24-hour intake and output were calculated by dividing the total amount of intake and output by the number of days in the ICU, respectively. The mean 24-hour fluid balance was generated by subtracting the output from the intake. OUTCOME MEASURES The relationship between the mean 24-hour fluid management and all-cause in-hospital death was assessed through univariate and multivariable regression analyses. RESULTS A positive correlation was found between mean 24-hour fluid intake and in-hospital mortality among AD patients (OR 1.029, 95% CI (1.018, 1.041), p<0.001), whereas a negative correlation was revealed between mean 24-hour fluid output and in-hospital mortality (OR 0.941, 95% CI (0.914, 0.968), p<0.001). A similar result was found for mean 24-hour fluid balance (OR 1.030, 95% CI (1.019, 1.042), p<0.001), and the cut-off was selected to be 5.12 dL (AUC=0.778, OR 3.066, 95% CI (1.634, 5.753), p<0.001). CONCLUSIONS This study stresses the importance of fluid balance in the clinical care of AD patients and provides new insights for optimising fluid management and monitoring strategies beyond the conventional focus on blood pressure and heart rate management.
Collapse
Affiliation(s)
- Jiahao Lei
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Zhuojing Zhang
- Department of Economics, University of Waterloo, Waterloo, Ontario, Canada
- Big Data Research Lab, University of Waterloo, Waterloo, Ontario, Canada
| | - Yixuan Li
- Big Data Research Lab, University of Waterloo, Waterloo, Ontario, Canada
- Department of Anthropology, Economics and Political Science, MacEwan University, Edmonton, Alberta, Canada
| | - Zhaoyu Wu
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Hongji Pu
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Zhijue Xu
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Xinrui Yang
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Ruihua Wang
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Peng Qiu
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Tao Chen
- Department of Economics, University of Waterloo, Waterloo, Ontario, Canada
- Big Data Research Lab, University of Waterloo, Waterloo, Ontario, Canada
- Senior Research Fellow, Labor and Worklife Program, Harvard University, Cambridge, Massachusetts, USA
| | - Xinwu Lu
- Department of Vascular Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| |
Collapse
|
|
6
|
Çetin Güvenç R, Koç Ada S, Güvenç TS, Çelik FB, Polat Ocaklı E, Al Arfaj AA, Güllü H, Özer N, Çekmen MB, Çalışkan M. Neurohormonal activation pattern in patients with atrial septal defect. Sci Rep 2024; 14:29980. [PMID: 39622872 PMCID: PMC11612160 DOI: 10.1038/s41598-024-78950-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 11/05/2024] [Indexed: 12/06/2024] Open
Abstract
Atrial septal defects (ASD) divert flow from systemic to pulmonary circulation, and some degree of plasma volume expansion and neurohormonal activation are necessary to maintain the effective circulatory volume. The aim of the present study was to understand the patterns of neurohormonal activation in ASD patients. 16 ASD patients and 10 controls were enrolled. Fasting blood samples were collected prior to procedure and 48 h after defect closure. At baseline, renin (185.0(79.0-437.0 vs. 79.4(60.8-110.0), p = 0.04), aldosterone (20.2 ± 7.6 vs. 11.7 ± 2.8, p < 0.001), copeptin (43.6 ± 27.5 vs. 16.4 ± 8.7, p = 0.002) and both natriuretic peptides were higher in ASD patients, while noradrenaline (113.0 ± 61.3 vs. 178.0 ± 49.4, p = 0.009) and endothelin-1 (2.93 ± 2.00 vs. 5.06 ± 1.25, p = 0.006) were higher in controls. After ASD closure, only NT-proBNP reduced significantly (p = 0.02). There were negative correlations between defect area with noradrenaline (r=-0.73, p = 0.002) and with endothelin-1 (r=-0.59, p = 0.02). Present findings suggest that in patients with an ASD, there is an increase in neurohormones that are related to regulation of plasma volume (aldosterone and arginine vasopressin) with simultaneous reductions in neurohormones related to vasoconstriction in systemic and pulmonary beds (noradrenaline and endothelin-1).
Collapse
Grants
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
- 24.02.2022/5 Okan University, Turkey
Collapse
Affiliation(s)
- Rengin Çetin Güvenç
- Okan Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Tepeören Mahallesi Tuzla Kampüsü, İstanbul Okan Üniversitesi, 34959, Tuzla, İstanbul, Turkey.
| | - Saniye Koç Ada
- Biyokimya Anabilim Dalı, Medeniyet Üniversitesi Tıp Fakültesi, İstanbul, Turkey
| | - Tolga Sinan Güvenç
- Kardiyoloji Anabilim Dalı, İstinye Üniversitesi Tıp Fakültesi, İstabul, Turkey
| | | | | | - Abdullah Ayar Al Arfaj
- Okan Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Tepeören Mahallesi Tuzla Kampüsü, İstanbul Okan Üniversitesi, 34959, Tuzla, İstanbul, Turkey
| | - Hakan Güllü
- Kardiyoloji Kliniği, Etlik Şehir Hastanesi, Ankara, Turkey
| | - Nihat Özer
- Okan Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Tepeören Mahallesi Tuzla Kampüsü, İstanbul Okan Üniversitesi, 34959, Tuzla, İstanbul, Turkey
| | - Mustafa Baki Çekmen
- Biyokimya Anabilim Dalı, Medeniyet Üniversitesi Tıp Fakültesi, İstanbul, Turkey
| | - Mustafa Çalışkan
- Medeniyet Üniversitesi Kardiyoloji Anabilim Dalı, İstanbul, Turkey
| |
Collapse
|
|
7
|
Sohal S, Uppal D, Mathai SV, Wats K, Uppal NN. Acute Cardiorenal Syndrome: An Update. Cardiol Rev 2024; 32:489-498. [PMID: 36883827 DOI: 10.1097/crd.0000000000000532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
The complex dynamic pathophysiological interplay between the heart and kidney causes a vicious cycle of worsening renal and/or cardiovascular function. Acute decompensated heart failure causing worsening renal function defines Type 1 cardiorenal syndrome (CRS). Altered hemodynamics coupled with a multitude of nonhemodynamic factors namely pathological activation of the renin angiotensin aldosterone system and systemic inflammatory pathways mechanistically incite CRS type 1. A multipronged diagnostic approach utilizing laboratory markers, noninvasive and/or invasive modalities must be implemented to enable timely initiation of effective treatment strategies. In this review, we discuss the pathophysiology, diagnosis, and emerging treatment options for CRS type 1.
Collapse
Affiliation(s)
- Sumit Sohal
- From the Division of Cardiovascular Diseases, Department of Medicine, RWJ-BH Newark Beth Israel Medical Center, Newark, NJ
| | - Dipan Uppal
- Department of Cardiovascular Diseases, Cleveland Clinic Florida, Weston, FL
| | | | - Karan Wats
- Division of Cardiovascular Diseases, Department of Medicine, New York-Presbyterian/Columbia University Irving Medical Center, New York, NY
| | - Nupur N Uppal
- Division of Kidney Diseases and Hypertension, Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY
| |
Collapse
|
|
8
|
Biegus J, Cotter G, Metra M, Ponikowski P. Decongestion in acute heart failure: Is it time to change diuretic-centred paradigm? Eur J Heart Fail 2024; 26:2094-2106. [PMID: 39169731 DOI: 10.1002/ejhf.3423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/18/2024] [Accepted: 07/25/2024] [Indexed: 08/23/2024] Open
Abstract
Congestion is a common cause of clinical deterioration and the most common clinical presentation at admission in acute heart failure (HF). Therefore, finding effective and sustainable ways to alleviate congestion has become a crucial goal for treating HF patients. Congestion is a result of complex underlying pathophysiology; therefore, it is not a direct cause of the disease but its consequence. Any therapy that directly promotes sodium/water removal only, thus targeting only clinical symptoms, neither modifies the natural course of the disease nor improves prognosis. This review aims to provide a comprehensive evaluation of the current decongestive therapies and propose a new (not diuretic-centred) paradigm of long-term congestion management in HF that attempts to correct the underlying pathophysiology, thus improving congestion, preventing its development, and favourably altering the natural course of the disease rather than merely treating its symptoms.
Collapse
Affiliation(s)
- Jan Biegus
- Institute of Heart Diseases, Wroclaw Medical University, Wrocław, Poland
| | - Gad Cotter
- Momentum Research, Inc., Chapel Hill, NC, USA
- U 942 Inserm MASCOT, Paris, France
| | - Marco Metra
- Cardiology, ASST Spedali Civili and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Wrocław, Poland
| |
Collapse
|
|
9
|
Boehmer AA, Schubert T, Rothe M, Keim C, Wiedenmann L, Ruckes C, von Stuelpnagel L, Theurl F, Schreinlechner M, Dobre BC, Kaess BM, Bauer A, Ehrlich JR. Angiotensin Receptor-Neprilysin Inhibitor Is Associated With Improved Cardiac Autonomic Function in Heart Failure. J Am Heart Assoc 2024; 13:e033538. [PMID: 39082399 PMCID: PMC11964052 DOI: 10.1161/jaha.123.033538] [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: 11/15/2023] [Accepted: 05/24/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied. METHODS AND RESULTS This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement. CONCLUSIONS Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by "volume unloading" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction. REGISTRATION URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.
Collapse
Affiliation(s)
| | - Tim Schubert
- Division of CardiologySt. Josefs‐Hospital WiesbadenWiesbadenGermany
| | - Moritz Rothe
- Division of CardiologySt. Josefs‐Hospital WiesbadenWiesbadenGermany
| | - Christoph Keim
- Division of CardiologySt. Josefs‐Hospital WiesbadenWiesbadenGermany
| | - Lilli Wiedenmann
- Division of CardiologySt. Josefs‐Hospital WiesbadenWiesbadenGermany
| | - Christian Ruckes
- University Medical Center MainzInterdisciplinary Center for Clinical TrialsMainzGermany
| | | | - Fabian Theurl
- Division of CardiologyMedical University of InnsbruckInnsbruckAustria
| | | | - Bianca C. Dobre
- Division of CardiologySt. Josefs‐Hospital WiesbadenWiesbadenGermany
| | | | - Axel Bauer
- Division of CardiologyMedical University of InnsbruckInnsbruckAustria
| | | |
Collapse
|
|
10
|
Wu L, Rodriguez M, El Hachem K, Krittanawong C. Diuretic Treatment in Heart Failure: A Practical Guide for Clinicians. J Clin Med 2024; 13:4470. [PMID: 39124738 PMCID: PMC11313642 DOI: 10.3390/jcm13154470] [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: 07/09/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
Congestion and fluid retention are the hallmarks of decompensated heart failure and the major reason for the hospitalization of patients with heart failure. Diuretics have been used in heart failure for decades, and they remain the backbone of the contemporary management of heart failure. Loop diuretics is the preferred diuretic, and it has been given a class I recommendation by clinical guidelines for the relief of congestion symptoms. Although loop diuretics have been used virtually among all patients with acute decompensated heart failure, there is still very limited clinical evidence to guide the optimized diuretics use. This is a sharp contrast to the rapidly growing evidence of the rest of the guideline-directed medical therapy of heart failure and calls for further studies. The loop diuretics possess a unique pharmacology and pharmacokinetics that lay the ground for different strategies to increase diuretic efficiency. However, many of these approaches have not been evaluated in randomized clinical trials. In recent years, a stepped and protocolized diuretics dosing has been suggested to have superior benefits over an individual clinician-based strategy. Diuretic resistance has been a major challenge to decongestion therapy for patients with heart failure and is associated with a poor clinical prognosis. Recently, therapy options have emerged to help overcome diuretic resistance to loop diuretics and have been evaluated in randomized clinical trials. In this review, we aim to provide a comprehensive review of the pharmacology and clinical use of loop diuretics in the context of heart failure, with attention to its side effects, and adjuncts, as well as the challenges and future direction.
Collapse
Affiliation(s)
- Lingling Wu
- Cardiovascular Division, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Mario Rodriguez
- John T. Milliken Department of Medicine, Division of Cardiovascular Disease, Section of Advanced Heart Failure and Transplant, Barnes-Jewish Hospital, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Karim El Hachem
- Division of Nephrology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY 10029, USA
| | - Chayakrit Krittanawong
- Section of Cardiology, Cardiology Division, NYU Langone Health and NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
| |
Collapse
|
|
11
|
Schuermans A, Verbrugge FH. Decongestion (instead of ultrafiltration?). Curr Opin Cardiol 2024; 39:188-195. [PMID: 38362936 DOI: 10.1097/hco.0000000000001124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
PURPOSE OF REVIEW To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF). RECENT FINDINGS While loop diuretic therapy has remained the backbone of decongestive treatment in AHF, multiple randomized clinical trials suggest that early combination with other diuretic classes or molecules with diuretic properties should be considered. Mineralocorticoid receptor antagonists and sodium-glucose co-transporter-2 inhibitors are disease-modifying drugs in heart failure that favourably influence prognosis early on, advocating their start as soon as possible in the absence of any compelling contraindications. Short-term upfront use of acetazolamide in adjunction to intravenous loop diuretic therapy relieves congestion faster, avoids diuretic resistance, and may shorten hospitalization length. Thiazide-like diuretics remain a good option to break diuretic resistance. Currently, ultrafiltration in AHF remains mainly reserved for patient with an inadequate response to pharmacological treatment. SUMMARY In most patients with AHF, decongestion can be achieved effectively and safely through combination diuretic therapies. Appropriate diuretic therapy may shorten hospitalization length and improve quality of life, but has not yet proven to reduce death or heart failure readmissions. Ultrafiltration currently has a limited role in AHF, mainly as bail-out strategy, but evidence for a more upfront use remains inconclusive.
Collapse
Affiliation(s)
| | - Frederik H Verbrugge
- Centre for Cardiovascular Diseases, University Hospital Brussels
- Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Jette, Belgium
| |
Collapse
|
|
12
|
Ge T, Song S, Li S, Yu X, Shao L, Tong J. Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis. Cardiovasc Diagn Ther 2023; 13:994-1002. [PMID: 38162113 PMCID: PMC10753246 DOI: 10.21037/cdt-23-323] [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: 07/29/2023] [Accepted: 10/27/2023] [Indexed: 01/03/2024]
Abstract
Background Obstructive sleep apnea syndrome (OSAS) combined with heart failure (HF) has become a serious disease that threatens human health. Therapeutic interventions targeting OSAS have been shown to improve outcomes in patients with HF, so the identification of severe OSAS in HF is critical. Carbohydrate antigen 125 (CA125) is associated with inflammation and volume overload. The levels of CA125 are elevated in the serum of patients with HF and might be further elevated in patients with HF and OSAS. The aim of this study was to measure CA125 levels in patients with HF with and without OSAS and to analyze affecting factors. Methods In this single-center retrospective cohort study, a total of 95 patients diagnosed with HF hospitalized in Zhongda Hospital from April 2021 to April 2022 were recruited, including 55 patients with OSAS and 40 patients without OSAS. Participants with a history of central sleep apnea syndrome, severe chronic obstructive pulmonary disease, tumors, severe infection, or who were pregnant were excluded. The histories of the participants were recorded, and laboratory examinations were performed. Binary logistic regression analysis was performed to determine the relationship between serum CA125 levels and OSAS in patients with HF. Results The serum CA125 levels were higher in the HF + OSAS group than in the HF group (29.60 vs. 9.68 U/mL, P<0.001). According to the univariate analysis, CA125 (>35 U/mL) was significantly related to pleural effusion, acute HF, apnea-hypopnea index (AHI), left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Finally, the AHI demonstrated statistical significance in multiple analyses (OR 1.070, 95% CI: 1.019-1.124, P=0.006). Spearman rank correlation coefficient analysis showed that CA125 was positively correlated with AHI, and Ln(CA125) (Ln is the natural logarithm based on e) gradually increased with increasing AHI (r=0.551, P<0.0001). Conclusions The levels of CA125 were further increased in patients with HF and OSAS, and CA125 (>35 U/mL) was positively correlated with AHI. As a biomarker associated with inflammation and congestion, serum CA125 may have certain value in the diagnosis of patients with HF combined with OSAS.
Collapse
Affiliation(s)
- Tiantian Ge
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Songsong Song
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Shengnan Li
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiaojin Yu
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Liangfa Shao
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jiayi Tong
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| |
Collapse
|
|
13
|
Chatterjee E, Rodosthenous RS, Kujala V, Gokulnath P, Spanos M, Lehmann HI, de Oliveira GP, Shi M, Miller-Fleming TW, Li G, Ghiran IC, Karalis K, Lindenfeld J, Mosley JD, Lau ES, Ho JE, Sheng Q, Shah R, Das S. Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system. JCI Insight 2023; 8:e165172. [PMID: 37707956 PMCID: PMC10721327 DOI: 10.1172/jci.insight.165172] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 09/08/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUNDCardiorenal syndrome (CRS) - renal injury during heart failure (HF) - is linked to high morbidity. Whether circulating extracellular vesicles (EVs) and their RNA cargo directly impact its pathogenesis remains unclear.METHODSWe investigated the role of circulating EVs from patients with CRS on renal epithelial/endothelial cells using a microfluidic kidney-on-chip (KOC) model. The small RNA cargo of circulating EVs was regressed against serum creatinine to prioritize subsets of functionally relevant EV-miRNAs and their mRNA targets investigated using in silico pathway analysis, human genetics, and interrogation of expression in the KOC model and in renal tissue. The functional effects of EV-RNAs on kidney epithelial cells were experimentally validated.RESULTSRenal epithelial and endothelial cells in the KOC model exhibited uptake of EVs from patients with HF. HF-CRS EVs led to higher expression of renal injury markers (IL18, LCN2, HAVCR1) relative to non-CRS EVs. A total of 15 EV-miRNAs were associated with creatinine, targeting 1,143 gene targets specifying pathways relevant to renal injury, including TGF-β and AMPK signaling. We observed directionally consistent changes in the expression of TGF-β pathway members (BMP6, FST, TIMP3) in the KOC model exposed to CRS EVs, which were validated in epithelial cells treated with corresponding inhibitors and mimics of miRNAs. A similar trend was observed in renal tissue with kidney injury. Mendelian randomization suggested a role for FST in renal function.CONCLUSIONPlasma EVs in patients with CRS elicit adverse transcriptional and phenotypic responses in a KOC model by regulating biologically relevant pathways, suggesting a role for EVs in CRS.TRIAL REGISTRATIONClinicalTrials.gov NCT03345446.FUNDINGAmerican Heart Association (AHA) (SFRN16SFRN31280008); National Heart, Lung, and Blood Institute (1R35HL150807-01); National Center for Advancing Translational Sciences (UH3 TR002878); and AHA (23CDA1045944).
Collapse
Affiliation(s)
- Emeli Chatterjee
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Rodosthenis S. Rodosthenous
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
| | | | - Priyanka Gokulnath
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Michail Spanos
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Helge Immo Lehmann
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | | | | | - Guoping Li
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Ionita Calin Ghiran
- Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Katia Karalis
- Emulate, Inc., Boston, Massachusetts, USA
- Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA
| | - JoAnn Lindenfeld
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jonathan D. Mosley
- Department of Biomedical Informatics and
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Emily S. Lau
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jennifer E. Ho
- Cardiovascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Ravi Shah
- Vanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Saumya Das
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| |
Collapse
|
|
14
|
Voicehovska JG, Trumpika D, Voicehovskis VV, Bormane E, Bušmane I, Grigane A, Moreino E, Lejnieks A. Cardiovascular Consequences of Acute Kidney Injury: Treatment Options. Biomedicines 2023; 11:2364. [PMID: 37760806 PMCID: PMC10526099 DOI: 10.3390/biomedicines11092364] [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: 07/31/2023] [Revised: 08/16/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023] Open
Abstract
Soon after haemodialysis was introduced into clinical practice, a high risk of cardiac death was noted in end-stage renal disease. However, only in the last decade has it become clear that any renal injury, acute or chronic, is associated with high overall and cardiovascular lethality. The need for early recognition of kidney damage in cardiovascular pathology to assess risk and develop tactics for patient management contributed to the emergence of the concept of the "cardiorenal syndrome" (CRS). CRS is a pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction of one of these organs leads to acute or chronic dysfunction of the other. The beneficial effect of ultrafiltration as a component of renal replacement therapy (RRT) is due to the elimination of hyperhydration, which ultimately affects the improvement in cardiac contractile function. This review considers the theoretical background, current status of CRS, and future potential of RRT, focusing on the benefits of ultrafiltration as a therapeutic option.
Collapse
Affiliation(s)
- Julija G. Voicehovska
- Department of Internal Diseases, Medical Faculty, Riga Stradins University, LV-1007 Riga, Latvia; (D.T.); (V.V.V.); (E.M.); (A.L.)
- Department of Kidney Diseases and Renal Replacement Therapy, Riga East Clinical University Hospital, LV-1038 Riga, Latvia; (E.B.); (I.B.); (A.G.)
| | - Dace Trumpika
- Department of Internal Diseases, Medical Faculty, Riga Stradins University, LV-1007 Riga, Latvia; (D.T.); (V.V.V.); (E.M.); (A.L.)
- Department of Kidney Diseases and Renal Replacement Therapy, Riga East Clinical University Hospital, LV-1038 Riga, Latvia; (E.B.); (I.B.); (A.G.)
| | - Vladimirs V. Voicehovskis
- Department of Internal Diseases, Medical Faculty, Riga Stradins University, LV-1007 Riga, Latvia; (D.T.); (V.V.V.); (E.M.); (A.L.)
| | - Eva Bormane
- Department of Kidney Diseases and Renal Replacement Therapy, Riga East Clinical University Hospital, LV-1038 Riga, Latvia; (E.B.); (I.B.); (A.G.)
| | - Inara Bušmane
- Department of Kidney Diseases and Renal Replacement Therapy, Riga East Clinical University Hospital, LV-1038 Riga, Latvia; (E.B.); (I.B.); (A.G.)
| | - Anda Grigane
- Department of Kidney Diseases and Renal Replacement Therapy, Riga East Clinical University Hospital, LV-1038 Riga, Latvia; (E.B.); (I.B.); (A.G.)
| | - Eva Moreino
- Department of Internal Diseases, Medical Faculty, Riga Stradins University, LV-1007 Riga, Latvia; (D.T.); (V.V.V.); (E.M.); (A.L.)
| | - Aivars Lejnieks
- Department of Internal Diseases, Medical Faculty, Riga Stradins University, LV-1007 Riga, Latvia; (D.T.); (V.V.V.); (E.M.); (A.L.)
- Riga East Clinical University Hospital, LV-1038 Riga, Latvia
| |
Collapse
|
|
15
|
Brethel S, Locker S, Girens R, Rivera P, Meurs K, Adin D. The effect of taurine supplementation on the renin-angiotensin-aldosterone system of dogs with congestive heart failure. Sci Rep 2023; 13:10700. [PMID: 37400490 DOI: 10.1038/s41598-023-37978-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 06/30/2023] [Indexed: 07/05/2023] Open
Abstract
The role of taurine in the treatment of congestive heart failure (CHF) in dogs without systemic deficiency is unexplored. Taurine might have beneficial cardiac effects aside from deficit replacement. We hypothesized that oral taurine supplementation administered to dogs with naturally-occurring CHF would suppress the renin-angiotensin aldosterone system (RAAS). Oral taurine was administered to 14 dogs with stable CHF. Serum biochemical variables, blood taurine concentrations, and comprehensive analysis of RAAS variables were compared before and 2 weeks after taurine supplementation added to background furosemide and pimobendan therapy for CHF. Whole blood taurine concentrations increased after supplementation (median 408 nMol/mL, range 248-608 before and median 493 nMol/mL, range 396-690 after; P = .006). Aldosterone to angiotensin II ratio (AA2) was significantly decreased after taurine supplementation (median 1.00, range 0.03-7.05 before and median 0.65, range 0.01-3.63 after; P = .009), but no other RAAS components significantly differed between timepoints. A subset of dogs showed marked decreases in RAAS metabolites after supplementation and these dogs were more likely to have been recently hospitalized for CHF treatment than dogs that did not show marked decreases in classical RAAS metabolites. Overall, taurine only lowered AA2 in this group of dogs, however, response heterogeneity was noted, with some dogs showing RAAS suppression.
Collapse
Affiliation(s)
- Sara Brethel
- College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
- Charlotte Animal Referral and Emergency, Charlotte, NC, USA
| | - Seth Locker
- College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
| | - Renee Girens
- College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
- Summit Veterinary Referral Center, Tacoma, WA, USA
| | - Paulo Rivera
- College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
| | - Kathryn Meurs
- College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
| | - Darcy Adin
- College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
| |
Collapse
|
|
16
|
McCallum W, Sarnak MJ. Cardiorenal Syndrome in the Hospital. Clin J Am Soc Nephrol 2023; 18:933-945. [PMID: 36787124 PMCID: PMC10356127 DOI: 10.2215/cjn.0000000000000064] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 12/22/2022] [Indexed: 01/22/2023]
Abstract
The cardiorenal syndrome refers to a group of complex, bidirectional pathophysiological pathways involving dysfunction in both the heart and kidney. Upward of 60% of patients admitted for acute decompensated heart failure have CKD, as defined by an eGFR of <60 ml/min per 1.73 m 2 . CKD, in turn, is one of the strongest risk factors for mortality and cardiovascular events in acute decompensated heart failure. Although not well understood, the mechanisms in the cardiorenal syndrome include venous congestion, arterial underfilling, neurohormonal activation, inflammation, and endothelial dysfunction. Arterial underfilling may lead to activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, leading to sodium reabsorption and vasoconstriction. Venous congestion likely also mediates and perpetuates these maladaptive pathways. To rule out intrinsic kidney disease that is distinct from the cardiorenal syndrome, one should obtain a careful history, review longitudinal eGFR trends, assess albuminuria and proteinuria, and review the urine sediment and kidney imaging. The hallmark of the cardiorenal syndrome is intense sodium avidity and diuretic resistance, often requiring a combination of diuretics with varying pharmacological targets, and monitoring of urinary response to guide escalations in therapy. Invasive means of decongestion may be required including ultrafiltration or KRT such as peritoneal dialysis, which is often better tolerated from a hemodynamic perspective than intermittent hemodialysis. Strategies for increasing forward perfusion in states of low cardiac output and cardiogenic shock may include afterload reduction and inotropes and, in the most severe cases, mechanical circulatory support devices, many of which have kidney-specific considerations.
Collapse
Affiliation(s)
- Wendy McCallum
- Division of Nephrology, Tufts Medical Center, Boston, Massachusetts
| | | |
Collapse
|
|
17
|
Weng YF, Chen CY, Hwang SJ, Huang YB. Evaluation of sodium-glucose cotransporter 2 inhibitors for renal prognosis and mortality in diabetes patients with heart failure on diuretics. Kaohsiung J Med Sci 2023; 39:416-425. [PMID: 36625282 DOI: 10.1002/kjm2.12635] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 11/25/2022] [Accepted: 12/01/2022] [Indexed: 01/11/2023] Open
Abstract
Previous studies about renal protection of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) on diuretics were still limited. The goal of the study is to survey the efficacy of SGLT2i to reduce all-cause mortality and renal impairments in patients with T2DM and HF using diuretics. The retrospective cohort study was analyzed from Kaohsiung Medical University Hospital Research Database (KMUHRD) in Taiwan. Adults with T2DM and HF using any diuretics at least 28 days during 2016-2018 were enrolled and then divided into the SGLT2i group and the non-SGLT2i group. Propensity score matching was used to balance baseline characteristics between the two groups. The primary outcome was all-cause mortality. Secondary outcomes contained dialysis occurrence, renal progression, and acute kidney injury (AKI). After 1:1 matching, there were 183 patients in each group respectively. When compared with the non-SGLT2i group, the SGLT2i group had significantly lower all-cause mortality (hazard ratios [HR]: 0.49, 95% CI 0.29-0.83, p = 0.008) and reduction of renal progression (HR: 0.30, 95% CI 0.12-0.75, p = 0.010). SGLT2i showed the trend to decrease dialysis occurrence (HR: 0.83, 95% CI 0.20-3.47, p = 0.797) and an increase in AKI (HR: 1.38, 95% CI 0.67-2.87, p = 0.383) but without significance. SGLT2 inhibitors were associated with reduced all-cause mortality and less renal progression with significance in T2DM patients with HF on diuretics.
Collapse
Affiliation(s)
- Yi-Fang Weng
- Master Degree Program in Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Chung-Yu Chen
- Master Degree Program in Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shang-Jyh Hwang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yaw-Bin Huang
- Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| |
Collapse
|
|
18
|
Prastaro M, Nardi E, Paolillo S, Santoro C, Parlati ALM, Gargiulo P, Basile C, Buonocore D, Esposito G, Filardi PP. Cardiorenal syndrome: Pathophysiology as a key to the therapeutic approach in an under-diagnosed disease. JOURNAL OF CLINICAL ULTRASOUND : JCU 2022; 50:1110-1124. [PMID: 36218199 PMCID: PMC9828083 DOI: 10.1002/jcu.23265] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 06/13/2022] [Accepted: 06/20/2022] [Indexed: 06/09/2023]
Abstract
Cardiorenal syndrome is a clinical condition that impacts both the heart and the kidneys. One organ's chronic or acute impairment can lead to the other's chronic or acute dysregulation. The cardiorenal syndrome has been grouped into five subcategories that describe the etiology, pathophysiology, duration, and pattern of cardiac and renal dysfunction. This classification reflects the large spectrum of interrelated dysfunctions and underlines the bidirectional nature of heart-kidney interactions. However, more evidence is needed to apply these early findings in medical practice. Understanding the relationship between these two organs during each organ's impairment has significant clinical implications that are relevant for therapy in both chronic and acute conditions. The epidemiology, definition, classification, pathophysiology, therapy, and outcome of each form of cardiorenal syndrome are all examined in this review.
Collapse
Affiliation(s)
- Maria Prastaro
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Ermanno Nardi
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Stefania Paolillo
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Ciro Santoro
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Antonio L. M. Parlati
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Paola Gargiulo
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Christian Basile
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Davide Buonocore
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | - Giovanni Esposito
- Department of Advanced Biomedical SciencesUniversity of Naples Federico IINaplesItaly
| | | |
Collapse
|
|
19
|
Abstract
Fluid volume homeostasis in health and heart failure (HF) requires a complex interaction of 2 systems, the intravascular and interstitial-lymphatic circulations. With the development of HF both the intravascular and interstitial compartments undergo variable degrees of volume remodeling which can include significant expansion. This reflects the impact of multiple pathophysiologic mechanisms on both fluid compartments which initially play a compensatory role to stabilize intravascular circulatory integrity but with progression in HF can evolve to produce the various manifestations of volume overload and clinical HF congestion. The intent of this review is to help enhance recognition of the pathophysiologic and clinical importance of the interlinked roles of these 2 circulatory systems in volume regulation and chronic HF. It would also be hoped that a better understanding of the interacting functions of the intravascular and interstitial-lymphatic fluid compartments can potentially aid development of novel management strategies particularly addressing the generally undertargeted interstitial-lymphatic system and help bring such approaches forward through a more integrated view of these 2 circulatory systems.
Collapse
Affiliation(s)
- Wayne L Miller
- Division of Circulatory Failure, Department of Cardiovascular Medicine Mayo Clinic Rochester MN
| |
Collapse
|
|
20
|
Sullivan RD, McCune ME, Hernandez M, Reed GL, Gladysheva IP. Suppression of Cardiogenic Edema with Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure with Reduced Ejection Fraction: Mechanisms and Insights from Pre-Clinical Studies. Biomedicines 2022; 10:2016. [PMID: 36009562 PMCID: PMC9405937 DOI: 10.3390/biomedicines10082016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 11/17/2022] Open
Abstract
In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired cardiac function, pathological remodeling, chronic inflammation, endothelial dysfunction, neurohormonal activation, and altered nitric oxide-related pathways. Pre-clinical HFrEF studies have shown that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) stimulates natriuretic and osmotic/diuretic effects, improves overall cardiac function, attenuates maladaptive cardiac remodeling, and reduces chronic inflammation, oxidative stress, and endothelial dysfunction. Here, we review the mechanisms and effects of SGLT-2i therapy on cardiogenic edema in various models of HFrEF. Overall, the data presented suggest a high translational importance of these studies, and pre-clinical studies show that SGLT-2i therapy has a marked effect on suppressing the progression of HFrEF through multiple mechanisms, including those that affect the development of cardiogenic edema.
Collapse
Affiliation(s)
| | | | | | | | - Inna P. Gladysheva
- Department of Medicine, University of Arizona College of Medicine–Phoenix, Phoenix, AZ 85004, USA
| |
Collapse
|
|
21
|
Zhen Z, Liang W, Tan W, Dong B, Wu Y, Liu C, Xue R. Prognostic significance of blood urea nitrogen/creatinine ratio in chronic HFpEF. Eur J Clin Invest 2022; 52:e13761. [PMID: 35199851 DOI: 10.1111/eci.13761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/07/2022] [Accepted: 02/13/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The prognostic significance of blood urea nitrogen (BUN)/creatinine ratio specifically in chronic heart failure with preserved ejection fraction (HFpEF) patients remained unclear. We aimed to evaluate the association of BUN/creatinine ratio (baseline level and visit-to-visit variation) with the risk of adverse clinical outcomes among patients with chronic HFpEF. METHODS AND RESULTS This is a secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Of the enrolled 3445 participants in the TOPCAT trial, associations between BUN/creatinine and clinical outcomes were examined in a subset of 1521 (baseline measurements level) and 1453 (visit-to-visit variation) participants. A multivariable Cox proportional hazard model was used to assess the prognostic significance of BUN/creatinine ratio and BUN/creatinine ratio variation for the prespecified clinical outcomes. A higher BUN/creatinine ratio was associated with a higher risk of all-cause mortality (hazard ratio [HR] = 1.52, 95%CI, 1.21-1.91; p < .001) as well as cardiovascular disease mortality (HR = 1.83, 95%CI, 1.35-2.49; p < .001) in the fully adjusted model. Greater visit-to-visit variability in BUN/creatinine ratio tended to be independently associated with a higher risk of heart failure hospitalization and primary endpoint (p < .001 for both outcomes). Furthermore, those findings were consistent across participants stratified by the presence of chronic kidney disease at baseline. CONCLUSIONS Higher BUN/creatinine ratio and greater BUN/creatinine ratio variability are independently associated with adverse outcomes in HFpEF participants in the TOPCAT trial.
Collapse
Affiliation(s)
- Zhe Zhen
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.,National - Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China
| | - Weihao Liang
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.,National - Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China
| | - Weiping Tan
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bin Dong
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.,National - Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China
| | - Yuzhong Wu
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.,National - Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China
| | - Chen Liu
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.,National - Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China
| | - Ruicong Xue
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.,National - Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, China
| |
Collapse
|
|
22
|
Coiro S, Rastogi T, Girerd N. How and When to Use Lung Ultrasound in Patients with Heart Failure? Rev Cardiovasc Med 2022; 23:198. [PMID: 39077188 PMCID: PMC11273962 DOI: 10.31083/j.rcm2306198] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/08/2022] [Accepted: 04/14/2022] [Indexed: 07/31/2024] Open
Abstract
Pulmonary congestion is a critical finding in patients with heart failure (HF) that can be quantified by lung ultrasound (LUS) through B-line quantification, the latter of which can be easily measured by all commercially-available probes/ultrasound equipment. As such, LUS represents a useful tool for the assessment of patients with both acute and chronic HF. Several imaging protocols have been described in the literature according to different clinical settings. While most studies have been performed with either the 8 or 28 chest zone protocol, the 28-zone protocol is more time-consuming while the 8-zone protocol offers the best trade-off with no sizeable loss of information. In the acute setting, LUS has excellent value in diagnosing acute HF, which is superior to physical examination and chest X-ray, particularly in instances of diagnostic uncertainty. In addition to its diagnostic value, accumulating evidence over the last decade (mainly derived from ambulatory settings or at discharge from an acute HF hospitalisation) suggests that LUS can also represent a useful prognostic tool for predicting adverse outcome in both HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). It also allows real-time monitoring of pulmonary decongestion during treatment of acute HF. Additionally, LUS-guided therapy, when compared with usual care, has been shown to reduce the risk of HF hospitalisations at short- and mid-term follow-up. In addition, studies have shown good correlation between B-lines during exercise stress echocardiography and invasive, bio-humoral and echocardiographic indices of haemodynamic congestion; B-lines during exercise are also associated with worse prognosis in both HFrEF and HFpEF. Altogether, LUS represents a reliable and useful tool in the assessment of pulmonary congestion and risk stratification of HF patients throughout their entire journey (i.e., emergency department/acute settings, in-hospital management, discharge from acute HF hospitalisation, monitoring in the outpatient setting), with considerable diagnostic and prognostic implications.
Collapse
Affiliation(s)
- Stefano Coiro
- Cardiology Department, Santa Maria della Misericordia Hospital, 06129 Perugia, Italy
- Centre D'Investigation Clinique-Plurithématique Inserm CIC-P 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, 54500 Vandoeuvre lès Nancy, France
| | - Tripti Rastogi
- Centre D'Investigation Clinique-Plurithématique Inserm CIC-P 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, 54500 Vandoeuvre lès Nancy, France
| | - Nicolas Girerd
- Centre D'Investigation Clinique-Plurithématique Inserm CIC-P 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, 54500 Vandoeuvre lès Nancy, France
| |
Collapse
|
|
23
|
Gabbin B, Meraviglia V, Mummery CL, Rabelink TJ, van Meer BJ, van den Berg CW, Bellin M. Toward Human Models of Cardiorenal Syndrome in vitro. Front Cardiovasc Med 2022; 9:889553. [PMID: 35694669 PMCID: PMC9177996 DOI: 10.3389/fcvm.2022.889553] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/09/2022] [Indexed: 11/13/2022] Open
Abstract
Heart and kidney diseases cause high morbidity and mortality. Heart and kidneys have vital functions in the human body and, interestingly, reciprocally influence each other’s behavior: pathological changes in one organ can damage the other. Cardiorenal syndrome (CRS) is a group of disorders in which there is combined dysfunction of both heart and kidney, but its underlying biological mechanisms are not fully understood. This is because complex, multifactorial, and dynamic mechanisms are likely involved. Effective treatments are currently unavailable, but this may be resolved if more was known about how the disease develops and progresses. To date, CRS has actually only been modeled in mice and rats in vivo. Even though these models can capture cardiorenal interaction, they are difficult to manipulate and control. Moreover, interspecies differences may limit extrapolation to patients. The questions we address here are what would it take to model CRS in vitro and how far are we? There are already multiple independent in vitro (human) models of heart and kidney, but none have so far captured their dynamic organ-organ crosstalk. Advanced in vitro human models can provide an insight in disease mechanisms and offer a platform for therapy development. CRS represents an exemplary disease illustrating the need to develop more complex models to study organ-organ interaction in-a-dish. Human induced pluripotent stem cells in combination with microfluidic chips are one powerful tool with potential to recapitulate the characteristics of CRS in vitro. In this review, we provide an overview of the existing in vivo and in vitro models to study CRS, their limitations and new perspectives on how heart-kidney physiological and pathological interaction could be investigated in vitro for future applications.
Collapse
Affiliation(s)
- Beatrice Gabbin
- Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
| | - Viviana Meraviglia
- Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
| | - Christine L. Mummery
- Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
- Department of Applied Stem Cell Technologies, University of Twente, Enschede, Netherlands
| | - Ton J. Rabelink
- Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, Netherlands
| | - Berend J. van Meer
- Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
| | - Cathelijne W. van den Berg
- Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, Netherlands
| | - Milena Bellin
- Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
- Department of Biology, University of Padua, Padua, Italy
- Veneto Institute of Molecular Medicine, Padua, Italy
- *Correspondence: Milena Bellin, ,
| |
Collapse
|
|
24
|
Hernandez M, Sullivan RD, McCune ME, Reed GL, Gladysheva IP. Sodium-Glucose Cotransporter-2 Inhibitors Improve Heart Failure with Reduced Ejection Fraction Outcomes by Reducing Edema and Congestion. Diagnostics (Basel) 2022; 12:989. [PMID: 35454037 PMCID: PMC9024630 DOI: 10.3390/diagnostics12040989] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 03/30/2022] [Accepted: 04/12/2022] [Indexed: 02/07/2023] Open
Abstract
Pathological sodium-water retention or edema/congestion is a primary cause of heart failure (HF) decompensation, clinical symptoms, hospitalization, reduced quality of life, and premature mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) based therapies reduce hospitalization due to HF, improve functional status, quality, and duration of life in patients with HF with reduced ejection fraction (HFrEF) independently of their glycemic status. The pathophysiologic mechanisms and molecular pathways responsible for the benefits of SGLT-2i in HFrEF remain inconclusive, but SGLT-2i may help HFrEF by normalizing salt-water homeostasis to prevent clinical edema/congestion. In HFrEF, edema and congestion are related to compromised cardiac function. Edema and congestion are further aggravated by renal and pulmonary abnormalities. Treatment of HFrEF patients with SGLT-2i enhances natriuresis/diuresis, improves cardiac function, and reduces natriuretic peptide plasma levels. In this review, we summarize current clinical research studies related to outcomes of SGLT-2i treatment in HFrEF with a specific focus on their contribution to relieving or preventing edema and congestion, slowing HF progression, and decreasing the rate of rehospitalization and cardiovascular mortality.
Collapse
Affiliation(s)
- Michelle Hernandez
- Department of Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85004, USA; (M.H.); (R.D.S.); (M.E.M.); (G.L.R.)
- School of Medicine, Universidad Autónoma de Guadalajara, Zapopan 45129, Mexico
| | - Ryan D. Sullivan
- Department of Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85004, USA; (M.H.); (R.D.S.); (M.E.M.); (G.L.R.)
| | - Mariana E. McCune
- Department of Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85004, USA; (M.H.); (R.D.S.); (M.E.M.); (G.L.R.)
| | - Guy L. Reed
- Department of Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85004, USA; (M.H.); (R.D.S.); (M.E.M.); (G.L.R.)
| | - Inna P. Gladysheva
- Department of Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85004, USA; (M.H.); (R.D.S.); (M.E.M.); (G.L.R.)
| |
Collapse
|
|
25
|
Ke B, Tan X, Ren L, Fan Y, Zhang Y, Li F, Sun Q, Liu T, Jia L, Wang Y, Du J. Aldosterone dysregulation predicts the risk of mortality and rehospitalization in heart failure with a preserved ejection fraction. SCIENCE CHINA. LIFE SCIENCES 2022; 65:631-642. [PMID: 34258711 DOI: 10.1007/s11427-021-1945-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/14/2021] [Indexed: 10/20/2022]
Abstract
Serum aldosterone is associated with cardiac remodeling, which contributes to morbidity and mortality in heart failure (HF); however, the prognostic value of aldosterone in HF with a preserved ejection fraction (HFpEF) is unclear. We used liquid chromatography-tandem mass spectrometry to quantify serum aldosterone in 873 patients with HFpEF in a Registry Study of Biomarkers for HF. The retrospective study was conducted at Beijing Anzhen Hospital from May 2017 to October 2019. The primary endpoint was a composite of all-cause mortality and rehospitalization for HF. Aldosterone concentrations in patients with and without events were 124.22 pmol L-1 (interquartile range (IQR): 48.62-256.20) and 96.33 pmol L-1 (IQR: 37.33-215.76), respectively (P=0.023). Aldosterone independently predicted all-cause mortality (adjusted hazard ratio (aHR), 1.55; 95% confidence interval (95%CI), 1.06-2.27; P=0.024) and the primary endpoint (aHR, 1.43; 95%CI, 1.11-1.85; P=0.006). Patients with high aldosterone concentrations were at higher risk of concentric remodeling (adjusted odds ratio (aOR), 1.45; 95% CI, 1.03-2.04; P=0.034). Patients with high aldosterone and B-type natriuretic peptide concentrations were at a higher risk of the primary endpoint (hazard ratio (HR), 1.85; 95%CI, 1.29-2.66; P=0.001). We conclude that elevated aldosterone is associated with a risk of rehospitalization with HF and all-cause mortality in patients with HFpEF.
Collapse
Affiliation(s)
- Bingbing Ke
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Xin Tan
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Lu Ren
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Yangkai Fan
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Yixin Zhang
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Fengjuan Li
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Qiqi Sun
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Tong Liu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Lixin Jia
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yuan Wang
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China.
| | - Jie Du
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China.
| |
Collapse
|
|
26
|
Shams E, Bonnice S, Mayrovitz HN. Diuretic Resistance Associated With Heart Failure. Cureus 2022; 14:e21369. [PMID: 35198282 PMCID: PMC8852330 DOI: 10.7759/cureus.21369] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 01/18/2022] [Indexed: 11/05/2022] Open
|
|
27
|
Biegus J, Nawrocka-Millward S, Zymliński R, Fudim M, Testani J, Marciniak D, Rosiek-Biegus M, Ponikowska B, Guzik M, Garus M, Ponikowski P. Distinct renin/aldosterone activity profiles correlate with renal function, natriuretic response, decongestive ability and prognosis in acute heart failure. Int J Cardiol 2021; 345:54-60. [PMID: 34728260 DOI: 10.1016/j.ijcard.2021.10.149] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/21/2021] [Accepted: 10/26/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Although renin-angiotensin-aldosterone system (RAAS) activation is believed to be the major driver of acute heart failure (AHF) episodes our understanding of its prevalence and clinical relevance in contemporary settings is incomplete. METHODS Serum renin and aldosterone were measured at day-1 and at discharge in patients (n = 211) that were hospitalized between 2016 and 2017 for AHF in a single cardiology center. The population was profiled based on upper limits of normal (ULN) of both biomarkers assessed at day-1 and linked with the clinical course and outcomes. RESULTS The study population constituted of three profiles: RAAS-/- (n = 121 [57%]); RAAS+/- (n = 60 [28%]); and RAAS+/+ (n = 30 [14%]). The RAAS+/+ profile had the lowest blood pressure and serum sodium at admission, day-2 and discharge compared to the other profiles (p < 0.001). The RAAS+/+ patients had significantly lower urine Na+ at admission (57.8 ± 36.7 vs 97.3 ± 31.3 and 86.4 ± 35.0), day-1 (52.7 ± 32.7 vs 85.3 ± 36.3 and 75.5 ± 33.9) mmol/l, vs RAAS-/- and RAAS+/- profiles, respectively, all p < 0.001. There was also a gradual decrease of renal function across increasing RAAS profiles. The RAAS+/+ profile received higher dose of furosemide at discharge 120 [80-160] vs the other profiles 80 [40-120] mg, p < 0.01. The risks of one year mortality or HF rehospitalization increased across the RAAS profiles (p < 0.001). The trajectory of renin or aldosterone change during hospitalization was not related to outcomes. CONCLUSIONS The RAAS overactivity is not essential for development of AHF. However, elevated RAAS is a marker of more advanced stages of heart failure, is related to low natriuresis and adverse clinical outcomes.
Collapse
Affiliation(s)
- Jan Biegus
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland; Institute of Heart Diseases, University Hospital, Wroclaw, Poland.
| | | | - Robert Zymliński
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland; Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Marat Fudim
- Division of Cardiology, Duke University Medical Center, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USA
| | | | - Dominik Marciniak
- Department of Drugs Form Technology, Faculty of Pharmacy, Medical University, Wroclaw, Poland
| | - Marta Rosiek-Biegus
- Department of Internal Medicine, Pneumology and Allergology, Medical University, Wroclaw, Poland
| | - Barbara Ponikowska
- Student Scientific Club, Department of Heart Diseases, Medical University, Wroclaw, Poland
| | - Mateusz Guzik
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Mateusz Garus
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland; Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| |
Collapse
|
|
28
|
Caton JB, Jimenez S, Wang SX. Things We Do for No Reason™: Fluid Restriction for the Management of Acute Decompensated Heart Failure in Patients With Reduced Ejection Fraction. J Hosp Med 2021; 16:754-756. [PMID: 34826269 DOI: 10.12788/jhm.3639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 04/14/2021] [Indexed: 11/20/2022]
Affiliation(s)
- Julia B Caton
- Division of Hospital Medicine, Department of Medicine, Stanford University Medical Center, Stanford, California
| | - Shirin Jimenez
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University Medical Center, Stanford, California
| | - Samantha Xy Wang
- Division of Hospital Medicine, Department of Medicine, Stanford University Medical Center, Stanford, California
| |
Collapse
|
|
29
|
Krim SR. Use of plasma renin and aldosterone profiles for prognostication in acute heart failure: A step forward but not ready for prime time. Int J Cardiol 2021; 348:111-112. [PMID: 34861322 DOI: 10.1016/j.ijcard.2021.11.062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 11/26/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Selim R Krim
- Section of Cardiomyopathy & Heart Transplantation, Division of Cardiology, John Ochsner Heart and Vascular Institute, Ochsner Clinic Foundation, New Orleans, USA; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, USA.
| |
Collapse
|
|
30
|
Inpatient Diuretic Management of Acute Heart Failure: A Practical Review. Am J Cardiovasc Drugs 2021; 21:595-608. [PMID: 33709346 DOI: 10.1007/s40256-020-00463-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/10/2020] [Indexed: 02/08/2023]
Abstract
The inpatient treatment of acute heart failure (AHF) is aimed at achieving euvolemia, relieving symptoms, and reducing rehospitalization. Adequate treatment of AHF is rooted in understanding the pharmacokinetics and pharmacodynamics of select diuretic agents used to achieve decongestion. While loop diuretics remain the primary treatment of AHF, the dosing strategies of loop diuretics and the use of adjunct diuretic classes to augment clinical response can be complex. This review examines the latest strategies for diuretic management in patients with AHF, including dosing and monitoring strategies, interaction of diuretics with other medication classes, use adjunctive therapies, and assessing endpoints for diuretic. The goal of the review is to guide the reader through commonly encountered clinical scenarios and pitfalls in the diuretic management of patients with AHF.
Collapse
|
|
31
|
Ivey-Miranda JB, Stewart B, Cox ZL, McCallum W, Maulion C, Gleason O, Meegan G, Amatruda JG, Moreno-Villagomez J, Mahoney D, Turner JM, Wilson FP, Estrella MM, Shlipak MG, Rao VS, Testani JM. FGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions. Circ Heart Fail 2021; 14:e008385. [PMID: 34689571 DOI: 10.1161/circheartfailure.121.008385] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contributor to adverse cardiorenal interactions such as sodium avidity, diuretic resistance, and neurohormonal activation, but this has not been conclusively demonstrated in humans. Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysfunction in humans with heart failure, independent of confounding factors. METHODS One hundred ninety-nine outpatients with heart failure undergoing diuretic treatment at the Yale Transitional Care Center were enrolled and underwent blood collection, and urine sampling before and after diuretics. RESULTS FGF-23 was associated with several metrics of disease severity such as higher home loop diuretic dose and NT-proBNP (N-terminal pro-B-type natriuretic peptide), and lower estimated glomerular filtration rate, serum chloride, and serum albumin. Multivariable analysis demonstrated no statistically significant association between FGF-23 and sodium avidity measured by fractional excretion of sodium, or proximal or distal tubular sodium reabsorption, either before diuretic administration or at peak diuresis (P≥0.11 for all). Likewise, FGF-23 was not independently associated with parameters of diuretic resistance (diuretic excretion, cumulative urine and sodium output, and loop diuretic efficiency [P≥0.33 for all]) or neurohormonal activation (plasma or urine renin [P≥0.36 for all]). Moreover, the upper boundary of the 95% CI of all the partial correlations were ≤0.30, supporting the lack of meaningful correlations. FGF-23 was not associated with mortality in multivariable analysis (P=0.44). CONCLUSIONS FGF-23 was not meaningfully associated with any cardiorenal parameter in patients with heart failure. While our methods cannot rule out a small effect, FGF-23 is unlikely to be a primary driver of cardiorenal interactions.
Collapse
Affiliation(s)
- Juan B Ivey-Miranda
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT.,Department of Heart Failure, Hospital de Cardiologia, Instituto Mexicano del Seguro Social, Mexico City (J.B.I.-M.)
| | - Brendan Stewart
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| | - Zachary L Cox
- Department of Pharmacy, Lipscomb University College of Pharmacy, Nashville, TN (Z.L.C.)
| | - Wendy McCallum
- Division of Nephrology, Tufts Medical Center, Boston, MA (W.M.)
| | - Christopher Maulion
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| | - Olyvia Gleason
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| | - Grace Meegan
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| | - Jonathan G Amatruda
- Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco (J.G.A., M.M.E., M.G.S.)
| | - Julieta Moreno-Villagomez
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT.,Neuroscience Project, Faculty of Higher Studies Iztacala, National Autonomous University of Mexico, Mexico City (J.M.-V.)
| | - Devin Mahoney
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| | - Jeffrey M Turner
- Department of Internal Medicine, Division of Nephrology (J.M.T.), Yale University School of Medicine, New Haven, CT
| | - F Perry Wilson
- Clinical and Translational Research Accelerator (F.P.W.), Yale University School of Medicine, New Haven, CT
| | - Michelle M Estrella
- Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco (J.G.A., M.M.E., M.G.S.)
| | - Michael G Shlipak
- Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco (J.G.A., M.M.E., M.G.S.)
| | - Veena S Rao
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| | - Jeffrey M Testani
- Department of Internal Medicine, Section of Cardiovascular Medicine (J.B.I.-M., B.S., C.M., O.G., G.M., J.M.-V., D.M., V.S.R., J.M.T.), Yale University School of Medicine, New Haven, CT
| |
Collapse
|
|
32
|
Chen Y, Zhou S, Zhang A, Huang J, Zhang G, Cui L. Temporal changes and prognostic value of plasma ghrelin level in patients with acute heart failure: a prospective study. Heart Vessels 2021; 37:419-425. [PMID: 34533592 DOI: 10.1007/s00380-021-01935-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 08/27/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Plasma ghrelin levels can be elevated in patients with acute heart failure (AHF). This study aimed to analyze the temporal changes and prognostic value of ghrelin levels in patients with AHF. METHODS This prospective study included patients with AHF at the Cardiology Department, Weifang People's Hospital (May 2018-October 2019), and age- and sex-matched healthy controls. Plasma ghrelin levels were measured. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate whether ghrelin levels could predict major cardiac adverse events (MACEs) during a 1-year follow-up. RESULTS Finally, 92 patients with AHF and 50 healthy controls were enrolled. Ghrelin levels were higher in patients with AHF at 1, 3, 12, and 24 h compared with controls (all P < 0.01). Ghrelin levels in the AHF group were higher at 3 and 12 h than at 1 and 24 h (P < 0.001). Ghrelin level at 3 h in patients with AHF was negatively correlated with the left ventricular end-diastolic diameter and left ventricular ejection fraction (both P < 0.05). MACEs occurred in 48 patients with AHF. Ghrelin levels were higher in the MACE group than in the non-MACE group at 1 (P = 0.011) and 3 h (P = 0.034). Multivariable regression showed that ghrelin level at 3 h was independently associated with MACEs [OR = 0.629, 95% confidence interval (CI): 0.515-0.742, P = 0.010], but the area under the ROC curve was only 0.629 (95% CI 0.515-0.742). CONCLUSIONS Plasma ghrelin levels are elevated in AHF and patients with MACEs during follow-up.
Collapse
Affiliation(s)
- Yanbo Chen
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.,Department of Cardioangiology, Weifang People's Hospital, Weifang, 261041, Shandong, China
| | - Sani Zhou
- Central Sterile Supply Department, Weifang People's Hospital, Weifang, 261041, Shandong, China
| | - Aiyuan Zhang
- Department of Cardioangiology, Weifang People's Hospital, Weifang, 261041, Shandong, China
| | - Jing Huang
- Department of Cardioangiology, Weifang People's Hospital, Weifang, 261041, Shandong, China
| | - Guangfang Zhang
- Department of Cardioangiology, Weifang People's Hospital, Weifang, 261041, Shandong, China
| | - Lianqun Cui
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
| |
Collapse
|
|
33
|
Kataoka H. Chloride in Heart Failure Syndrome: Its Pathophysiologic Role and Therapeutic Implication. Cardiol Ther 2021; 10:407-428. [PMID: 34398440 PMCID: PMC8555043 DOI: 10.1007/s40119-021-00238-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Indexed: 12/18/2022] Open
Abstract
Until recently, most studies of heart failure (HF) focused on body fluid dynamics through control of the sodium and water balance in the body. Chloride has remained largely ignored in the medical literature, and in clinical practice, chloride is generally considered as an afterthought to the better-known electrolytes of sodium and potassium. In recent years, however, the important role of chloride in the distribution of body fluid has emerged in the field of HF pathophysiology. Investigation of HF pathophysiology according to the dynamics of serum chloride is rational considering that chloride is an established key electrolyte for tubulo-glomerular feedback in the kidney and a possible regulatory electrolyte for body fluid distribution. The present review provides a historical overview of HF pathophysiology, followed by descriptions of the recent attention to the electrolyte chloride in the cardiovascular field, the known role of chloride in the human body, and recent new findings regarding the role of chloride leading to the proposed ‘chloride theory’ hypothesis in HF pathophysiology. Next, vascular and organ congestion in HF is discussed, and finally, a new classification and potential therapeutic strategy are proposed according to the ‘chloride theory’.
Collapse
|
|
34
|
Pulmonary Congestion Assessment in Heart Failure: Traditional and New Tools. Diagnostics (Basel) 2021; 11:diagnostics11081306. [PMID: 34441241 PMCID: PMC8394474 DOI: 10.3390/diagnostics11081306] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/16/2021] [Accepted: 07/18/2021] [Indexed: 12/28/2022] Open
Abstract
Congestion related to cardiac pressure and/or volume overload plays a central role in the pathophysiology, presentation, and prognosis of heart failure (HF). Most HF exacerbations are related to a progressive rise in cardiac filling pressures that precipitate pulmonary congestion and symptomatic decompensation. Furthermore, persistent symptoms and signs of congestion at discharge or among outpatients are strong predictors of an adverse outcome. Pulmonary congestion is also one of the most important diagnostic and therapeutic targets in chronic heart failure. The aim of this review is to analyze the importance of clinical, instrumental, and biochemical evaluation of congestion in HF by describing old and new tools. Lung ultrasonography (LUS) is an emerging method to assess pulmonary congestion. Accordingly, we describe the additive prognostic role of chest ultrasound with respect to traditional clinical and X-ray assessment in acute and chronic HF setting.
Collapse
|
|
35
|
Ong LT. Evidence based review of management of cardiorenal syndrome type 1. World J Methodol 2021; 11:187-198. [PMID: 34322368 PMCID: PMC8299910 DOI: 10.5662/wjm.v11.i4.187] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 05/09/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiorenal syndrome (CRS) type 1 is the development of acute kidney injury in patients with acute decompensated heart failure. CRS often results in prolonged hospitalization, a higher rate of rehospitalization, high morbidity, and high mortality. The pathophysiology of CRS is complex and involves hemodynamic changes, neurohormonal activation, hypothalamic-pituitary stress reaction, inflammation, and infection. However, there is limited evidence or guideline in managing CRS type 1, and the established therapeutic strategies mainly target the symptomatic relief of heart failure. This review will discuss the strategies in the management of CRS type 1. Six clinical studies have been included in this review that include different treatment strategies such as nesiritide, dopamine, levosimendan, tolvaptan, dobutamine, and ultrafiltration. Treatment strategies for CRS type 1 are derived based on the current literature. Early recognition and treatment of CRS can improve the outcomes of the patients significantly.
Collapse
Affiliation(s)
- Leong Tung Ong
- Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Wilayah Persekutuan Kuala Lumpur, Malaysia
| |
Collapse
|
|
36
|
AlHabeeb W, Hayajneh A. Continuation of Angiotensin Converting Enzyme Inhibitors in Acute Heart Failure. Int J Gen Med 2021; 14:2041-2045. [PMID: 34079343 PMCID: PMC8164353 DOI: 10.2147/ijgm.s310309] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/10/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose The aim of this study was to show whether blocking the deleterious effects of neurohormonal activation from furosemide by the use of ACEI/ARBs, or the improvement of renal perfusion by using these drugs allows better diuresis and renal function preservation. Patients and Methods This is a prospective, randomized study in which patients with chronic heart failure were included. Patients admitted for ACEI/ARBs maintenance with acute decompensated HF were added in the study. The patients were divided into two groups: group 1 had ACEI/ARBs continued during admission and group 2 had stopped taking them. Patients with acute heart failure were provided with angiotensin II receptor blockers. Therefore, the present study aims to differentiate between the uses of ACEI/ARBs blocking the deleterious effects of neurohormonal activation or the improvement of renal perfusion by holding these drugs to allow better diuresis and renal function preservation in a young population. Results The results showed that the mean age of 32 patients of group 1 was 58±15.3 and for group 2 56±15.6. On day of analysis, BP was 113/65±11.9/6.5 and 108/66.9±14.1/9.8, weight was 68.4±19.8 kg and 73.7±20.2 kg, net volume balance of urine output was 2810.3±1011.8 mL and 3941.7±2849.7 mL, and length of stay was 11.75±6 and 7.9±3.7 days for groups 1 and 2, respectively. There was no significant difference in SBP (p=0.2926), DBP (p=0.7369), weight (p=0.4798), glomerular filtration rate (GFR) (p=0.7), and volume balance (p=0.166). However, there was statistically significant difference in length of hospital stay (p=0.0392). Conclusion The study concluded that continuing ACEI/ARBs or holding them during IV diuresis had no difference in the effect on kidney function or diuresis. Length of stay appears to be shorter for those who held their ACEI/ARBs.
Collapse
Affiliation(s)
- Waleed AlHabeeb
- Cardiac Sciences Department, King Saud University, Riyadh, Saudi Arabia
| | - Ahmad Hayajneh
- King Fahad Cardiac Center, King Saud Saud University Medical City, Riyadh, Saudi Arabia
| |
Collapse
|
|
37
|
Wobbe B, Wagner J, Szabó DK, Rostás I, Farkas N, Garami A, Balaskó M, Hartmann P, Solymár M, Tenk J, Ottóffy M, Nagy A, Habon T, Hegyi P, Czopf L. Ultrafiltration is better than diuretic therapy for volume-overloaded acute heart failure patients: a meta-analysis. Heart Fail Rev 2021; 26:577-585. [PMID: 33244656 PMCID: PMC8024232 DOI: 10.1007/s10741-020-10057-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/16/2020] [Indexed: 11/23/2022]
Abstract
Studies on the effectiveness of ultrafiltration (UF) in patients hospitalized with acute decompensated heart failure (ADHF) have led to heterogeneous study outcomes. This meta-analysis aimed to assess the impact of UF therapy in ADHF patients. We searched the medical literature to identify well-designed studies comparing UF with the usual diuretic therapy in this setting. Systematic evaluation of 8 randomized controlled trials enrolling 801 participants showed greater fluid removal (difference in means 1372.5 mL, 95% CI 849.6 to 1895.4 mL; p < 0.001), weight loss (difference in means 1.592 kg, 95% CI 1.039 to 2.144 kg; p < 0.001) and lower incidences of worsening heart failure (OR 0.63, 95% CI 0.43 to 0.94, p = 0.022) and rehospitalization for heart failure (OR 0.54, 95% CI 0.36 to 0.82, p = 0.003) without a difference in renal impairment (OR 1.386, 95% CI 0.870 to 2.209; p = 0.169) or all-cause mortality (OR 1.13, 95% CI 0.75 to 1.71, p = 0.546). UF increases fluid removal and weight loss and reduces rehospitalization and the risk of worsening heart failure in congestive patients, suggesting ultrafiltration as a safe and effective treatment option for volume-overloaded heart failure patients.
Collapse
Affiliation(s)
- Bastian Wobbe
- Division of Cardiology, 1st Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Juliane Wagner
- Division of Cardiology, 1st Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Dorottya Kata Szabó
- Division of Cardiology, 1st Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Ildikó Rostás
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Nelli Farkas
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - András Garami
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Márta Balaskó
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Petra Hartmann
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Margit Solymár
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Judit Tenk
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Máté Ottóffy
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Arnold Nagy
- Department for Pediatrics, University of Pécs Medical School, Pécs, Hungary
| | - Tamás Habon
- Division of Cardiology, 1st Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - László Czopf
- Division of Cardiology, 1st Department of Medicine, University of Pécs Medical School, Pécs, Hungary.
- Division of Cardiology, 1st Department of Medicine, University of Pécs Medical School, Ifjúság u. 13., Pécs, H-7624, Hungary.
| |
Collapse
|
|
38
|
Abstract
Heart failure (HF) is one of the major causes of morbidity and mortality in the world. According to a 2019 American Heart Association report, about 6.2 million American adults had HF between 2013 and 2016, being responsible for almost 1 million admissions. As the population ages, the prevalence of HF is anticipated to increase, with 8 million Americans projected to have HF by 2030, posing a significant public health and financial burden. Acute decompensated HF (ADHF) is a syndrome characterized by volume overload and inadequate cardiac output associated with symptoms including some combination of exertional shortness of breath, orthopnea, paroxysmal nocturnal dyspnea (PND), fatigue, tissue congestion (e.g., peripheral edema) and decreased mentation. The pathology is characterized by hemodynamic abnormalities that result in autonomic imbalance with an increase in sympathetic activity, withdrawal of vagal activity and neurohormonal activation (NA) resulting in increased plasma volume in the setting of decreased sodium excretion, increased water retention and in turn an elevation of filling pressures. These neurohormonal changes are adaptive mechanisms which in the short term are associated with increased contractility of the left ventricular (LV) and improvement in cardiac output. But chronically, the failing heart is unable to overcome the excessive pressure and volume leading to worsening HF. The primary symptomatic management of ADHF includes intravenous (IV) diuresis to help with decongestion and return to euvolemic status. Even though diuretics have not been shown to provide any mortality benefit, they have been clinically proven to be of significant benefit in the acute decompensated phase, as well as in chronic management of HF. Loop diuretics remain the mainstay of therapy for symptomatic management of HF with use of thiazide diuretics for synergistic effect in the setting of diuretic resistance. Poor diuretic efficacy has been linked with higher mortality and increased rehospitalizations.
Collapse
Affiliation(s)
- Sarabjeet S Suri
- Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Salpy V Pamboukian
- Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL, USA
| |
Collapse
|
|
39
|
Narasimhan B, Aravinthkumar R, Correa A, Aronow WS. Pharmacotherapeutic principles of fluid management in heart failure. Expert Opin Pharmacother 2021; 22:595-610. [PMID: 33560159 DOI: 10.1080/14656566.2020.1850694] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Introduction: Heart failure is a major public health concern that is expected to increase over the decades to come. Despite significant advances, fluid overload and congestion remain a major therapeutic challenge. Vascular congestion and neurohormonal activation are intricately linked and the goal of therapy fundamentally aims to reduce both.Areas covered: The authors briefly review a number of core concepts that elucidate the link between fluid overload and neuro-hormonal activation. This is followed by a review of heart-kidney interactions and the impact of diuresis in this setting. Following an in-depth review of currently available pharmacological agents, the rationale and evidence behind their use, the authors end with a brief note on novel agents/approaches to aid volume management in HF.Expert opinion: A number of non-pharmacological advances in the management of volume overload in heart failure, though promising - are associated with a number of shortcomings. Pharmacological therapy remains the cornerstone of volume management. A number of novel approaches, utilizing existing therapies as well as the emergence of new agents over the past decade bode well for the vulnerable HF population.
Collapse
Affiliation(s)
- Bharat Narasimhan
- Department of Medicine, Mount Sinai Morningside, Mount Sinai West, New York, NY
| | | | - Ashish Correa
- Department of Cardiology, Mount Sinai Morningside, Mount Sinai West, Icahn School of Medicine at Mount Sinai
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical center/New York Medical College, Valhalla, NY
| |
Collapse
|
|
40
|
Kataoka H. Proposal for New Classification and Practical Use of Diuretics According to Their Effects on the Serum Chloride Concentration: Rationale Based on the "Chloride Theory". Cardiol Ther 2020; 9:227-244. [PMID: 32378135 PMCID: PMC7584720 DOI: 10.1007/s40119-020-00172-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Indexed: 02/06/2023] Open
Abstract
Currently, diuretic therapy for heart failure (HF) pathophysiology is primarily focused on the sodium and water balance. Over the last several years, however, chloride (Cl) has been recognized to have an important role in HF pathophysiology, as both a prognostic marker and a possible central factor regulating the body fluid status. I recently proposed a unifying hypothesis for HF pathophysiology, called the "chloride theory", during HF worsening and recovery, as follows. Chloride is the key electrolyte for regulating both reabsorption of tubular electrolytes and water in the kidney through the renin-angiotensin-aldosterone system and distributing body fluid in each compartment of the body. As changes between the serum Cl concentration and plasma volume are intimately associated with worsening HF and its recovery after decongestive therapy, modulation of the serum Cl concentration by careful selection and combination of various diuretics and their doses could become an attractive therapeutic option for HF. In this review, I will propose a new classification and practical use of diuretics according to their effects on the serum Cl concentration. Diuretic use according to this classification is expected to be a useful strategy for the treatment of patients with HF.
Collapse
|
|
41
|
Kristjánsdóttir I, Thorvaldsen T, Lund LH. Congestion and Diuretic Resistance in Acute or Worsening Heart Failure. Card Fail Rev 2020; 6:e25. [PMID: 33042585 PMCID: PMC7539143 DOI: 10.15420/cfr.2019.18] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 05/07/2020] [Indexed: 12/20/2022] Open
Abstract
Hospitalisation for acute heart failure (AHF) is associated with high mortality and high rehospitalisation rates. In the absence of evidence-based therapy, treatment is aimed at stabilisation and symptom relief. The majority of AHF patients have signs and symptoms of fluid overload, and, therefore, decongestion is the number one treatment goal. Diuretics are the cornerstone of therapy in AHF, but the treatment effect is challenged by diuretic resistance and poor diuretic response throughout the spectrum of chronic to worsening to acute to post-worsening HF. Adequate dosing and monitoring and evaluation of diuretic effect are important for treatment success. Residual congestion at discharge is a strong predictor of worse outcomes. Therefore, achieving euvolaemia is crucial despite transient worsening renal function.
Collapse
Affiliation(s)
- Ingibjörg Kristjánsdóttir
- Karolinska Institutet, Department of Medicine, Stockholm, Sweden; and Karolinska University Hospital, Heart and Vascular Theme Stockholm, Sweden
| | - Tonje Thorvaldsen
- Karolinska Institutet, Department of Medicine, Stockholm, Sweden; and Karolinska University Hospital, Heart and Vascular Theme Stockholm, Sweden
| | - Lars H Lund
- Karolinska Institutet, Department of Medicine, Stockholm, Sweden; and Karolinska University Hospital, Heart and Vascular Theme Stockholm, Sweden
| |
Collapse
|
|
42
|
Berger C, Prieur C, Bochaton T, Berthiller J, Luyt CE, Bonnefoy-Cudraz E. Patients with acute heart failure treated with the CARRESS-HF diuretic protocol in association with canrenoate potassium: Tolerance of high doses of canrenoate potassium. Arch Cardiovasc Dis 2020; 113:679-689. [PMID: 32948466 DOI: 10.1016/j.acvd.2020.05.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 03/13/2020] [Accepted: 05/12/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Oral mineralocorticoid receptor antagonists have failed to prove their efficacy for decongestion and potassium homeostasis in acute heart failure. Intravenous mineralocorticoid receptor antagonists have yet to be studied. AIM The aim of this study was to confirm the safety of high-dose potassium canrenoate in association with classic diuretics in acute heart failure. METHODS This retrospective single-centre study included consecutive patients who were hospitalized with acute heart failure between 2013 and 2018. One hundred patients with overload treated with the standardized diuretic protocol from the CARRESS-HF trial were included. There were no exclusion criteria relating to creatinine or kalaemia at the time of admission. Two groups were constituted on the basis of potassium canrenoate posology: a low-dose group (<300mg/day) and a high-dose group (≥300mg/day); the groups were similar in terms of baseline characteristics. RESULTS Mean daily potassium canrenoate doses were 198mg/day (range 100-280mg/day) in the low-dose group and 360mg/day (range 300-600mg/day) in the high-dose group. There was no significant difference between the high-dose and low-dose groups in terms of mortality, dialysis, renal function, hyperkalaemia, haemorrhage, sepsis or confusion. CONCLUSIONS Potassium canrenoate at high doses can be used safely in association with standard diuretics in acute heart failure, even in patients with altered renal function. A prospective study is required to evaluate the efficacy of high-dose potassium canrenoate in preventing hypokalaemia and improving decongestion.
Collapse
Affiliation(s)
- Clothilde Berger
- Unité de soins intensifs cardiologiques, Hôpital cardio-vasculaire Louis Pradel, groupement hospitalier Est, Hospices civils de Lyon, 28, avenue du Doyen-Lépine, 69677 Bron, France.
| | - Cyril Prieur
- Unité de soins intensifs cardiologiques, Hôpital cardio-vasculaire Louis Pradel, groupement hospitalier Est, Hospices civils de Lyon, 28, avenue du Doyen-Lépine, 69677 Bron, France
| | - Thomas Bochaton
- Unité de soins intensifs cardiologiques, Hôpital cardio-vasculaire Louis Pradel, groupement hospitalier Est, Hospices civils de Lyon, 28, avenue du Doyen-Lépine, 69677 Bron, France
| | - Julien Berthiller
- Service de Recherche et d'Épidémiologie Clinique, Pôle de santé publique des Hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France
| | - Charles-Edouard Luyt
- Réanimation médicale, Institut de cardiologie, Hôpital de la Pitié-Salpêtrière, AP-HP, 75013 Paris, France
| | - Eric Bonnefoy-Cudraz
- Unité de soins intensifs cardiologiques, Hôpital cardio-vasculaire Louis Pradel, groupement hospitalier Est, Hospices civils de Lyon, 28, avenue du Doyen-Lépine, 69677 Bron, France
| |
Collapse
|
|
43
|
Verbrugge FH, Guazzi M, Testani JM, Borlaug BA. Altered Hemodynamics and End-Organ Damage in Heart Failure: Impact on the Lung and Kidney. Circulation 2020; 142:998-1012. [PMID: 32897746 DOI: 10.1161/circulationaha.119.045409] [Citation(s) in RCA: 149] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures ("backward" failure), which may or may not coexist with reduced cardiac output ("forward" failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes.
Collapse
Affiliation(s)
- Frederik H Verbrugge
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (F.H.V., B.A.B.).,Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Belgium (F.H.V.)
| | - Marco Guazzi
- Cardiology University Department, Heart Failure Unit, University of Milano, IRCCS Policlinico San Donato, Milan, Italy (M.G.)
| | - Jeffrey M Testani
- Section of Cardiovascular Medicine, Yale University, New Haven, CT (J.M.T.)
| | - Barry A Borlaug
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (F.H.V., B.A.B.)
| |
Collapse
|
|
44
|
McNaughton CD, Collins SP, Testani JM. Accelerated decline in renal function after hospitalization for acute heart failure: an opportunity to intervene, or a sign of the inevitable? Eur J Heart Fail 2020; 22:1800-1802. [PMID: 32840958 DOI: 10.1002/ejhf.1992] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 08/21/2020] [Indexed: 11/10/2022] Open
Affiliation(s)
- Candace D McNaughton
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.,Geriatric Research and Education Clinical Center, Tennessee Valley Healthcare System VA Medical Center, Nashville, TN, USA
| | - Sean P Collins
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.,Geriatric Research and Education Clinical Center, Tennessee Valley Healthcare System VA Medical Center, Nashville, TN, USA
| | - Jeffrey M Testani
- Department of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
45
|
Morris AA, Nayak A, Ko YA, D'Souza M, Felker GM, Redfield MM, Tang WHW, Testani JM, Butler J. Racial Differences in Diuretic Efficiency, Plasma Renin, and Rehospitalization in Subjects With Acute Heart Failure. Circ Heart Fail 2020; 13:e006827. [PMID: 32635768 DOI: 10.1161/circheartfailure.119.006827] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Black patients have higher rates of hospitalization for acute heart failure than other race/ethnic groups. We sought to determine whether diuretic efficiency is associated with racial differences in risk for rehospitalization after acute heart failure. METHODS A post hoc analysis was performed on 721 subjects (age, 68±13 years; 22% black) enrolled in 3 acute heart failure clinical trials: ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure), DOSE-AHF (Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure), and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Repeated-measures ANOVA was used to test for a race×time effect on measures of decongestion. Diuretic efficiency was calculated as net fluid balance per total furosemide equivalents. In a subset of subjects, Cox regression was used to examine the association between race and rehospitalization according to plasma renin activity (PRA). RESULTS Compared with nonblack patients, black patients were younger and more likely to have nonischemic heart failure. During the first 72 to 96 hours, there was greater fluid loss (P=0.001), decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide; P=0.002), and lower levels of PRA (P<0.0001) in black patients. Diuretic efficiency was higher in black than in nonblack patients (403 [interquartile range, 221-795] versus 325 [interquartile range, 154-698]; P=0.014). However, adjustment for baseline PRA attenuated the association between black race and diuretic efficiency. Over a median follow-up of 68 (interquartile range, 56-177) days, there was an increased risk of all-cause and heart failure-specific rehospitalization in nonblack patients with increasing levels of PRA, while the risk of rehospitalization was relatively constant across levels of PRA in black patients. CONCLUSIONS Higher diuretic efficiency in black patients with acute heart failure may be related to racial differences in activity of the renin-angiotensin-aldosterone system.
Collapse
Affiliation(s)
- Alanna A Morris
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.A.M., A.N., M.D.)
| | - Aditi Nayak
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.A.M., A.N., M.D.)
| | - Yi-An Ko
- Department of Biostatistics and Bioinformatics, Emory Rollins School of Public Health, Atlanta, GA (Y.-A.K.)
| | - Melroy D'Souza
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA (A.A.M., A.N., M.D.)
| | | | | | | | - Jeffrey M Testani
- Division of Cardiology, Yale University School of Medicine, New Haven, CT (J.M.T.)
| | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson (J.B.)
| |
Collapse
|
|
46
|
Schaubroeck HA, Gevaert S, Bagshaw SM, Kellum JA, Hoste EA. Acute cardiorenal syndrome in acute heart failure: focus on renal replacement therapy. EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE 2020; 9:802-811. [PMID: 32597679 DOI: 10.1177/2048872620936371] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Almost half of hospitalised patients with acute heart failure develop acute cardiorenal syndrome. Treatment consists of optimisation of fluid status and haemodynamics, targeted therapy for the underlying cardiac disease, optimisation of heart failure treatment and preventive measures such as avoidance of nephrotoxic agents. Renal replacement therapy may be temporarily needed to support kidney function, mostly in case of diuretic resistant fluid overload or severe metabolic derangement. The best timing to initiate renal replacement therapy and the best modality in acute heart failure are still under debate. Several modalities are available such as intermittent and continuous renal replacement therapy as well as hybrid techniques, based on two main principles: haemofiltration and haemodialysis. Although continuous techniques have been associated with less haemodynamic instability and a greater chance of renal recovery, cohort data are conflicting and randomised controlled trials have not shown a difference in recovery or mortality. In the presence of diuretic resistance, isolated ultrafiltration with individualisation of ultrafiltration rates is a valid option for decongestion in acute heart failure patients. Practical tools to optimise the use of renal replacement therapy in acute heart failure-related acute cardiorenal syndrome were discussed.
Collapse
Affiliation(s)
| | - Sofie Gevaert
- Department of Cardiology, Ghent University Hospital, Belgium
| | - Sean M Bagshaw
- Department of Critical Care Medicine, University of Alberta, Canada
| | - John A Kellum
- Center for Critical Care Nephrology, University of Pittsburgh, USA
| | - Eric Aj Hoste
- Intensive Care Unit, Ghent University Hospital, Belgium.,Research Foundation-Flanders (FWO), Brussels, Belgium
| |
Collapse
|
|
47
|
Kobayashi M, Stienen S, Ter Maaten JM, Dickstein K, Samani NJ, Lang CC, Ng LL, Anker SD, Metra M, Preud'homme G, Duarte K, Lamiral Z, Girerd N, Rossignol P, van Veldhuisen DJ, Voors AA, Zannad F, Ferreira JP. Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure. ESC Heart Fail 2020; 7:953-963. [PMID: 32167681 PMCID: PMC7261568 DOI: 10.1002/ehf2.12634] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 11/26/2019] [Accepted: 01/14/2020] [Indexed: 12/17/2022] Open
Abstract
Aims Activation of the renin–angiotensin–aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF. Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT‐CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all‐cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT‐CHF study, median renin and aldosterone levels were 85.3 (percentile25–75 = 28–247) μIU/mL and 9.4 (percentile25–75 = 4.4–19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted‐HR (95% CI) = 1.47 (1.16–1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted‐HR (95% CI) = 1.16 (0.93–1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT‐CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies. Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the “point” measurement of renin and aldosterone in HF is of limited clinical utility.
Collapse
Affiliation(s)
- Masatake Kobayashi
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Susan Stienen
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Jozine M Ter Maaten
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Kenneth Dickstein
- Department of Internal Medicine, University of Bergen, Bergen, Norway.,Department of Cardiology, Stavanger University Hospital, Stavanger, Norway
| | - Nilesh J Samani
- Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Chim C Lang
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK
| | - Leong L Ng
- Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Stefan D Anker
- Department of Cardiology (CVK), Berlin, Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charité Universitätsmedizin Berlin Berlin, Germany
| | - Macro Metra
- Department of Cardiology, University and Civil hospitals of Brescia, Brescia, Italy
| | - Gregoire Preud'homme
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Kevin Duarte
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Zohra Lamiral
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Nicolas Girerd
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Patrick Rossignol
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Dirk J van Veldhuisen
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Adriaan A Voors
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Faiez Zannad
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - João Pedro Ferreira
- INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Université de Lorraine, Nancy, France
| |
Collapse
|
|
48
|
Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, Lerma EV, Mezue K, Molitch M, Mullens W, Ronco C, Tang WHW, McCullough PA. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation 2020; 139:e840-e878. [PMID: 30852913 DOI: 10.1161/cir.0000000000000664] [Citation(s) in RCA: 731] [Impact Index Per Article: 146.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future.
Collapse
|
|
49
|
Oliveros E, Oni ET, Shahzad A, Kluger AY, Lo KB, Rangaswami J, McCullough PA. Benefits and Risks of Continuing Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Mineralocorticoid Receptor Antagonists during Hospitalizations for Acute Heart Failure. Cardiorenal Med 2020; 10:69-84. [PMID: 32062648 DOI: 10.1159/000504167] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 10/12/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The renin-angiotensin-aldosterone axis plays a pivotal role in the pathophysiology of acute and chronic heart failure (HF) and represents an important target for guideline-directed medical therapy. SUMMARY The use of appropriate directed medical therapies for inhibition of the renin-angiotensin-aldosterone axis in chronic HF has been the subject of several landmark clinical trials, with high levels of adherence exhibited in the outpatient setting. However, less clarity exists with respect to the initiation, continuation, and cessation of renin-angiotensin-aldosterone system inhibitors (RAASi) in the setting of acute HF and exacerbation of HF necessitating hospitalization. In this review, we summarize relevant aspects of the physiology of the renin-angiotensin-aldosterone axis in acute HF and during decongestion. We also summarize the available evidence for the risks and benefits of initiating and continuing RAASi in acute HF. Key Message: We offer a decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome.
Collapse
Affiliation(s)
| | - Ebenezer T Oni
- Einstein Medical Center, Philadelphia, Pennsylvania, USA
| | - Anum Shahzad
- Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Aaron Y Kluger
- Baylor Heart and Vascular Institute, Dallas, Texas, USA.,Baylor Scott & White Research Institute, Dallas, Texas, USA
| | - Kevin Bryan Lo
- Einstein Medical Center, Philadelphia, Pennsylvania, USA
| | - Janani Rangaswami
- Einstein Medical Center, Philadelphia, Pennsylvania, USA.,Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Peter A McCullough
- Baylor Heart and Vascular Institute, Dallas, Texas, USA.,Baylor University Medical Center, Dallas, Texas, USA.,Baylor Heart and Vascular Hospital, Dallas, Texas, USA.,Texas A&M College of Medicine Health Science Center, Dallas, Texas, USA
| |
Collapse
|
|
50
|
McCallum W, Tighiouart H, Kiernan MS, Huggins GS, Sarnak MJ. Relation of Kidney Function Decline and NT-proBNP With Risk of Mortality and Readmission in Acute Decompensated Heart Failure. Am J Med 2020; 133:115-122.e2. [PMID: 31247182 PMCID: PMC7373496 DOI: 10.1016/j.amjmed.2019.05.047] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 05/21/2019] [Accepted: 05/23/2019] [Indexed: 01/17/2023]
Abstract
BACKGROUND Acute declines in kidney function occur in approximately 20%-30% of patients with acute decompensated heart failure, but its significance is unclear, and the importance of its context is not known. This study aimed to determine the prognostic value of a decline in kidney function in the context of decongestion among patients admitted with acute decompensated heart failure. METHODS Using data from patients enrolled in the Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome Study (CARRESS) and Diuretic Optimization Strategies Evaluation (DOSE) trials, we used multivariable Cox regression models to evaluate the association between decline in estimated glomerular filtration rate (eGFR) and change in N-terminal pro-b-type natriuretic peptide (NT-proBNP) with a composite outcome of death and rehospitalization, as well as testing for an interaction between the two. RESULTS Among 435 patients, in-hospital decline in eGFR was not significantly associated with death and rehospitalization (hazard ratio [HR] = 0.89 per 30% decline, 95% confidence interval [CI] 0.74, 1.07), whereas decline in NT-proBNP was associated with lower risk (HR = 0.69 per halving, 95% CI 0.58, 0.83). There was a significant interaction (P = 0.002 unadjusted; P = 0.03 adjusted) between decline in eGFR and change in NT-proBNP where a decline in eGFR was associated with better outcomes when NT-proBNP declined (HR = 0.78 per 30% decline in eGFR, 95% CI 0.61, 0.99), but not when NT-proBNP increased (HR = 0.99, 95% CI 0.76, 1.30). CONCLUSIONS Decline in kidney function during therapy for acute decompensated heart failure is associated with improved outcomes as long as NT-proBNP levels are decreasing as well, suggesting that incorporation of congestion biomarkers may aid clinical interpretation of eGFR declines.
Collapse
Affiliation(s)
- Wendy McCallum
- Division of Nephrology, Tufts Medical Center, Boston, Mass
| | - Hocine Tighiouart
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Mass; Tufts Clinical and Translational Science Institute, Tufts University, Boston, Mass
| | | | | | - Mark J Sarnak
- Division of Nephrology, Tufts Medical Center, Boston, Mass.
| |
Collapse
|