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Shouman WA, Najmeddine S, Sinno L, Dib Nehme R, Ghawi A, Ziade JA, Altara R, Amin G, Booz GW, Zouein FA. Hepatokines and their role in cardiohepatic interactions in heart failure. Eur J Pharmacol 2025; 992:177356. [PMID: 39922419 PMCID: PMC11862882 DOI: 10.1016/j.ejphar.2025.177356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/29/2025] [Accepted: 02/05/2025] [Indexed: 02/10/2025]
Abstract
Heart failure is one of the leading causes of death and disease worldwide. It is a condition that affects multiple systems within the body. There is a large body of evidence supporting that the liver is a major organ involved in the pathogenesis of heart failure. Cardiac hepatopathy and cirrhotic cardiomyopathy are two conditions that are associated with poor clinical outcomes in patients with heart failure. Despite the extensive proposed explanations of the mechanisms entailing heart failure, there remains a gap in the role of proteins and metabolic regulators produced by hepatocytes and their effect on the development, progression, and prognosis of heart failure, including adverse cardiac remodeling, fibrosis, cardiac cachexia, and renal dysfunction associated with heart failure. The aim of this review is to identify the major hepatokines being studied (adropin, fetuin-A, fetuin-B, FGF-21, selenoprotein P and α1-microglobulin) as modulators of metabolic homeostasis and cardiac dysfunction in heart failure. Research suggests that these factors play a role in modulating oxidative stress, fibrosis, apoptosis, inflammatory responses, immune cell activation, mitochondrial dysfunction, and cellular migration. The exact role of each of these hepatokines is under on-going research and requires more investigations for future clinical use.
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Affiliation(s)
- Wael A Shouman
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Sarah Najmeddine
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Lilas Sinno
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Ryan Dib Nehme
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Alaa Ghawi
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Joanna A Ziade
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
| | - Raffaele Altara
- Department of Pathology, School of Medicine, University of Mississippi Medical Center, 14, Jackson, MS, USA; Department of Anatomy & Embryology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Ghadir Amin
- Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - George W Booz
- Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Fouad A Zouein
- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon; The Cardiovascular, Renal, and Metabolic Diseases Research Center of Excellence, American University of Beirut Medical Center, Riad El-Solh, Beirut, Lebanon; Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
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Rankovic I, Babic I, Martinov Nestorov J, Bogdanovic J, Stojanovic M, Trifunovic J, Panic N, Bezmarevic M, Jevtovic J, Micic D, Dedovic V, Djuricic N, Pilipovic F, Curakova Ristovska E, Glisic T, Kostic S, Stojkovic N, Joksimovic N, Bascarevic M, Bozovic A, Elvin L, Onifade A, Siau K, Koriakovskaia E, Milivojevic V. Joint Group and Multi Institutional Position Opinion: Cirrhotic Cardiomyopathy-From Fundamentals to Applied Tactics. MEDICINA (KAUNAS, LITHUANIA) 2024; 61:46. [PMID: 39859028 PMCID: PMC11766788 DOI: 10.3390/medicina61010046] [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: 11/06/2024] [Revised: 12/20/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025]
Abstract
Cirrhotic cardiomyopathy (CCM) is a diagnostic entity defined as cardiac dysfunction (diastolic and/or systolic) in patients with liver cirrhosis, in the absence of overt cardiac disorder. Pathogenically, CCM stems from a combination of systemic and local hepatic factors that, through hemodynamic and neurohormonal changes, affect the balance of cardiac function and lead to its remodeling. Vascular changes in cirrhosis, mostly driven by portal hypertension, splanchnic vasodilatation, and increased cardiac output alongside maladaptively upregulated feedback systems, lead to fluid accumulation, venostasis, and cardiac dysfunction. Autocrine and endocrine proinflammatory cytokines (TNF-alpha, IL-6), as well as systemic endotoxemia stemming from impaired intestinal permeability, contribute to myocardial remodeling and fibrosis, which further compromise the contractility and relaxation of the heart. Additionally, relative adrenal insufficiency is often present in cirrhosis, further potentiating cardiac dysfunction, ultimately leading to the development of CCM. Considering its subclinical course, CCM diagnosis remains challenging. It relies mostly on stress echocardiography or advanced imaging techniques such as speckle-tracking echocardiography. Currently, there is no specific treatment for CCM, as it vastly overlaps with the treatment of heart failure. Diuretics play a central role. The role of non-selective beta-blockers in treating portal hypertension is established; however, their role in CCM remains somewhat controversial as their effect on prognosis is unclear. However, our group still advocates them as essential tools in optimizing the neurohumoral pathologic axis that perpetuates CCM. Other targeted therapies with direct anti-inflammatory and antioxidative effects still lack sufficient evidence for wide approval. This is not only a review but also a comprehensive distillation of the insights from practicing clinical hepatologists and other specialties engaged in advanced approaches to treating liver disease and its sequelae.
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Affiliation(s)
- Ivan Rankovic
- Gastroenterology and Liver Unit, Royal Cornwall Hospitals NHS Trust, London TR1 3LJ, UK (A.O.); (K.S.)
- Medical School, University of Exeter, Exeter TR10 9FE, UK
| | - Ivana Babic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.B.); (N.J.); (A.B.)
| | - Jelena Martinov Nestorov
- Clinic for Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.M.N.); (J.J.); (T.G.); (V.M.)
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
| | - Jelena Bogdanovic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.B.); (N.J.); (A.B.)
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
| | - Maja Stojanovic
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia;
| | - Jovanka Trifunovic
- Faculty of Dentistry Pancevo, University of Business Academy in Novi Sad, 21 000 Novi Sad, Serbia;
| | - Nikola Panic
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
- Center for Digestive Endoscopy, University Clinic “Dr Dragisa Misovic”, 11 000 Belgrade, Serbia
| | - Mihailo Bezmarevic
- Clinic for General Surgery, Military Medical Academy, Military Medical Academy Medical Faculty, University of Defense, 11 000 Belgrade, Serbia;
| | - Jelena Jevtovic
- Clinic for Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.M.N.); (J.J.); (T.G.); (V.M.)
| | - Dusan Micic
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
- Clinic for Emergency Surgery, Emergency Centre, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia
| | - Vladimir Dedovic
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
- Clinic for Cardiology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia;
| | - Nemanja Djuricic
- Clinic for Cardiology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia;
| | - Filip Pilipovic
- Institute for Orthopedic Surgery “Banjica”, 11 000 Belgrade, Serbia;
| | | | - Tijana Glisic
- Clinic for Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.M.N.); (J.J.); (T.G.); (V.M.)
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
| | - Sanja Kostic
- Clinic for Gynecology and Obstetrics, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia;
| | - Nemanja Stojkovic
- Department of Cardiology, University Clinic “Dr Dragisa Misovic”, 11 000 Belgrade, Serbia;
| | - Nata Joksimovic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.B.); (N.J.); (A.B.)
| | - Mileva Bascarevic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia;
| | - Aleksandra Bozovic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.B.); (N.J.); (A.B.)
| | - Lewis Elvin
- Gastroenterology and Liver Unit, Royal Cornwall Hospitals NHS Trust, London TR1 3LJ, UK (A.O.); (K.S.)
- Medical School, University of Exeter, Exeter TR10 9FE, UK
| | - Ajibola Onifade
- Gastroenterology and Liver Unit, Royal Cornwall Hospitals NHS Trust, London TR1 3LJ, UK (A.O.); (K.S.)
- Medical School, University of Exeter, Exeter TR10 9FE, UK
| | - Keith Siau
- Gastroenterology and Liver Unit, Royal Cornwall Hospitals NHS Trust, London TR1 3LJ, UK (A.O.); (K.S.)
- Medical School, University of Exeter, Exeter TR10 9FE, UK
| | - Elizaveta Koriakovskaia
- Department of Cardiology, Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia;
| | - Vladimir Milivojevic
- Clinic for Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11 000 Belgrade, Serbia; (J.M.N.); (J.J.); (T.G.); (V.M.)
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia; (M.S.); (N.P.); (D.M.)
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Sodoma AM, Pellegrini JR, Greenberg S, Sodoma A, Munshi R, Pellegrini RG, Singh J. Outcomes of Coronary Artery Bypass Grafting (CABG) Patients With and Without a History of Liver Transplant. Cureus 2024; 16:e75820. [PMID: 39822448 PMCID: PMC11737807 DOI: 10.7759/cureus.75820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Liver transplant (LT) patients face various challenges, including an increased risk of coronary artery disease (CAD) for a variety of reasons, with 70% of LT recipients having one cardiovascular event. Coronary artery bypass grafting (CABG) remains one of the most commonly performed major surgical procedures in the United States, with 20-30% of LT patients requiring a CABG. Many studies have analyzed when to perform a CABG and CAD workup pre-LT, but this population remains a problem. The patient population is challenging to study due to their rarity and complexity. Our study aimed to compile many patients through the National Inpatient Sample (NIS) database to gauge the outcomes of CABG in patients with and without a history of LT. Methods: Patients who underwent CABG with or without a history of LT were selected from the NIS from 2008 to 2020. The International Classification of Diseases (ICD) 9 and 10 codes were used to identify suitable records. Primary outcomes of interest were all-cause hospital mortality, shock, acute myocardial infarction, acute kidney injury (AKI), and a composite of these. Secondary outcomes included length of stay and total charges. Results: A weighted total of 2,407,349 CABG hospitalizations were included in this study. Of these, 1,833 had a history of LT. Overall, patients with a history of LT were more likely to be younger (65.16 vs. 66.16; p<0.001), male (81.6% vs. 73.66%; p<0.001), and more complex (Charlson Comorbidity Index (CCI) 5.89 vs. 4.16; p<0.001) than patients without a history of LT. Patients with a history of LT also had higher rates of diabetes mellitus type 2 (57.02% vs. 43.39%; p<0.001), end-stage renal disease (11.21% vs. 2.95%; p<0.001), and gastroesophageal reflux disease (GERD) (28.39% vs. 21.26%; p<0.001). CABG patients with a history of LT were less likely, however, to have hyperlipidemia (56.72% vs. 74.26%; p<0.001), hypertension (25.95% vs. 58.45%; p<0.001), obesity (19% vs. 23.42%; p=0.046), a history of smoking (12.06% vs. 18.66%; p<0.01), or alcohol use disorder (9.04% vs. 13.44%; p=0.017). We found that patients admitted for CABG with a history of LT had significantly higher adjusted odds of mortality (OR 1.84; p<0.01), AKI (OR 2.65; p<0.001), and composite outcome (OR 2.04; p<0.001). They also experienced a longer length of stay (1.7 days; p=0.02) and greater hospital charges ($26,761; p=0.029). CONCLUSION We found that CABG patients with a history of LT had nearly twofold higher odds of mortality, nearly threefold higher odds of AKI, and twofold higher odds of composite outcomes than CABG patients without LT. This corresponded to longer lengths of stay and increased hospital charges. Patients should require lower thresholds for left heart catheterization and more strict CAD testing before an LT due to the increased risk of adverse outcomes with the current standard of care.
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Affiliation(s)
- Andrej M Sodoma
- Internal Medicine, South Shore University Hospital, Bay Shore, USA
| | | | - Samuel Greenberg
- Anesthesia and Critical Care, Renaissance School of Medicine at Stony Brook University, Stony Brook, USA
| | - Andrej Sodoma
- Chemistry Faculty, College of Natural Sciences, Grand Canyon University, Phoenix, USA
| | - Rezwan Munshi
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
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Wang Z, Ban J, Zhou Y, Qie R. Causal association between gastrointestinal diseases and coronary artery disease: a bidirectional Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1458196. [PMID: 39473508 PMCID: PMC11518705 DOI: 10.3389/fendo.2024.1458196] [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: 07/02/2024] [Accepted: 09/26/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Coronary artery disease (CAD) has been a dominating reason of mortality globally due to its complexity of etiology. A variety of gastrointestinal disorders (GDs) have been accounted to be related to CAD. Thus, this study aims to determine their causal relationship by two-sample Mendelian randomization (MR) analysis. METHODS Single-nucleotide polymorphisms (SNPs) relevant to 22 GDs were employed as instrumental variables from the genome-wide association summary (GWAS) datasets. Genetic associations with CAD and HF were acquired from UK Biobank, FinnGen, and other GWAS studies. We conducted a univariable MR (UVMR) analysis followed by a meta-analysis. A multivariable MR (MVMR) analysis was then performed with smoking and body mass index (BMI) as justifications. Also, a bi-directional MR analysis was leveraged to verify the reverse causal correlations. RESULTS Generally, UVMR analyses separately observed the causal effects of GDs on CAD and HF. Genetic liability to gastroesophageal reflux disease displayed a positive association with both CAD (OR=1.19; 95%CI: 1.01-1.41) and HF (OR=1.22; 95%CI: 1.00-1.49) risk; genetic liability to celiac disease separately attributed to CAD (OR=1.02; 95%CI: 1.01-1.03) and HF (OR=1.01; 95%CI: 1.00-1.02), which also maintained after MVMR analysis. Besides, we observed mutually causal associations between CAD and celiac disease. CONCLUSION Our work suggested that genetic susceptibility to some GDs might causally increase the risk of CAD and HF, emphasizing the importance of preventing CAD in patients with GDs.
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Affiliation(s)
- Zhuoxi Wang
- First Clinical Medical School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Jifang Ban
- First Clinical Medical School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yabin Zhou
- Department of Cardiovascular, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Rui Qie
- Preventive Treatment Center, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
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Naimimohasses S, Keshavjee S, Wang B, Brudno M, Sidhu A, Bhat M. Proceedings of the 2024 Transplant AI Symposium. FRONTIERS IN TRANSPLANTATION 2024; 3:1399324. [PMID: 39319335 PMCID: PMC11421390 DOI: 10.3389/frtra.2024.1399324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 07/23/2024] [Indexed: 09/26/2024]
Abstract
With recent advancements in deep learning (DL) techniques, the use of artificial intelligence (AI) has become increasingly prevalent in all fields. Currently valued at 9.01 billion USD, it is a rapidly growing market, projected to increase by 40% per annum. There has been great interest in how AI could transform the practice of medicine, with the potential to improve all healthcare spheres from workflow management, accessibility, and cost efficiency to enhanced diagnostics with improved prognostic accuracy, allowing the practice of precision medicine. The applicability of AI is particularly promising for transplant medicine, in which it can help navigate the complex interplay of a myriad of variables and improve patient care. However, caution must be exercised when developing DL models, ensuring they are trained with large, reliable, and diverse datasets to minimize bias and increase generalizability. There must be transparency in the methodology and extensive validation of the model, including randomized controlled trials to demonstrate performance and cultivate trust among physicians and patients. Furthermore, there is a need to regulate this rapidly evolving field, with updated policies for the governance of AI-based technologies. Taking this in consideration, we summarize the latest transplant AI developments from the Ajmera Transplant Center's inaugural symposium.
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Affiliation(s)
- Sara Naimimohasses
- Division of Gastroenterology, Toronto General Hospital, Toronto, ON, Canada
- Ajmera Transplant Center, University Health Network, Toronto, ON, Canada
| | - Shaf Keshavjee
- Department of Innovation, University Health Network, Toronto, ON, Canada
| | - Bo Wang
- Department of Laboratory Medicine and Pathobiology, The Temerty Centre for AI Research and Education in Medicine, Toronto, ON, Canada
| | - Mike Brudno
- Department of Computer Science, University of Toronto, Toronto, ON, Canada
| | - Aman Sidhu
- Division of Gastroenterology, Toronto General Hospital, Toronto, ON, Canada
- Ajmera Transplant Center, University Health Network, Toronto, ON, Canada
| | - Mamatha Bhat
- Division of Gastroenterology, Toronto General Hospital, Toronto, ON, Canada
- Ajmera Transplant Center, University Health Network, Toronto, ON, Canada
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Boudabbous M, Hammemi R, Gdoura H, Chtourou L, Moalla M, Mnif L, Amouri A, Abid L, Tahri N. Cirrhotic cardiomyopathy: a subject that's always topical. Future Sci OA 2024; 10:FSO954. [PMID: 38817353 PMCID: PMC11137786 DOI: 10.2144/fsoa-2023-0110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 12/13/2023] [Indexed: 06/01/2024] Open
Abstract
Cirrhosis is the final stage in the development of hepatic fibrosis in chronic liver disease. It is associated with major hemodynamic disturbances defining the hyperdynamic circulation and may be complicated by specific cardiac involvement or cirrhotic cardiomyopathy which is a silent clinical condition that typically remains asymptomatic until the late stages of liver disease. Recently, new criteria defining CC, based on modern concepts and knowledge of heart failure, have been proposed. Despite knowledge of the main mechanisms behind this entity, there is no specific treatment available for cirrhotic cardiomyopathy. The management approach for symptomatic cardiomyopathy in cirrhotic patients is similar to that for left ventricular failure in non-cirrhotic individuals.
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Affiliation(s)
- Mona Boudabbous
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Rania Hammemi
- Cardiology, Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Hela Gdoura
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Lassad Chtourou
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Manel Moalla
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Leila Mnif
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Ali Amouri
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Leila Abid
- Cardiology, Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Nabil Tahri
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
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Müller M, Grasshoff C. [The Role of the Anaesthesiologist in Liver Transplantation - Preoperative Evaluation]. Anasthesiol Intensivmed Notfallmed Schmerzther 2024; 59:283-295. [PMID: 38759684 DOI: 10.1055/a-2152-7350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2024]
Abstract
Preoperative evaluation prior to listing for orthotopic liver transplantation (LT) requires a careful multidisciplinary approach with specialized teams including surgeons, hepatologists and anesthesiologists in order to improve short- and long-term clinical outcomes. Due to inadequate supply of donor organs and changing demographics, patients listed for LT have become older, sicker and share more comorbidities. As cardiovascular events are the leading cause for early mortality precise evaluation of risk factors is mandatory. This review focuses on the detection and management of coronary artery disease, cirrhotic cardiomyopathy, portopulmonary hypertension and hepatopulmonary syndrome in patients awaiting LT. Further insights are being given into scoring systems, patients with Acute-on-chronic-liver-failure (ACLF), frailty, NASH cirrhosis and into psychologic evaluation of patients with substance abuse.
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Xu H, Zhang Y, Gao Y. Prevalence and risk factors for cirrhotic cardiomyopathy: a prospective cross-sectional study. Eur J Gastroenterol Hepatol 2024; 36:469-475. [PMID: 38407871 DOI: 10.1097/meg.0000000000002716] [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: 02/27/2024]
Abstract
BACKGROUND This study aimed to assess cardiac structure and function in patients with cirrhosis, to investigate the prevalence of cirrhotic cardiomyopathy (CCM) in patients with cirrhosis of different etiologies and to analyze the risk factors for the development of CCM. METHODS This study selected cirrhotic patients aged 18-75 years who were hospitalized in Qilu Hospital of Shandong University. Patients with known heart disease, chronic lung disease, severe renal insufficiency, malignancy, thyroid disease, hypertension, diabetes or pregnancy were excluded. A total of 131 patients with cirrhosis were finally included. Based on the results of echocardiography, patients who met the diagnostic definition of CCM were included in the CCM group, otherwise, they were classified as the non-CCM group. The demographic and clinical data of the two groups were compared, and the clinical characteristics and risk factors of CCM were evaluated. RESULTS The overall prevalence of CCM was 24.4%, and the occurrence of CCM was not related to the etiology of liver cirrhosis. The prevalence of CCM was significantly higher among cirrhotic patients complicated with ascites (31.4% vs. 16.4%; P = 0.046) or with portal vein thrombosis (PVT) (42.9% vs. 17.1%; P = 0.003). Older age [odds ratio (OR) = 1.058; 95% confidence interval (CI), 1.005-1.113; P = 0.032] and PVT (OR = 2.999; 95% CI, 1.194-7.533; P = 0.019) were independent risk factors for the development of CCM. CONCLUSION The prevalence of CCM in cirrhotic patients was 24.4%, and the occurrence of CCM was not related to the etiology of cirrhosis. The prevalence of CCM was higher in cirrhotic patients with ascites or PVT. Older age and PVT are independent risk factors for CCM, but validation in larger sample studies is still needed.
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Affiliation(s)
| | - Yu Zhang
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
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Almeida F, Sousa A. Cirrhotic cardiomyopathy: Pathogenesis, clinical features, diagnosis, treatment and prognosis. Rev Port Cardiol 2024; 43:203-212. [PMID: 38142819 DOI: 10.1016/j.repc.2023.07.010] [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: 04/06/2023] [Revised: 06/09/2023] [Accepted: 07/30/2023] [Indexed: 12/26/2023] Open
Abstract
Cardiac dysfunction among cirrhotic patients has long been recognized in the medical community. While it was originally believed to be a direct result of alcohol toxicity, in the last 30 years cirrhotic cardiomyopathy (CCM) has been described as a syndrome characterized by chronic cardiac dysfunction in cirrhotic patients in the absence of known cardiac disease, regardless of the etiology of cirrhosis. CCM occurs in about 60% of patients with cirrhosis and plays a critical role in disease progression and treatment outcomes. Due to its predominantly asymptomatic course, diagnosing CCM is challenging and requires a high index of suspicion and a multiparametric approach. Patients with CCM usually present with the following triad: impaired myocardial contractile response to exercise, inadequate ventricular relaxation, and electrophysiological abnormalities (notably prolonged QT interval). In recent years, research in this area has grown expeditiously and a new set of diagnostic criteria has been developed by the Cirrhotic Cardiomyopathy Consortium, to properly identify patients with CCM. Nevertheless, CCM is still largely unknown among clinicians, and a major part of its pathophysiology and treatment is yet to be understood. In the present work, we aim to compile and summarize the available data on the pathogenesis, clinical features, diagnosis, treatment, and prognosis of CCM.
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Affiliation(s)
| | - Alexandra Sousa
- Cardiology Department, Unidade Local de Saúde de Entre o Douro e Vouga, Santa Maria da Feira, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS - Centre for Health Technology and Services Research, Porto, Portugal; RISE - Health Research Network, Porto, Portugal
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Siafarikas C, Kapelios CJ, Papatheodoridi M, Vlachogiannakos J, Tentolouris N, Papatheodoridis G. Sodium-glucose linked transporter 2 inhibitors in liver cirrhosis: Beyond their antidiabetic use. Liver Int 2024; 44:884-893. [PMID: 38293770 DOI: 10.1111/liv.15851] [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: 06/16/2023] [Revised: 01/02/2024] [Accepted: 01/15/2024] [Indexed: 02/01/2024]
Abstract
Type 2 diabetes mellitus (T2DM) and liver cirrhosis are clinical entities that frequently coexist, but glucose-lowering medication options are limited in cirrhotic patients. Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a class of glucose-lowering medication that act independently of insulin, by causing glycosuria in the proximal convoluted tubule. In this review, we aimed to briefly present the main data and to provide insight into the pathophysiology and potential usefulness of SGLT2 inhibitors in cirrhotic patients with or without T2DM. SGLT2 inhibitors have been proven useful as antidiabetic treatment in patients with metabolic liver disease, with most robust data from patients with metabolic dysfunction-associated steatotic liver disease (MASLD), where they also showed improvement in liver function parameters. Moreover, it has been suggested that SGLT2 inhibitors may have effects beyond their antidiabetic action. Accordingly, they have exhibited cardioprotective effects, expanding their indication in patients with heart failure without T2DM. Since decompensated liver cirrhosis and congestive heart failure share common pathophysiological features, namely renin-angiotensin-aldosterone axis and sympathetic nervous system activation as well as vasopressin secretion, SGLT2 inhibitors could also be beneficial in patients with decompensated cirrhosis, even in the absence of T2DM.
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Affiliation(s)
- Christos Siafarikas
- 1st Propaedeutic Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Chris J Kapelios
- Heart Failure and Heart Transplantation Unit, Onassis Cardiac Surgery Center, Athens, Greece
| | - Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Nikolaos Tentolouris
- 1st Propaedeutic Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
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11
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Burelle C, Clapatiuc V, Deschênes S, Cuillerier A, De Loof M, Higgins MÈ, Boël H, Daneault C, Chouinard B, Clavet MÉ, Tessier N, Croteau I, Chabot G, Martel C, Sirois MG, Lesage S, Burelle Y, Ruiz M. A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis. Commun Biol 2024; 7:356. [PMID: 38519536 PMCID: PMC10959946 DOI: 10.1038/s42003-024-06035-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 03/11/2024] [Indexed: 03/25/2024] Open
Abstract
Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity. Our results unveil a sex-dependent phenotypic remodeling beyond liver damage. Males, more than females, show fasting hypoglycemia and increased insulin sensitivity. They exhibit diastolic dysfunction, remodeling of the circulating lipoproteins and cardiac lipidome. Conversely, females do not manifest cardiac dysfunction but exhibit cardiometabolic impairments supported by impaired mitochondrial integrity and β-oxidation, remodeling of circulating lipoproteins and intracardiac accumulation of deleterious triglycerides. This study underscores metabolic defects in the liver resulting in significant sex-dependent cardiac abnormalities independent of obesity. This experimental model may prove useful to better understand the sex-related variability, notably in the heart, involved in the progression of lean-NAFLD.
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Affiliation(s)
- Charlotte Burelle
- Department of Medicine, Université de Montréal, Montreal, QC, Canada
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | - Valentin Clapatiuc
- Department of Medicine, Université de Montréal, Montreal, QC, Canada
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | - Sonia Deschênes
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | - Alexanne Cuillerier
- Faculty of Health Sciences and Medicine, University of Ottawa, Ottawa, OC, Canada
| | - Marine De Loof
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | | | - Hugues Boël
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | | | | | | | - Nolwenn Tessier
- Department of Medicine, Université de Montréal, Montreal, QC, Canada
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | | | - Geneviève Chabot
- Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada
| | - Catherine Martel
- Department of Medicine, Université de Montréal, Montreal, QC, Canada
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
| | - Martin G Sirois
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
- Department of Physiology and Pharmacology, Université de Montréal, Montreal, QC, Canada
| | - Sylvie Lesage
- Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada
| | - Yan Burelle
- Faculty of Health Sciences and Medicine, University of Ottawa, Ottawa, OC, Canada
| | - Matthieu Ruiz
- Research Center, Montreal Heart Institute, Montreal, QC, Canada.
- Department of Nutrition, Université de Montréal, Montreal, QC, Canada.
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12
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Dimitroglou Y, Aggeli C, Alexopoulou A, Tsartsalis D, Patsourakos D, Koukos M, Tousoulis D, Tsioufis K. The Contemporary Role of Speckle Tracking Echocardiography in Cirrhotic Cardiomyopathy. Life (Basel) 2024; 14:179. [PMID: 38398688 PMCID: PMC10890501 DOI: 10.3390/life14020179] [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: 12/18/2023] [Revised: 01/15/2024] [Accepted: 01/22/2024] [Indexed: 02/25/2024] Open
Abstract
Cirrhotic cardiomyopathy (CCM) is characterized by elevated cardiac output at rest, an inability to further increase contractility under stress, and diastolic dysfunction. The diagnosis of CCM is crucial as it can lead to complications during liver transplantation. However, its recognition poses challenges with conventional echocardiography techniques. Speckle tracking echocardiography (STE), particularly global longitudinal strain (GLS), is a novel index that enhances the diagnostic efficacy of echocardiography for both ischemic and non-ischemic cardiomyopathies. GLS proves more sensitive in identifying early systolic dysfunction and is also influenced by advanced diastolic dysfunction. Consequently, there is an expanding scope for GLS utilization in cirrhotic cases, with newly updated diagnostic criteria for CCM incorporating GLS. Specifically, systolic dysfunction is now defined as either a left ventricular ejection fraction below 50% or an absolute GLS below 18%. However, conflicting data on GLS alterations in liver cirrhosis patients persist, as many individuals with advanced disease and a poor prognosis exhibit a hyperdynamic state with preserved or increased GLS. Consequently, the presence of CCM, according to the updated criteria, does not exhibit a significant association-in the majority of studies-with the severity of liver disease and prognosis. Furthermore, information on other indices measured with STE, such as left atrial and right ventricular strain, is promising but currently limited. This review aims to offer a critical assessment of the existing evidence concerning the application of STE in patients with liver cirrhosis.
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Affiliation(s)
- Yannis Dimitroglou
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
| | - Constantina Aggeli
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
| | - Alexandra Alexopoulou
- Second Department of Medicine & Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece;
| | - Dimitrios Tsartsalis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
| | - Dimitrios Patsourakos
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
| | - Markos Koukos
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
| | - Dimitris Tousoulis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
| | - Konstantinos Tsioufis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece; (C.A.); (D.T.); (D.P.); (M.K.); (K.T.)
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13
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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14
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Groen RA, Ajmone Marsan N, Jukema JW, Coenraad MJ. Assessment of myocardial dysfunction in cirrhotic patients: Should we look at the left atrium rather than at the left ventricle? Liver Int 2023; 43:2586-2588. [PMID: 38011641 DOI: 10.1111/liv.15755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 09/21/2023] [Indexed: 11/29/2023]
Affiliation(s)
- Roos A Groen
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Nina Ajmone Marsan
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - J Wouter Jukema
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
- The Netherlands Heart Institute, Utrecht, The Netherlands
| | - Minneke J Coenraad
- Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands
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15
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Schneider H, Berliner D, Stockhoff L, Reincke M, Mauz JB, Meyer B, Bauersachs J, Wedemeyer H, Wacker F, Bettinger D, Hinrichs JB, Maasoumy B. Diastolic dysfunction is associated with cardiac decompensation after transjugular intrahepatic portosystemic shunt in patients with liver cirrhosis. United European Gastroenterol J 2023; 11:837-851. [PMID: 37897707 PMCID: PMC10637125 DOI: 10.1002/ueg2.12471] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 07/21/2023] [Indexed: 10/30/2023] Open
Abstract
BACKGROUND AND AIMS About 20% of patients develop cardiac decompensation within the first year after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for cardiac decompensation remain poorly defined. We aimed to evaluate predictors of cardiac decompensation after TIPS insertion in a large, well-defined cohort of patients with liver cirrhosis. METHODS 234 cirrhotic patients who received a TIPS at Hannover Medical School were retrospectively followed up for one year to assess the incidence of cardiac decompensation. Echocardiographic parameters and established diagnostic criteria for cardiac impairment (e.g. by the American Society of Echocardiography/ European Association of Cardiovascular Imaging (ASE/EACVI)) were investigated for an association with cardiac decompensation in a competing risk analysis. Survival was analyzed using a multivariable cox regression analysis adjusting for Freiburg index of post-TIPS survival. RESULTS Predominant TIPS indication was ascites (83%). Median age was 59 years, median MELD-score 12% and 58% were male. Overall, 41 patients (18%) developed cardiac decompensation within one year after TIPS insertion. Diastolic dysfunction according to the ASE/EACVI was diagnosed in 26% of patients at baseline and was linked to a significantly higher risk for cardiac decompensation (p = 0.025) after TIPS. When investigating individual echocardiographic baseline parameters, only pathological E/A (<0.8 or >2) was identified as a risk factor for cardiac decompensation (p = 0.015). Mortality and liver transplantation (n = 50) were significantly higher among patients who developed cardiac decompensation (HR = 5.29, p < 0.001) as well as in patients with a pathological E/A (HR = 2.34, p = 0.006). Cardiac high-risk status (44% of patients) was strongly linked to cardiac decompensation (HR = 2.93, p = 0.002) and mortality (HR = 2.24, p = 0.012). CONCLUSION Cardiac decompensation after TIPS is a frequent and important complication and is associated with reduced survival. American Society of Echocardiography/EACVI criteria and E/A seem to be the best parameters to predict the cardiac risk in cirrhotic patients undergoing TIPS insertion.
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Affiliation(s)
- Hannah Schneider
- Department of Gastroenterology, Hepatology, Infectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Dominik Berliner
- Department of Cardiology and AngiologyHannover Medical SchoolHannoverGermany
| | - Lena Stockhoff
- Department of Gastroenterology, Hepatology, Infectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Marlene Reincke
- Department of Medicine IIMedical Center University of FreiburgFreiburg im BreisgauGermany
| | - Jim B. Mauz
- Department of Gastroenterology, Hepatology, Infectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Bernhard Meyer
- Department of Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
| | - Johann Bauersachs
- Department of Cardiology and AngiologyHannover Medical SchoolHannoverGermany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Frank Wacker
- Department of Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
| | - Dominik Bettinger
- Department of Medicine IIMedical Center University of FreiburgFreiburg im BreisgauGermany
| | - Jan B. Hinrichs
- Department of Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and EndocrinologyHannover Medical SchoolHannoverGermany
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16
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Šimić S, Svaguša T, Grgurević I, Mustapić S, Žarak M, Prkačin I. Markers of cardiac injury in patients with liver cirrhosis. Croat Med J 2023; 64:362-373. [PMID: 37927191 PMCID: PMC10668036 DOI: 10.3325/cmj.2023.64.362] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 10/06/2023] [Indexed: 01/04/2025] Open
Abstract
Liver cirrhosis is an increasing public health problem and a major cause of morbidity and mortality. Accordingly, cirrhotic cardiomyopathy, a frequently underdiagnosed condition, is becoming a growing health problem. In the last 20 years, cardioselective biomarkers have been investigated for their diagnostic and prognostic properties for numerous conditions. The aim of this article is to review the literature on the relationship between the most commonly used cardioselective biomarkers (cardiac troponins I and T, N-terminal pro-B-type natriuretic peptide, brain natriuretic peptide, and heart-type fatty-acid binding protein) and the presence, functional stage, and clinical outcomes of liver cirrhosis. Elevated plasma levels of these biomarkers have been reported in patients with liver cirrhosis, and there is mounting evidence on their predictive value for clinical outcomes in this disease. In addition, elevated plasma levels of these biomarkers have been reported in patients before, during, and after liver transplantation, but in fewer studies. Due to their predictive value for clinical outcomes, we advocate the use of these markers in patients with liver cirrhosis and cirrhotic cardiomyopathy, as well as in candidates for liver transplant.
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Affiliation(s)
| | - Tomo Svaguša
- Tomo Svaguša, Department of Cardiovascular Disease, Dubrava University Hospital, Avenija Gojka Šuška 6, 10 000 Zagreb, Croatia,
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17
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Fatima I, Jahagirdar V, Kulkarni AV, Reddy R, Sharma M, Menon B, Reddy DN, Rao PN. Liver Transplantation: Protocol for Recipient Selection, Evaluation, and Assessment. J Clin Exp Hepatol 2023; 13:841-853. [PMID: 37693258 PMCID: PMC10483012 DOI: 10.1016/j.jceh.2023.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 04/13/2023] [Indexed: 09/12/2023] Open
Abstract
Liver transplantation (LT) is the definitive therapy for patients with end-stage liver disease, acute liver failure, acute-on-chronic liver failure, hepatocellular carcinoma, and metabolic liver diseases. The acceptance of LT in Asia has been gradually increasing and so is the expertise to perform LT. Preparing a patient with cirrhosis for LT is the most important aspect of a successful LT. The preparation for LT begins with the first index decompensation for a patient with cirrhosis. Patients planned for LT should undergo a thorough screening for infections, and a complete cardiac, pulmonology, and psychosocial evaluation pre-LT. In this review, we discuss the indications and contraindications of LT and the evaluation and assessment of patients with liver disease planned for LT.
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Affiliation(s)
- Ifrah Fatima
- University of Missouri-Kansas City School of Medicine, MO, USA
| | | | | | - Raghuram Reddy
- Department of Liver Transplantation Surgery, AIG Hospitals, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Balchandran Menon
- Department of Liver Transplantation Surgery, AIG Hospitals, Hyderabad, India
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18
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Perricone G, Artzner T, De Martin E, Jalan R, Wendon J, Carbone M. Intensive care management of acute-on-chronic liver failure. Intensive Care Med 2023; 49:903-921. [PMID: 37552333 DOI: 10.1007/s00134-023-07149-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/21/2023] [Indexed: 08/09/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome defined by an acute deterioration of the liver function associated with extrahepatic organ failures requiring intensive care support and associated with a high short-term mortality. ACLF has emerged as a major cause of mortality in patients with cirrhosis and chronic liver disease. ACLF has a unique pathophysiology in which systemic inflammation plays a key role; this provides the basis of novel therapies, several of which are now in clinical trials. Intensive care unit (ICU) therapy parallels that applied in the general ICU population in some organ failures but has peculiar differential characteristics in others. Critical care management strategies and the option of liver transplantation (LT) should be balanced with futility considerations in those with a poor prognosis. Nowadays, LT is the only life-saving treatment that can radically improve the long-term prognosis of patients with ACLF. This narrative review will provide insights on the current understanding of ACLF with emphasis on intensive care management.
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Affiliation(s)
- Giovanni Perricone
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy.
| | - Thierry Artzner
- Hôpitaux Universitaires de Strasbourg, 67000, Strasbourg, France
| | - Eleonora De Martin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Julia Wendon
- Liver Intensive Therapy Unit, Division of Inflammation Biology, King's College London, London, UK
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
- European Reference Network On Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
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19
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Jahangiri S, Abdiardekani A, Jamshidi S, Askarinejad A, Mosalamiaghili S, Bazrafshan M, Karimi M, Bazrafshan H, Bazrafshan drissi H. Electrocardiographic characteristics of cirrhotic patients and their association with Child-Pugh score. Clin Cardiol 2023; 46:967-972. [PMID: 37436825 PMCID: PMC10436787 DOI: 10.1002/clc.24089] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/30/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND Cardiac dysfunction is a serious complication of cirrhosis which is usually asymptomatic. We investigated the clinical and electrocardiographic (ECG)-related factors among patients with cirrhosis and our aim was to find any associations between ECG changes and the etiology of cirrhosis, as well as Child-Pugh score. HYPOTHESIS We hypothesized that some ECG-related factors, particularly prolonged QT interval, are more common in patients with cirrhosis. Also, these factors are associated with the severity of cirrhosis, measured by the Child-Pugh score. METHODS From April 2019 to December 2022, we reviewed admitted patients to Namazi and Abu-Ali Sina hospitals, Shiraz, Iran. Patients with confirmed diagnosis of cirrhosis and without concurrent disorders affecting the cardiovascular system were selected. Clinical and ECG-related data were then extracted for participants, and Child-Pugh score was calculated. RESULTS A total of 425 patients were included; the median age was 36 years, and 245 patients (57.6%) were men. Cryptogenic and primary sclerosing cholangitis were the most common etiologies. Prolonged QT followed by early transitional zone were the most common ECG changes (24.7% and 19.8%, respectively), which were significantly associated with the etiology of cirrhosis and Child-Pugh class. CONCLUSIONS Prolonged QT interval and presence of early transitional zone in patients with cirrhosis may indicate cardiac dysfunction, necessitating further evaluations.
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Affiliation(s)
- Soodeh Jahangiri
- Endocrine Research Center, Institute of Endocrinology and MetabolismIran University of Medical SciencesTehranIran
- Cardiovascular Research CenterShiraz University of Medical SciencesShirazIran
| | - Alireza Abdiardekani
- Cardiovascular Research CenterShiraz University of Medical SciencesShirazIran
- Department of Cardiology, Abu‐Ali Sina Charity HospitalShiraz University of Medical SciencesShirazIran
| | - Saideh Jamshidi
- Cardiovascular Research CenterShiraz University of Medical SciencesShirazIran
| | - Amir Askarinejad
- Rajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
| | | | - Mehdi Bazrafshan
- Cardiovascular Research CenterShiraz University of Medical SciencesShirazIran
| | - Mohamadreza Karimi
- Cardiovascular Research CenterShiraz University of Medical SciencesShirazIran
| | - Hanieh Bazrafshan
- Department of Neurology, Clinical Neurology Research CenterShiraz University of Medical SciencesShirazIran
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20
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Ohara H, Yoshihisa A, Ishibashi S, Matsuda M, Yamadera Y, Sugawara Y, Ichijo Y, Sato Y, Misaka T, Sato T, Oikawa M, Kobayashi A, Takeishi Y. Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure. J Am Heart Assoc 2023; 12:e029857. [PMID: 37301763 PMCID: PMC10356015 DOI: 10.1161/jaha.122.029857] [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: 02/21/2023] [Accepted: 05/05/2023] [Indexed: 06/12/2023]
Abstract
Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01-0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B-type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan-Meier analysis, cardiac event rate increased across increasing HVSI (log-rank, P=0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF and is associated with adverse prognosis in patients with HF.
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Affiliation(s)
- Himika Ohara
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Akiomi Yoshihisa
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
- Department of Clinical Laboratory SciencesFukushima Medical University School of Health ScienceFukushimaJapan
| | - Shinji Ishibashi
- Department of Clinical Laboratory MedicineFukushima Medical University HospitalFukushimaJapan
| | - Mitsuko Matsuda
- Department of Clinical Laboratory MedicineFukushima Medical University HospitalFukushimaJapan
| | - Yukio Yamadera
- Department of Clinical Laboratory MedicineFukushima Medical University HospitalFukushimaJapan
| | - Yukiko Sugawara
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Yasuhiro Ichijo
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Yu Sato
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Tomofumi Misaka
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Takamasa Sato
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Masayoshi Oikawa
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Atsushi Kobayashi
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
| | - Yasuchika Takeishi
- Department of Cardiovascular MedicineFukushima Medical University School of MedicineFukushimaJapan
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Virk MK, Mian MUM, Bashir DA, Wilkes JK, Schlingman T, Flores S, Kennedy C, Lam F, Arikan AA, Nguyen T, Mysore K, Galvan NTN, Coss-Bu J, Karpen SJ, Harpavat S, Desai MS. Elevated bile acids are associated with left ventricular structural changes in biliary atresia. Hepatol Commun 2023; 7:e0109. [PMID: 37058680 PMCID: PMC10109457 DOI: 10.1097/hc9.0000000000000109] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 02/09/2023] [Indexed: 04/16/2023] Open
Abstract
BACKGROUND In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood. METHODS Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A receiver-operating characteristic curve was generated to determine optimal threshold values of bile acids to detect pathologic changes in LV geometry using Youden index. Paraffin-embedded human heart tissue was separately analyzed by immunohistochemistry for the presence of bile acid-sensing Takeda G-protein-coupled membrane receptor type 5. RESULTS In the cohort, 52% (21/40) of children had abnormal LV geometry; the optimal bile acid concentration to detect this abnormality with 70% sensitivity and 64% specificity was 152 µmol/L (C-statistics=0.68). Children with bile acid concentrations >152 µmol/L had ∼8-fold increased odds of detecting abnormalities in LVM, LVM index, left atrial volume index, and LV internal diameter. Serum bile acids positively correlated with LVM, LVM index, and LV internal diameter. Separately, Takeda G-protein-coupled membrane receptor type 5 protein was detected in myocardial vasculature and cardiomyocytes on immunohistochemistry. CONCLUSION This association highlights the unique role of bile acids as one of the targetable potential triggers for myocardial structural changes in BA.
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Affiliation(s)
- Manpreet K. Virk
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | | | - Dalia A. Bashir
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - John K. Wilkes
- Pediatric Cardiology, Cook Children’s Medical Centre, Fort Worth, Texas, USA
| | - Tobias Schlingman
- Department of Pediatrics, Section of Pediatric Cardiology, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Saul Flores
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Curtis Kennedy
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Fong Lam
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Ayse A. Arikan
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
- Department of Pediatrics, Section of Nephrology, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Trung Nguyen
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Krupa Mysore
- Department of Pediatrics, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Nhu Thao Nguyen Galvan
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Jorge Coss-Bu
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
| | - Saul J. Karpen
- Department of Pediatric Gastroenterology and Hepatology, Emory School of Medicine, Atlanta, Georgia, USA
| | - Sanjiv Harpavat
- Department of Pediatrics, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Moreshwar S. Desai
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital Baylor College of Medicine, Houston, Texas, USA
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Chen YL, Zhao ZW, Li SM, Guo YZ. Value of red blood cell distribution width in prediction of diastolic dysfunction in cirrhotic cardiomyopathy. World J Gastroenterol 2023; 29:2322-2335. [PMID: 37124890 PMCID: PMC10134422 DOI: 10.3748/wjg.v29.i15.2322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/27/2023] [Accepted: 03/16/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Clinical diagnosis of cirrhotic cardiomyopathy (CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failure.
AIM To explore suitable biomarkers for early CCM prediction.
METHODS A total of 505 eligible patients were enrolled in this study and divided into four groups according to Child-Pugh classification: Group I, Class A without CCM (105 cases); Group II, Class A with CCM (175 cases); Group III, Class B with CCM (139 cases); and Group IV, Class C with CCM (86 cases). Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine whether red blood cell distribution width (RDW) was an independent risk factor for CCM risk. The relationships between RDW and Child-Pugh scores, Model for End-Stage Liver Disease (MELD) scores, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed by Pearson correlation analysis.
RESULTS A constant RDW increase was evident from Group I to Group IV (12.54 ± 0.85, 13.29 ± 1.19, 14.30 ± 1.96, and 16.25 ± 2.13, respectively). Pearson correlation analysis showed that RDW was positively correlated with Child-Pugh scores (r = 0.642, P < 0.001), MELD scores (r = 0.592, P < 0.001), and NT-proBNP (r = 0.715, P < 0.001). Furthermore, between Group I and Group II, RDW was the only significant index (odds ratio: 2.175, 95% confidence interval [CI]: 1.549-3.054, P < 0.001), and it reached statistical significance when examined by ROC curve analysis (area under the curve: 0.686, 95%CI: 0.624-0.748, P < 0.001).
CONCLUSION RDW can serve as an effective and accessible clinical indicator for the prediction of diastolic dysfunction in CCM, in which a numerical value of more than 13.05% may indicate an increasing CCM risk.
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Affiliation(s)
- Yan-Ling Chen
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Zi-Wen Zhao
- Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Shu-Mei Li
- Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Yong-Zhe Guo
- Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
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Tracy KM, Matsuoka LK, Alexopoulos SP. Update on combined heart and liver transplantation: evolving patient selection, improving outcomes, and outstanding questions. Curr Opin Organ Transplant 2023; 28:104-109. [PMID: 36454232 PMCID: PMC9994850 DOI: 10.1097/mot.0000000000001041] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
PURPOSE OF REVIEW Combined heart and liver transplantation (CHLT) is an uncommon but increasingly performed procedure with rising need as the population who has undergone Fontan palliation for single ventricle physiology grows. This article reviews the current literature to summarize what is known about patient selection and outcomes and highlights the questions that remain. RECENT FINDINGS Congenital heart disease (CHD) with Fontan-associated liver disease (FALD) has surpassed noncongenital heart disease as the most common indication for CHLT. In patients with failing Fontan physiology, accurate assessment of recoverability of liver injury remains challenging and requires multifaceted evaluation to determine who would benefit from isolated versus dual organ transplantation. Patient survival has improved over time without significant differences between those with and without a diagnosis of CHD. En bloc surgical technique and best use of intraoperative mechanical circulatory support are topics of interest as the field continues to evolve. SUMMARY A more refined understanding of appropriate patient selection and indication-specific outcomes will develop as we gain more experience with this complex operation and perform prospective, randomized studies.
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Affiliation(s)
- Kaitlyn M Tracy
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Cao Y, Zhang H, Li S, Li S, Sun S, Chen J, Ye T, Zhang X, Yuan J. Correlation analysis between myocardial work indices and liver function classification in patients with hepatitis B cirrhosis: A study with non-invasive left ventricular pressure-strain loop. Front Cardiovasc Med 2023; 10:1126590. [PMID: 36970359 PMCID: PMC10030708 DOI: 10.3389/fcvm.2023.1126590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 02/21/2023] [Indexed: 03/11/2023] Open
Abstract
BackgroundLiver cirrhosis is closely associated with cardiac dysfunction. The aims of this study were to evaluate left ventricular systolic function in patients with hepatitis B cirrhosis by non-invasive left ventricular pressure-strain loop (LVPSL) technique, and to explore the correlation between myocardial work indices and liver function classification.MethodsAccording to the Child-Pugh classification, 90 patients with hepatitis B cirrhosis were further divided into three groups: Child-Pugh A group (n = 32), Child-Pugh B group (n = 31), and Child-Pugh C group (n = 27). During the same period, 30 healthy volunteers were recruited as the control (CON) group. Myocardial work parameters, which included global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were derived from the LVPSL and compared among the four groups. The correlation between myocardial work parameters and Child-Pugh liver function classification was evaluated, and the independent risk factors affecting left ventricular myocardial work in patients with cirrhosis were investigated by univariable and multivariable linear regression analysis.ResultsGWI, GCW and GWE of Child-Pugh B and C groups were lower than those of CON group, while GWW was higher than that of CON group, and the changes were more obvious in Child-Pugh C group (P < 0.05). Correlation analysis revealed that GWI, GCW, and GWE were negatively correlated with liver function classification to various degrees (r = −0.54, −0.57, and −0.83, respectively, all P < 0.001), while GWW was positively correlated with liver function classification (r = 0.76, P < 0.001). Multivariable linear regression analysis showed that GWE was positively correlated with ALB (β = 0.17, P < 0.001), and negatively correlated with GLS (β = −0.24, P < 0.001).ConclusionsThe changes in the left ventricular systolic function in patients with hepatitis B cirrhosis were identified using non-invasive LVPSL technology, and myocardial work parameters are significantly correlated with liver function classification. This technique may provide a new method for the evaluation of cardiac function in patients with cirrhosis.
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Affiliation(s)
- Yang Cao
- Department of Ultrasound, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Huihui Zhang
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Shuai Li
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Siliang Li
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Shuowen Sun
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Jinwen Chen
- Department of Ultrasound, People’s Hospital of Henan University, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Ting Ye
- Department of Ultrasound, People’s Hospital of Henan University, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Xijun Zhang
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, China
- Correspondence: Xijun Zhang Jianjun Yuan
| | - Jianjun Yuan
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, China
- Correspondence: Xijun Zhang Jianjun Yuan
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Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review. Curr Probl Cardiol 2023; 48:101509. [PMID: 36402213 DOI: 10.1016/j.cpcardiol.2022.101509] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 11/11/2022] [Indexed: 11/18/2022]
Abstract
Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.
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Doycheva I, Izzy M, Watt KD. Cardiovascular assessment before liver transplantation. CARDIO-HEPATOLOGY 2023:309-326. [DOI: 10.1016/b978-0-12-817394-7.00005-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wang HY, Huang Y, Chen XZ, Zhang ZL, Gui C. Prognostic potential of liver injury in patients with dilated cardiomyopathy: a retrospective study. Eur J Med Res 2022; 27:237. [PMID: 36348400 PMCID: PMC9641949 DOI: 10.1186/s40001-022-00876-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/23/2022] [Indexed: 11/11/2022] Open
Abstract
Background Liver injury (LI) has been frequently observed in patients with dilated cardiomyopathy (DCM), whereas its prognostic value remains blurry. We attempted to appraise the prognostic effect of LI in patients with DCM. Methods This retrospective study included 523 patients with DCM. LI was defined as a threefold increase in aspartate transaminase (≥ 135 U/L) or alanine transaminase (≥ 180 U/L) or a twofold increase in total bilirubin (≥ 41 umol/L) during hospitalization. The population was segmented into non-liver injury (NLI) group and LI group based on liver function test data. To balance differences in covariates at baseline, 1:1 propensity score matching (PSM) was performed. Results Patients with LI had lower survival rate, compared with those with NLI (44.6% vs. 73.8%, P < 0.001). Similar results were also found in age (age > 50, 39.6% vs. 70.9%, P < 0.001; age ≤ 50, 51.3% vs. 79.5%, P < 0.001) and gender stratified analysis (male, 46.2% vs. 74.4%, P < 0.001; female 35.7% vs. 72.0%, P = 0.001). After PSM, the survival rate of patients with LI remained lower than those with NLI (44.6% vs. 64.1%, P = 0.019). Multivariable Cox regression analysis manifested that LI (hazard ratio [HR]: 1.692, 95% confidence interval [CI] 1.194–2.398, P = 0.003; HR: 1.675, 95% CI 1.078–2.604, P = 0.022, respectively) showed potent predictive effect on all-cause mortality in patients with DCM, both before and after PSM. Conclusions The occurrence of LI herald adverse outcomes in patients with DCM and attention to LI may be conducive to risk stratification and management. Supplementary Information The online version contains supplementary material available at 10.1186/s40001-022-00876-9.
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Impact of Cirrhotic Cardiomyopathy Diagnosed According to Different Criteria on Patients with Cirrhosis Awaiting Liver Transplantation: A Retrospective Cohort Study. Dig Dis Sci 2022; 67:5315-5326. [PMID: 35150344 DOI: 10.1007/s10620-022-07412-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 01/23/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Recently, the Cirrhotic Cardiomyopathy Consortium (Consortium) proposed criteria to replace the World Congress of Gastroenterology (WGO) criteria for cirrhotic cardiomyopathy (CCM) using contemporary echocardiography parameters. We assessed the impact of substituting WGO by Consortium criteria on the frequency of diagnosis and clinical outcomes in patients with cirrhosis awaiting liver transplantation (LT). METHODS Consecutive adults with cirrhosis approved for LT with echocardiography evaluation from January 2014 to December 2016 were screened. Patients with structural heart diseases were excluded. Two primary outcomes were: (1) frequency of CCM; (2) association of CCM with pre-transplant mortality. The secondary outcomes were pre-LT complications of acute kidney injury (AKI) and/or hepatic encephalopathy (HE), and post-LT mortality. RESULTS Of 386 patients screened, 278 were included. 238 (85.6%) and 208 (74.8%) patients met Consortium and WGO criteria, respectively; 180 (64.7%) patients fulfilled both the criteria, while 12 (4.3%) patients had no evidence of CCM by either criterion. Pre-LT mortality rates in Consortium-CCM group were similar to the other groups (19.3% vs 20.2% vs 25.0%). The patients with advanced diastolic dysfunction (DD) per Consortium-CCM criteria had higher mortality than the other groups. The rates of pre-LT AKI/HE rates and post-LT mortality were similar in Consortium-CCM and WGO-CCM groups. CONCLUSION The Consortium criteria do not impact the prevalence of CCM compared to WGO criteria and have similar predictive accuracy. Presence of advanced DD per the Consortium criteria increases the risk of pre-LT mortality and complications of AKI/HE. The patients with advanced DD could benefit from further monitoring and treatment.
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Abstract
AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.
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Affiliation(s)
- Giuseppe Cullaro
- Department of Medicine, University of California, San Francisco, California
| | - Swetha Rani Kanduri
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, The University of Queensland, Brisbane, Queensland, Australia
| | - Juan Carlos Q. Velez
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, The University of Queensland, Brisbane, Queensland, Australia
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Meucci MC, Hoogerduijn Strating MM, Butcher SC, van Rijswijk CSP, Van Hoek B, Delgado V, Bax JJ, Tushuizen ME, Marsan NA. Left atrial dysfunction is an independent predictor of mortality in patients with cirrhosis treated by transjugular intrahepatic portosystemic shunt. Hepatol Commun 2022; 6:3163-3174. [PMID: 36029167 PMCID: PMC9592786 DOI: 10.1002/hep4.2062] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 07/09/2022] [Accepted: 07/18/2022] [Indexed: 12/14/2022] Open
Abstract
The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long-term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two-dimensional speckle-tracking echocardiography (2D-STE). A total of 129 TIPS candidates (mean ± SD, 61 ± 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain ≤35%, based on a previously suggested cut-off value. The outcome was all-cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain ≤35%) was noted in 67 (52%) patients. After a median follow-up of 36 months (range, 12-80), 65 (50%) patients died. All-cause mortality rates increased along worse grades of LVDD (log-rank p = 0.007) and with LA dysfunction (log-rank p = 0.001). On multivariable Cox regression analysis, Model for End-Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all-cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta χ2 = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D-STE is independently associated with all-cause mortality in patients with cirrhosis treated by TIPS.
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Affiliation(s)
- Maria Chiara Meucci
- Department of CardiologyLeiden University Medical CenterLeidenthe Netherlands
- Department of Cardiovascular MedicineFondazione Policlinico Universitario A. Gemelli IRCSSRomeItaly
| | - Merte M. Hoogerduijn Strating
- Department of Gastroenterology and Hepatology, Transplantation CenterLeiden University Medical CenterLeidenthe Netherlands
| | - Steele C. Butcher
- Department of CardiologyLeiden University Medical CenterLeidenthe Netherlands
- Department of CardiologyRoyal Perth HospitalPerthAustralia
| | | | - Bart Van Hoek
- Department of Gastroenterology and Hepatology, Transplantation CenterLeiden University Medical CenterLeidenthe Netherlands
| | - Victoria Delgado
- Department of CardiologyLeiden University Medical CenterLeidenthe Netherlands
- Hospital University Germans Trias i Pujol, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i PujolBadalonaSpain
| | - Jeroen J. Bax
- Department of CardiologyLeiden University Medical CenterLeidenthe Netherlands
- Heart CenterUniversity of Turku and Turku University HospitalTurkuFinland
| | - Maarten E. Tushuizen
- Department of Gastroenterology and Hepatology, Transplantation CenterLeiden University Medical CenterLeidenthe Netherlands
| | - Nina Ajmone Marsan
- Department of CardiologyLeiden University Medical CenterLeidenthe Netherlands
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Prognostic implications of systolic function in patients with cirrhosis. GASTROENTEROLOGÍA Y HEPATOLOGÍA 2022; 46:446-454. [DOI: 10.1016/j.gastrohep.2022.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/15/2022] [Accepted: 10/10/2022] [Indexed: 11/09/2022]
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Kalluru R, Gadde S, Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP. Cirrhotic Cardiomyopathy: The Interplay Between Liver and Heart. Cureus 2022; 14:e27969. [PMID: 36120195 PMCID: PMC9467492 DOI: 10.7759/cureus.27969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2022] [Indexed: 11/05/2022] Open
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Nagraj S, Peppas S, Rubianes Guerrero MG, Kokkinidis DG, Contreras-Yametti FI, Murthy S, Jorde UP. Cardiac risk stratification of the liver transplant candidate: A comprehensive review. World J Transplant 2022; 12:142-156. [PMID: 36051452 PMCID: PMC9331410 DOI: 10.5500/wjt.v12.i7.142] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 06/15/2022] [Accepted: 06/27/2022] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular diseases (CVD) form a principal consideration in patients with end-stage liver disease (ESLD) undergoing evaluation for liver transplant (LT) with prognostic implications in the peri- and post-transplant periods. As the predominant etiology of ESLD continues to evolve, addressing CVD in these patients has become increasingly relevant. Likewise, as the number of LTs increase by the year, the proportion of older adults on the waiting list with competing comorbidities increase, and the demographics of LT candidates evolve with parallel increases in their CVD risk profiles. The primary goal of cardiac risk assessment is to preemptively reduce the risk of cardiovascular morbidity and mortality that may arise from hemodynamic stress in the peri- and post-transplant periods. The complex hemodynamics shared by ESLD patients in the pre-transplant period with adverse cardiovascular events occurring in only some of these recipients continue to challenge currently available guidelines and their uniform applicability. This review focusses on cardiac assessment of LT candidates in a stepwise manner with special emphasis on preoperative patient optimization. We hope that this will reinforce the importance of cardiovascular optimization prior to LT, prevent futile LT in those with advanced CVD beyond the stage of optimization, and thereby use the finite resources prudently.
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Affiliation(s)
- Sanjana Nagraj
- Department of Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, New York City, NY 10461, United States
| | - Spyros Peppas
- Department of Gastroenterology, Athens Naval Hospital, Athens 115 21, Greece
| | | | - Damianos G Kokkinidis
- Section of Cardiovascular Medicine, Yale University School of Medicine, Yale New Haven Hospital, New Haven, CT 06510, United States
| | | | - Sandhya Murthy
- Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY 10467, United States
| | - Ulrich P Jorde
- Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY 10467, United States
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Sudden death due to cirrhotic cardiomyopathy: An autopsy case report. J Forensic Leg Med 2022; 89:102369. [DOI: 10.1016/j.jflm.2022.102369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/03/2022] [Accepted: 05/04/2022] [Indexed: 11/21/2022]
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Han S, Park J, Hong SH, Park CS, Choi J, Chae MS. Cardiovascular manifestation of end-stage liver disease and perioperative echocardiography for liver transplantation: anesthesiologist’s view. Anesth Pain Med (Seoul) 2022; 17:132-144. [PMID: 35538654 PMCID: PMC9091670 DOI: 10.17085/apm.22132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 03/30/2022] [Indexed: 11/19/2022] Open
Abstract
Liver transplantation (LT) is the curative therapy for decompensated cirrhosis. However, anesthesiologists can find it challenging to manage patients undergoing LT due to the underlying pathologic conditions of patients with end-stage liver disease and the high invasiveness of the procedure, which is frequently accompanied by massive blood loss. Echocardiography is a non-invasive or semi-invasive imaging tool that provides real-time information about the structural and functional status of the heart and is considered to be able to improve outcomes by enabling accurate and detailed assessments. This article reviews the pathophysiologic changes of the heart accompanied by cirrhosis that mainly affect hemodynamics. We also present a comparative review of the diagnostic criteria for cirrhotic cardiomyopathy published by the World Congress of Gastroenterology in 2005 and the Cirrhotic Cardiomyopathy Consortium in 2019. This article discusses the conditions that could affect hemodynamic stability and postoperative outcomes, such as coronary artery disease, left ventricular outflow tract obstruction, portopulmonary hypertension, hepatopulmonary syndrome, pericardial effusion, cardiac tamponade, patent foramen ovale, and ascites. Finally, we cover a number of intraoperative factors that should be considered, including intraoperative blood loss, rapid reaccumulation of ascites, manipulation of the inferior vena cava, post-reperfusion syndrome, and adverse effects of excessive fluid infusion and transfusion. This article aimed to summarize the cardiovascular manifestations of cirrhosis that can affect hemodynamics and can be evaluated using perioperative echocardiography. We hope that this article will provide information about the hemodynamic characteristics of LT recipients and stimulate more active use of perioperative echocardiography.
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Affiliation(s)
- Sangbin Han
- Department of Emergency Medicine, Cheongyang Health Center County Hospital, Cheongyang, Korea
| | - Jaesik Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang Hyun Hong
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Soo Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jongho Choi
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min Suk Chae
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Corresponding author Min Suk Chae, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: 82-2-2258-6150 Fax: 82-2-537-1951 E-mail:
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Kim SH, Lee JG, Ju HM, Choi S, Yang H, Koo BN. Propofol prevents further prolongation of QT interval during liver transplantation. Sci Rep 2022; 12:4636. [PMID: 35301381 PMCID: PMC8931121 DOI: 10.1038/s41598-022-08592-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 02/28/2022] [Indexed: 11/21/2022] Open
Abstract
Here, we aimed to compare the effects of two anesthetic methods (desflurane inhalation anesthesia vs. propofol-based total intravenous anesthesia (TIVA)] on corrected QT interval (QTc) values during living donor liver transplantation. Altogether, 120 patients who underwent living donor liver transplantation were randomized to either the desflurane or TIVA group. The primary outcome was intraoperative QTc change. Other electrocardiogram, hemodynamic findings and postoperative outcomes were examined as secondary outcomes. QTc values were prolonged intraoperatively in both groups; however, the change was smaller in the TIVA group than in the desflurane group (PGroup × Time < 0.001). More patients had QTc values of > 500 ms in the desflurane group than in the TIVA group (63.3% vs. 28.3%, P < 0.001). In patients with preoperative QTc prolongation, QTc was further prolonged in the desflurane group, but not in the TIVA group (PGroup × Time < 0.001). Intraoperative norepinephrine and vasopressin use were higher in the desflurane group than in the TIVA group. Propofol-based TIVA may reduce QTc prolongation during living donor liver transplantation compared to that observed with desflurane inhalational anesthesia, particularly in patients with preoperative QTc prolongation. Additionally, patients managed with propofol-based TIVA required less vasopressor during the procedure as compared with those managed with desflurane inhalational anesthesia.
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Affiliation(s)
- Seung Hyun Kim
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyang Mi Ju
- Department of Anesthesiology and Pain Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - SuYoun Choi
- Department of Anesthesiology and Pain Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyukjin Yang
- Department of Anesthesiology and Pain Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Bon-Nyeo Koo
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
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Akhtar S. Preoperative evaluation of geriatric patients undergoing liver transplantation. Curr Opin Anaesthesiol 2022; 35:96-104. [PMID: 34878418 DOI: 10.1097/aco.0000000000001084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW As the population of the world is aging the number of geriatric patients undergoing liver transplantation (LT) is also increasing. They pose a unique challenge for the caregivers, as they have age-related physiological changes, multiple comorbidities and cirrhosis-related pathologies. RECENT FINDINGS Twenty-two percent of patients who undergo LT are older than 65 years. Many patients suffer from nonalcoholic steatohepatitis (NASH), hepatocellular carcinoma and hepatitis-C virus. Incidence of NASH tends to increase with age, obesity, diabetes and metabolic syndrome. Elderly patients require comprehensive cognitive, cardiac and pulmonary evaluation prior to LT. Cirrhotic cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension and frailty are of specific concern. SUMMARY Proportion of elderly patients who are undergoing LT continues to increase. These patients require comprehensive cardiopulmonary and frailty evaluation. Consensus-based practice advisories need to be developed to standardize preoperative evaluation of geriatric patients awaiting LT.
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Affiliation(s)
- Shamsuddin Akhtar
- Department of Anesthesiology and Pharmacology, Yale School of Medicine, New Haven, Connecticut, USA
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Anikhindi SA, Ranjan P, Kumar M, Mohan R. A Prospective Study of Prevalence and Predictors of Cirrhotic Cardiomyopathy and Its Role in Development of Hepatorenal Syndrome. J Clin Exp Hepatol 2022; 12:853-860. [PMID: 35677509 PMCID: PMC9168708 DOI: 10.1016/j.jceh.2021.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Cirrhotic cardiomyopathy (CCM) is a term used to collectively describe abnormal structural and functional changes in heart of patients with cirrhosis. The present study was undertaken to find the prevalence of CCM in patients with liver cirrhosis and its predictors. We also followed these patients to evaluate the role of CCM in the development of hepatorenal syndrome (HRS). MATERIALS & METHODS This was a prospective study carried out in department of Gastroenterology, Sir Ganga Ram hospital, New Delhi. A total of 104 patients with liver cirrhosis were included. Liver cirrhosis was diagnosed on basis of clinical, biochemical, and imaging features. CCM was defined based on echocardiography. Dobutamine stress echocardiography and hepatic venous pressure gradient (HVPG) were performed in patients who gave consent. HRS was defined as per standard criteria. Patients with CCM were followed for development of HRS. RESULTS Fifty (48%) patients were diagnosed with CCM. All patients had diastolic dysfunction, and none had systolic dysfunction. Median age of patients with CCM was significantly higher (59 [31-78 y] vs. 52 [24-70 y], P < 0.05). Severity of liver disease (Child Turcotte Pugh score and model for end-stage liver disease score) and portal pressures (HVPG) did not differ in patients with or without CCM. Patients with CCM did not have increased incidence of HRS at the end of 6-month follow-up study. CONCLUSION The presence of CCM was not related with the severity of liver dysfunction or portal pressures. Age was a significant determinant of CCM. Diastolic cardiac dysfunction does not influence the occurrence of HRS.
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Key Words
- 2D echo, two-dimensional echocardiography
- CCM, cirrhotic cardiomyopathy
- CTP, Child Turcotte Pugh
- DD, diastolic dysfunction
- DSE, dobutamine stress echocardiography
- FHVP, free hepatic venous pressure
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- LVEF, left ventricular ejection fraction
- MELD, model for end-stage liver disease
- TDI, tissue Doppler imaging
- cardiomyopathy
- cirrhosis
- diastolic cardiac dysfunction
- hepatorenal syndrome
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Affiliation(s)
- Shrihari A. Anikhindi
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Piyush Ranjan
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India,Address for correspondence: Piyush Ranjan, Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, 110 060, New Delhi, India.
| | - Mandhir Kumar
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Rajat Mohan
- Department of Cardiology, Sir Ganga Ram Hospital, New Delhi, India
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Bhangui P, Bhangui P, Aneja M, Sharma N, Gupta N, Soin A, Vohra V. Living Donor Liver Transplantation in a Cohort of Recipients With Left Ventricular Systolic Dysfunction. J Clin Exp Hepatol 2022; 12:1040-1047. [PMID: 35814511 PMCID: PMC9257861 DOI: 10.1016/j.jceh.2022.03.001] [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: 01/09/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Data on feasibility, management, and outcomes of liver transplantation (LT) in patients with pre-existing left ventricular systolic dysfunction (LVSD), severe coronary artery disease (CAD) or cirrhotic cardiomyopathy (CCM) is scarce. METHODS We reviewed outcomes of living donor liver transplantation (LDLT) in recipients with LVSD (ejection fraction [EF] < 50%) from our series of 1946 LDLT's performed between July 2010 and July 2018. RESULTS LVSD was detected in 12 male patients with a mean age, BMI and MELD of 52 ± 9 years, 25 ± 5 kg/m2, and 19 ± 4 respectively. Out of these, 6 patients had CAD (2 with previous coronary artery bypass graft, 1 following recent percutaneous transluminal coronary angioplasty, 2 post myocardial infarction, 1 noncritical CAD), and 6 had CCM. The EF ranged from 25% to 45%. Ethanol was the predominant underlying etiology for cirrhosis (50%). During LDLT, 2 patients developed ventricular ectopic rhythm and were managed successfully with intravenous lidocaine. Stress cardiomyopathy manifested in 3 patients post operatively with decreased EF, of which 2 improved, while 1 needed IABP support and succumbed to multiorgan failure on 8th postoperative day (POD). Another patient died on POD30 due to septic shock. Both these patients had higher MELD scores (actual MELD), extremes of BMI (17.3and 35.8 kg/m2) and were diabetic. There were no long-term cardiac deaths. The 1-year, and 5-year survival were 75%, and 66%, respectively. CONCLUSION Among potential LT recipients with LVSD, those with stable CAD and good performance status, and well optimized CCM patients may be considered for LDLT after careful risk stratification in experienced centers.
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Key Words
- CABG, Coronary artery bypass graft
- CAC, coronary artery calcium score
- CAD, coronary artery disease
- CCM, cirrhotic cardiomyopathy
- CLD, chronic liver disease
- CTP, Child Turcotte Pugh
- DDLT, Deceased donor liver transplantation
- DSE, dobutamine stress echo
- ECG, electrocardiogram
- EF, ejection fraction
- ESLD, end stage liver disease
- GRWR, Graft to recipient weight ratio
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus
- IABP, intra-aortic balloon pump
- ICU, intensive care unit
- LDLT outcomes
- LDLT, Living donor liver transplantation
- LT, Liver transplantation
- LVSD, left ventricular systolic dysfunction
- MELD, Model for End Stage Liver Disease
- METS score, metabolic equivalents score
- NAFLD, nonalcoholic fatty liver disease
- OS, Overall survival
- PAC, pulmonary artery catheter
- PHT, portal hypertension
- PTCA, percutaneous transluminal coronary angioplasty
- TEE, transesophageal echocardiography
- cardiac complications
- cardiac evaluation
- cirrhotic cardiomyopathy
- coronary artery disease
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Affiliation(s)
- Pooja Bhangui
- Department of Liver Transplant and GI Anesthesia, Medanta-The Medicity, Gurgaon, Haryana, India
- Address for correspondence: Pooja Bhangui, Department of Liver Transplant and GI Anesthesia, Medanta-The Medicity, Gurugram, Delhi, 122001, NCR, India.
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi, NCR, India
| | - Manish Aneja
- Department of Liver Transplant and GI Anesthesia, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Nishant Sharma
- Department of Liver Transplant and GI Anesthesia, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Nikunj Gupta
- Department of Liver Transplant and GI Anesthesia, Medanta-The Medicity, Gurgaon, Haryana, India
| | - A.S. Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi, NCR, India
| | - Vijay Vohra
- Department of Liver Transplant and GI Anesthesia, Medanta-The Medicity, Gurgaon, Haryana, India
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Liu SH, Lo LW, Chou YH, Lin WL, Tsai TY, Cheng WH, Lin YJ, Chang SL, Hu YF, Chung FP, Huang HC, Chen SA. Evidence of Ventricular Arrhythmogenicity and Cardiac Sympathetic Hyperinnervation in Early Cirrhotic Cardiomyopathy. Front Physiol 2021; 12:719883. [PMID: 34955871 PMCID: PMC8692789 DOI: 10.3389/fphys.2021.719883] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 11/03/2021] [Indexed: 12/29/2022] Open
Abstract
Cirrhotic cardiomyopathy (CMP) is associated with altered cardiac electrophysiological (EP) properties, which leads to the risk of ventricular arrhythmias (VAs). We aimed to evaluate the EP properties, autonomic, and structural remodeling in a rabbit model with early liver cirrhosis (LC). Twelve rabbits were assigned to the sham and LC groups. The early-stage LC was induced by the ligation of the common bile duct. All rabbits received an EP study, VA inducibility test, myocardial, and liver histology staining. Western blot analyses of protein expression and tyrosine hydroxylase stain for sympathetic nerves were performed. The effective refractory period the LC group was significantly longer than the sham group [i.e., left ventricle (LV) 205.56 ± 40.30 vs. 131.36 ± 7.94 ms; right ventricle (RV) 206.78 ± 33.07 vs. 136.79 ± 15.15 ms; left atrium (LA) 140.56 ± 28.75 vs. 67.71 ± 14.29 ms; and right atrium (RA) 133.78 ± 40.58 vs. 65.43 ± 19.49 ms, all p < 0.01], respectively. The VA inducibility was elevated in the LC group when compared with the sham group (i.e., 21.53 ± 7.71 vs. 7.76 ± 2.44%, p = 0.013). Sympathetic innervation (102/μm2/mm2) was increased in all cardiac chambers of the LC group compared with the sham group (i.e., LV 9.11 ± 4.86 vs. 0.17 ± 0.15, p < 0.01; RV 4.36 ± 4.95 vs. 0.18 ± 0.12, p = 0.026; LA 6.79 ± 1.02 vs. 0.44 ± 0.20, p = 0.018; and RA 15.18 ± 5.12 vs. 0.10 ± 0.07, p = 0.014), respectively. Early LC is presented with an increased ventricular vulnerability, structural heterogeneity, and sympathetic innervation. Close monitoring for fatal arrhythmias is warranted in patients with early stages of LC.
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Affiliation(s)
- Shin-Huei Liu
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Li-Wei Lo
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Hui Chou
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Lun Lin
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tsung-Ying Tsai
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wen-Han Cheng
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yenn-Jiang Lin
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shih-Lin Chang
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Feng Hu
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Fa-Po Chung
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hui-Chun Huang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shih-Ann Chen
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan
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What's New in Cirrhotic Cardiomyopathy?-Review Article. J Pers Med 2021; 11:jpm11121285. [PMID: 34945757 PMCID: PMC8705028 DOI: 10.3390/jpm11121285] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/21/2021] [Accepted: 11/25/2021] [Indexed: 01/16/2023] Open
Abstract
Cirrhotic cardiomyopathy (CCM) is a relatively new medical term. The constant development of novel diagnostic and clinical tools continuously delivers new data and findings about this broad disorder. The purpose of this review is to summarize current facts about CCM, identify gaps of knowledge, and indicate the direction in which to prepare an updated definition of CCM. We performed a review of the literature using scientific data sources with an emphasis on the latest findings. CCM is a clinical manifestation of disorders in the circulatory system in the course of portal hypertension. It is characterized by impaired left ventricular systolic and diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. However, signs and symptoms reported by patients are non-specific and include reduced exercise tolerance, fatigue, peripheral oedema, and ascites. The disease usually remains asymptomatic with almost normal heart function, unless patients are exposed to stress or exertion. Unfortunately, due to the subclinical course, CCM is rarely recognized. Orthotopic liver transplantation (OLTx) seems to improve circulatory function although there is no consensus about its positive effect, with reported cases of heart failure onset after transplantation. Researchers indicate a careful pre-, peri-, and post-transplant cardiac assessment as a crucial point in detecting CCM and improving patients’ prognosis. There is also an urgent need to update the CCM definition and establish a diagnostic algorithm for early diagnosis of CCM as well as a specific treatment of this condition.
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Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis. Int J Hepatol 2021; 2021:5592376. [PMID: 34900353 PMCID: PMC8660240 DOI: 10.1155/2021/5592376] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 11/17/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcome of liver transplantation or TIPS insertion, a few Indian studies have addressed the role of LVDD on survival in decompensated cirrhosis. The objective of this study is to assess the effect of LVDD on the survival of decompensated cirrhotic patients. METHODS We prospectively evaluated 92 decompensated cirrhotic patients from April 2015 to March 2017 at IMS and SUM Hospital, Bhubaneswar, India. 2D echocardiography with tissue Doppler imaging was used to evaluate cardiac function, as per the American society of echocardiography guidelines. The primary endpoint was to evaluate the effect of LVDD on overall mortality. RESULTS Ninety-two decompensated cirrhotic patients were evaluated in this prospective cohort study. Twenty-eight out of 92 patients (30%) died due to liver-related complications after a follow-up of 24 months. The decompensated cirrhotic patients with MELD score ≥ 15 had a significantly higher E/e' ratio (11.94 ± 4.24 vs. 8.74 ± 3.32, p < 0.001) suggesting severe LV dysfunction in advanced cirrhosis. Patients with E/e' ratio > 10 had significantly higher MELD score and Child-Pugh score (19.88 ± 7.72 vs. 14.31 ± 5.83; 10.25 ± 1.74 vs. 9.02 ± 1.74, p < 0.01, respectively) as compared to theE/e' ratio < 10 group. In Cox proportional hazard multivariate analysis, E/e' ≥ 10 (HR 2.72, 95% CI 1.07-6.9, p = 0.03) and serum albumin (HR 0.32, 95% CI 0.14-0.7, p < 0.01) were found to be independent predictors of mortality in decompensated cirrhotic patients. CONCLUSION : The presence of LVDD and low serum albumin were independent predictors of mortality in decompensated cirrhotic patients. Hence, LVDD is an indicator of advanced cirrhosis and mortality.
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Guglin M, Nazif K. New onset nonischemic cardiomyopathy post liver transplantation. Heart Fail Rev 2021; 27:1829-1836. [PMID: 34799813 DOI: 10.1007/s10741-021-10196-5] [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] [Accepted: 11/11/2021] [Indexed: 11/25/2022]
Abstract
A new onset acute heart failure (HF) with a sudden drop in the left ventricular ejection fraction (LVEF) post orthotopic liver transplant (LT) is a rare but a potentially fatal complication. Because in most of the cases there is no evidence of coronary thrombosis, it can be classified as nonischemic cardiomyopathy. More specifically, clinical presentation of this syndrome shares many features with stress-induced or takotsubo cardiomyopathy. The known factors that predispose these patients to acute HF during or shortly after LT include cirrhotic cardiomyopathy, rapid hemodynamic changes during LT surgery, and the large concentrations of catecholamines, either administered or released endogenously during surgery. The hemodynamic changes during surgery, such as the drop in preload during the anhepatic phase (occasionally requiring massive transfusions and vasopressors) and subsequent increase in preload with acidic and hyperkalemic plasma in the reperfusion phase, lead to rapid electrolyte and hemodynamic shifts. In several cases, intraoperative onset of HF, with or without ventricular arrythmia, could be timed to the reperfusion phase (and occasionally in the anhepatic and pre-anhepatic phases). In other cases, the HF syndrome started hours to days post-surgery. Recovery of cardiac function occurred in the majority of patients during the same admission; however, these patients generally need significantly longer hospitalizations and aggressive supportive care (occasionally requiring mechanical ionotropic and ventilatory support). If recover, the patients have a similar 1-year mortality as those LT patients that did not have this complication. Because no reliable risk stratification currently exists, intraoperative transesophageal echocardiography might be the most dependable way of detecting and addressing this syndrome promptly. Given the mechanism of takotsubo cardiomyopathy, beta-blockade and a preferential use of non-catecholaminergic vasopressors may be a reasonable way to manage this syndrome.
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Affiliation(s)
- Maya Guglin
- Krannert Institute of Cardiology, Indiana University School of Medicine, 1801 Senate Blvd Suite 2000, Indianapolis, IN, 46202, USA
| | - Kutaiba Nazif
- Krannert Institute of Cardiology, Indiana University School of Medicine, 1801 Senate Blvd Suite 2000, Indianapolis, IN, 46202, USA
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Ciccarelli M, Dawson D, Falcao-Pires I, Giacca M, Hamdani N, Heymans S, Hooghiemstra A, Leeuwis A, Hermkens D, Tocchetti CG, van der Velden J, Zacchigna S, Thum T. Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function. Cardiovasc Res 2021; 117:2416-2433. [PMID: 33483724 PMCID: PMC8562335 DOI: 10.1093/cvr/cvab009] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/20/2021] [Accepted: 01/08/2021] [Indexed: 12/13/2022] Open
Abstract
Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.
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Affiliation(s)
- Michele Ciccarelli
- University of Salerno, Department of Medicine, Surgery and Dentistry, Via S. Allende 1, 84081, Baronissi(Salerno), Italy
| | - Dana Dawson
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2DZ, UK
| | - Inês Falcao-Pires
- Department of Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
| | - Mauro Giacca
- King’s College London, Molecular Medicine Laboratory, 125 Caldharbour Lane, London WC2R2LS, United Kingdom
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Strada di Fiume, 447, 34129 Trieste, Italy
| | - Nazha Hamdani
- Department of Clinical Pharmacology and Molecular Cardiology, Institute of Physiology, Ruhr University Bochum, Universitätsstraße 150, D-44801 Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, Ruhr University Bochum, Universitätsstraße 150, D-44801 Bochum, Germany
| | - Stéphane Heymans
- Centre for Molecular and Vascular Biology, KU Leuven, Herestraat 49, Bus 911, 3000 Leuven, Belgium
- Department of Cardiology, Maastricht University, CARIM School for Cardiovascular Diseases, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands
- ICIN-Netherlands Heart Institute, Holland Heart House, Moreelsepark 1, 3511 EP Utrecht, the Netherlands
| | - Astrid Hooghiemstra
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1118, 1081HZ, Amsterdam, The Netherlands
- Department of Medical Humanities, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, De Boelelaan 1089a, 1081HV, Amsterdam, The Netherlands
| | - Annebet Leeuwis
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1118, 1081HZ, Amsterdam, The Netherlands
| | - Dorien Hermkens
- Department of Pathology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, the Netherlands
| | - Carlo Gabriele Tocchetti
- Department of Translational Medical Sciences and Interdepartmental Center of Clinical and Translational Research (CIRCET), Federico II University, Naples, Italy
| | - Jolanda van der Velden
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Physiology, Amsterdam Cardiovascular Sciences, De Boelelaan 1118, 1081HZ Amsterdam, the Netherlands
| | - Serena Zacchigna
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Strada di Fiume, 447, 34129 Trieste, Italy
- Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
- REBIRTH Center for Translational Regenerative Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
- Fraunhofer Institute of Toxicology and Experimental Medicine, Nicolai-Fuchs-Str. 1, D-30625 Hannover, Germany
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45
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Tannuri ACA, Chavez LS, Guimarães JX, Gonçalves JDO, Serafini S, Souza GCD, Malheiros DMAC, Paes VR, Tannuri U. Cardiac and renal effects of liver cirrhosis in a growing animal model. Acta Cir Bras 2021; 36:e360806. [PMID: 34644774 PMCID: PMC8516424 DOI: 10.1590/acb360806] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 07/02/2021] [Indexed: 11/22/2022] Open
Abstract
PURPOSE To assess the biochemical, histological, histomorphometric and molecular effects of biliary duct ligation (BDL) induced liver cirrhosis in the heart and kidneys. METHODS Thirty-two weaning rats (21 days old, 50-70 g) underwent BDL and were divided in four groups (euthanasia after two, four, six, and eight weeks, respectively) and compared to control groups. RESULTS The animals' hearts of group 3 were bigger than those of the control group (p=0.042), including thinner right ventricle wall, decreased internal diameter of ventricles, and increased perivascular collagen deposition in left ventricle, as well as increased interstitial collagen in right ventricle after six weeks. In the kidneys of groups 3 and 4, bilirubin impregnation in the tubules, hydropic degeneration, loss of nuclei and lack of plasmatic membrane limits were noted. Nitric oxide synthase (NOS) gene expressions were higher in group 1 (p=0.008), and endothelial nitric oxide synthase (eNOS) gene expressions were elevated in all experimental groups (p=0.008, p=0.001, p=0.022, and p=0.013, respectively). In the heart, a decreased expression of eNOS in group 1 (p=0.04) was observed. CONCLUSIONS Liver cirrhosis leads to histological and histomorphometric alterations in the heart and kidneys, with changes in the NOS and eNOS gene expressions, that may suggest a role in the associated myocardial and renal manifestations.
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46
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Chouhan MD, Fitzke HE, Bainbridge A, Atkinson D, Halligan S, Davies N, Lythgoe MF, Mookerjee RP, Menys A, Taylor SA. Cardiac-induced liver deformation as a measure of liver stiffness using dynamic imaging without magnetization tagging-preclinical proof-of-concept, clinical translation, reproducibility and feasibility in patients with cirrhosis. Abdom Radiol (NY) 2021; 46:4660-4670. [PMID: 34148103 DOI: 10.1007/s00261-021-03168-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 06/03/2021] [Accepted: 06/05/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE MR elastography and magnetization-tagging use liver stiffness (LS) measurements to diagnose fibrosis but require physical drivers, specialist sequences and post-processing. Here we evaluate non-rigid registration of dynamic two-dimensional cine MRI images to measure cardiac-induced liver deformation (LD) as a measure of LS by (i) assessing preclinical proof-of-concept, (ii) clinical reproducibility and inter-reader variability, (iii) the effects of hepatic hemodynamic changes and (iv) feasibility in patients with cirrhosis. METHODS Sprague-Dawley rats (n = 21 bile duct ligated (BDL), n = 17 sham-operated controls) and fasted patients with liver cirrhosis (n = 11) and healthy volunteers (HVs, n = 10) underwent spoiled gradient-echo short-axis cardiac cine MRI studies at 9.4 T (rodents) and 3.0 T (humans). LD measurements were obtained from intrahepatic sub-cardiac regions-of-interest close to the diaphragmatic margin. One-week reproducibility and prandial stress induced hemodynamic changes were assessed in healthy volunteers. RESULTS Normalized LD was higher in BDL (1.304 ± 0.062) compared with sham-operated rats (1.058 ± 0.045, P = 0.0031). HV seven-day reproducibility Bland-Altman (BA) limits-of-agreement (LoAs) were ± 0.028 a.u. and inter-reader variability BA LoAs were ± 0.030 a.u. Post-prandial LD increases were non-significant (+ 0.0083 ± 0.0076 a.u., P = 0.3028) and uncorrelated with PV flow changes (r = 0.42, p = 0.2219). LD measurements successfully obtained from all patients were not significantly higher in cirrhotics (0.102 ± 0.0099 a.u.) compared with HVs (0.080 ± 0.0063 a.u., P = 0.0847). CONCLUSION Cardiac-induced LD is a conceptually reasonable approach from preclinical studies, measurements demonstrate good reproducibility and inter-reader variability, are less likely to be affected by hepatic hemodynamic changes and are feasible in patients with cirrhosis.
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Affiliation(s)
- Manil D Chouhan
- Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK.
| | - Heather E Fitzke
- Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK
- Wingate Institute of Neurogastroenterology, Neuroscience and Trauma, Queen Mary University of London (QMUL), London, UK
| | - Alan Bainbridge
- Department of Medical Physics, University College London Hospitals NHS Trust, London, UK
| | - David Atkinson
- Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK
| | - Steve Halligan
- Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK
| | - Nathan Davies
- Division of Medicine, Institute for Liver and Digestive Health, University College London (UCL), London, UK
| | - Mark F Lythgoe
- Division of Medicine, Centre for Advanced Biomedical Imaging, University College London (UCL), London, UK
| | - Rajeshwar P Mookerjee
- Division of Medicine, Institute for Liver and Digestive Health, University College London (UCL), London, UK
| | - Alex Menys
- Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK
- Motilent, London, UK
| | - Stuart A Taylor
- Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK
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47
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Kasper P, Steffen HM, Michels G. [Cirrhotic cardiomyopathy]. Dtsch Med Wochenschr 2021; 146:1070-1076. [PMID: 34416775 DOI: 10.1055/a-1321-9523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
A cirrhotic cardiomyopathy (CCM) can be observed in patients with end-stage liver disease and is characterized by a systolic and/or diastolic dysfunction in the absence of pre-existing heart diseases. While the cardiac dysfunction is often masked at rest, it typically manifests itself during cardiovascular challenges such as hypovolemia, physical stress, or sepsis. The diagnosis of CCM is challenging and predominantly based on echocardiographic measurements to identify subclinical cardiac dysfunction. Additional diagnostic criteria include electrophysiological abnormalities such as QT-interval prolongation, an abnormal chronotropic or inotropic response to stress, elevated cardiac biomarkers such as natriuretic peptides, and structural cardiac abnormalities like left atrium enlargement. There is no specific therapy for CCM. Supportive measures and regular cardiac evaluation of high-risk patients and transplant candidates are important to reduce the risks associated with invasive procedures and treatments.
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48
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Not for the Faint of Heart. Ann Am Thorac Soc 2021; 18:519-523. [PMID: 33646074 DOI: 10.1513/annalsats.202007-817cc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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49
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de Souza SLB, Mota GAF, Gregolin CS, do Nascimento M, Luvizotto RAM, Bazan SGZ, Sugizaki MM, Barbisan LF, Cicogna AC, do Nascimento AF. Exercise Training Attenuates Cirrhotic Cardiomyopathy. J Cardiovasc Transl Res 2021; 14:674-684. [PMID: 32246321 DOI: 10.1007/s12265-020-09997-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 03/25/2020] [Indexed: 12/22/2022]
Abstract
Cirrhotic cardiomyopathy is a condition where liver cirrhosis is associated with cardiac dysfunction. Triggers and blockers of cirrhotic cardiomyopathy are poorly understood, which might compromise the prognosis of chronic liver disease patients. We tested whether exercise training would reduce liver damage induced by thioacetamide and prevent liver cirrhosis-associated cardiomyopathy. Wistar rats were divided into three groups: control, thioacetamide (TAA), or TAA plus exercise. Thioacetamide increased liver weight and serum alanine aminotransferase and aspartate aminotransferase levels. Also, TAA treatment was involved with hepatic nodule formation, fibrotic septa, inflammatory infiltration, and hepatocyte necrosis. The exercise group presented with a reduction in liver injury status. We found that liver injury was associated with disordered cardiac hypertrophy as well as diastolic and systolic dysfunction. Exercise training attenuated cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment. These results provided insights that exercise training can mitigate cirrhotic cardiomyopathy phenotype. Graphical Abstract Exercise training attenuated liver injury as well as cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment.
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Affiliation(s)
- Sérgio Luiz Borges de Souza
- Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Gustavo Augusto Ferreira Mota
- Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Cristina Schmitt Gregolin
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial, Sinop, Mato Grosso, 78.556-267, Brazil
| | - Milena do Nascimento
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial, Sinop, Mato Grosso, 78.556-267, Brazil
| | - Renata Azevedo Melo Luvizotto
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial, Sinop, Mato Grosso, 78.556-267, Brazil
| | - Silmeia Garcia Zanati Bazan
- Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Mário Mateus Sugizaki
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial, Sinop, Mato Grosso, 78.556-267, Brazil
| | - Luis Fernando Barbisan
- Department of Morphology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Antonio Carlos Cicogna
- Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - André Ferreira do Nascimento
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial, Sinop, Mato Grosso, 78.556-267, Brazil.
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50
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Koshy AN, Gow PJ, Han HC, Teh AW, Jones R, Testro A, Lim HS, McCaughan G, Jeffrey GP, Crawford M, Macdonald G, Fawcett J, Wigg A, Chen JWC, Gane EJ, Munn SR, Clark DJ, Yudi MB, Farouque O. Cardiovascular mortality following liver transplantation: predictors and temporal trends over 30 years. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2021; 6:243-253. [PMID: 32011663 DOI: 10.1093/ehjqcco/qcaa009] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 01/21/2020] [Accepted: 01/24/2020] [Indexed: 12/13/2022]
Abstract
AIMS There has been significant evolution in operative and post-transplant therapies following liver transplantation (LT). We sought to study their impact on cardiovascular (CV) mortality, particularly in the longer term. METHODS AND RESULTS A retrospective cohort study was conducted of all adult LTs in Australia and New Zealand across three 11-year eras from 1985 to assess prevalence, modes, and predictors of early (≤30 days) and late (>30 days) CV mortality. A total of 4265 patients were followed-up for 37 409 person-years. Overall, 1328 patients died, and CV mortality accounted for 228 (17.2%) deaths. Both early and late CV mortality fell significantly across the eras (P < 0.001). However, CV aetiologies were consistently the leading cause of early mortality and accounted for ∼40% of early deaths in the contemporary era. Cardiovascular deaths occurred significantly later than non-cardiac aetiologies (8.8 vs. 5.2 years, P < 0.001). On multivariable Cox regression, coronary artery disease [hazard ratio (HR) 4.6, 95% confidence interval (CI) 1.2-21.6; P = 0.04] and era of transplantation (HR 0.44; 95% CI 0.28-0.70; P = 0.01) were predictors of early CV mortality, while advancing age (HR 1.05, 95% CI 1.02-1.10; P = 0.005) was an independent predictors of late CV mortality. Most common modes of CV death were cardiac arrest, cerebrovascular events, and myocardial infarction. CONCLUSION Despite reductions in CV mortality post-LT over 30 years, they still account for a substantial proportion of early and late deaths. The late occurrence of CV deaths highlights the importance of longitudinal follow-up to study the efficacy of targeted risk-reduction strategies in this unique patient population.
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Affiliation(s)
- Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Hui-Chen Han
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Andrew W Teh
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Robert Jones
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Adam Testro
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Han S Lim
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Geoffrey McCaughan
- Department of Liver Transplantation, Royal Prince Alfred Hospital, Sydney, Australia.,University of Sydney, Sydney, Australia
| | - Gary P Jeffrey
- Department of Liver Transplantation, Sir Charles Gardiner Hospital, Perth, Australia.,School of Medicine, University of Western Australia, Nedlands, Australia
| | - Michael Crawford
- Department of Liver Transplantation, Royal Prince Alfred Hospital, Sydney, Australia.,University of Sydney, Sydney, Australia
| | - Graeme Macdonald
- Department of Liver Transplantation, Princess Alexandra Hospital, Brisbane, Australia.,School of Medicine, The University of Queensland, Brisbane, Australia
| | - Jonathan Fawcett
- Department of Liver Transplantation, Princess Alexandra Hospital, Brisbane, Australia.,School of Medicine, The University of Queensland, Brisbane, Australia
| | - Alan Wigg
- Department of Liver Transplantation, Flinders Medical Centre, Adelaide, Australia
| | - John W C Chen
- Department of Liver Transplantation, Flinders Medical Centre, Adelaide, Australia
| | | | | | - David J Clark
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Matias B Yudi
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
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