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Gupta T, Saini A, Gaur V, Goel A. Comparative Study of Terlipressin and Noradrenaline as Vasopressors in Patients With Acute-on-chronic Liver Failure and Septic Shock: A Randomized Controlled Trial. J Clin Exp Hepatol 2025; 15:102494. [PMID: 39980577 PMCID: PMC11836504 DOI: 10.1016/j.jceh.2024.102494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 12/15/2024] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Sepsis is the most common acute insult in patients with acute-on-chronic liver failure (ACLF), and circulatory failure portends a poor prognosis in them. AIM This study aimed to compare terlipressin and noradrenaline as first-line vasopressors in patients with ACLF and septic shock. METHODS This prospective, open-label, randomized controlled study was conducted from January 2021 to June 2022 at a tertiary care center. All patients presenting with ACLF as per the chronic liver failure consortium acute on chronic liver failure in cirrhosis study and septic shock were screened. Shock was defined as a mean arterial pressure (MAP) <65 mmHg/systolic blood pressure <90 mmHg. Patients with septic shock nonresponsive to crystalloids/colloids were randomized to receive terlipressin (group I) at 2.6 μg/kg/min and noradrenaline (group II) at 0.1 μg/kg/min. The primary outcome was an MAP >65 mmHg at 6 h. The secondary outcomes were 3-, 7-, 14-, and 28-day mortality, duration of hospital stay, cumulative dose of drug, and new events such as upper gastrointestinal bleed, acute kidney injury, jaundice, and hepatic encephalopathy within 28 days. RESULTS A total of 70 patients were randomized to group I (n = 35) and group II (n = 35). According to per-protocol analysis, a higher number of patients achieved an MAP > 65 mmHg at 6 h in group II (n = 23/31, 74%) than in group I (5/34, 14%) (P < 0.001). The 3-and 7-day mortality was significantly higher in group I than in group II, with no difference at 14 and 28 days. The 28-day mortality was highest in ACLF grade-3 in both group II (22/25, 88%) and group I (15/20, 75%). CONCLUSION Terlipressin did not prove to be noninferior to norepinephrine, and therefore, norepinephrine should be the first-line vasopressor in ACLF patients with septic shock. The mortality rate was highest in ACLF grade-3 patients in both the groups, irrespective of the initial response to vasopressors. This indicates that holistic management of these patients is most important.
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Affiliation(s)
- Tarana Gupta
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Anjali Saini
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Vaibhav Gaur
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Ashank Goel
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
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Myers S, Gupta DK, Izzy M. The clinical relevance of the new criteria for cirrhotic cardiomyopathy and future directions. Liver Transpl 2025; 31:521-530. [PMID: 39185907 DOI: 10.1097/lvt.0000000000000458] [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] [Received: 04/23/2024] [Accepted: 08/05/2024] [Indexed: 08/27/2024]
Abstract
Cardiac dysfunction in patients with liver disease has been recognized since the 1950s. Initially attributed to shared risk factors, it is now evident that cardiac dysfunction in patients with cirrhosis can occur in the absence of known cardiac, that is, coronary artery and valvular heart disease, and across all etiologies for cirrhosis. In 1996, this myocardial dysfunction was termed cirrhotic cardiomyopathy (CCM). The pathophysiologic mechanisms underlying CCM include impaired beta-adrenergic membrane function and circulating proinflammatory and cardiotoxic substances. In 2005, the first diagnostic criteria for CCM were introduced enabling greater sensitivity and accuracy of diagnosis. Since 2005, advancements in echocardiographic methods and a better understanding of the pathophysiology of cardiac dysfunction in patients with cirrhosis necessitated a revision of CCM criteria. Changes in CCM criteria included the removal of blunted contractile or heart rate response on stress testing and the addition of global longitudinal systolic strain. The refinement of criteria for diastolic dysfunction was also incorporated into the new diagnostic approach. Since 2020, the prevalence of the disorder and clinical considerations for pretransplant, peritransplant, and posttransplant patients with cirrhosis have been further evaluated, and CCM was found to adversely impact clinical outcomes during all 3 phases of care. Future research considerations should address the timing of universal echocardiographic screening for patients with cirrhosis, the utility of biomarkers in aiding CCM diagnosis, the impact of CCM on right heart function, and the role of anti-remodeling agents after liver transplant.
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Affiliation(s)
- Sarah Myers
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Deepak K Gupta
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Manhal Izzy
- Division of Gastroenterology, Department of Medicine, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Ryu DG, Yu F, Yoon KT, Liu H, Lee SS. The Cardiomyocyte in Cirrhosis: Pathogenic Mechanisms Underlying Cirrhotic Cardiomyopathy. Rev Cardiovasc Med 2024; 25:457. [PMID: 39742234 PMCID: PMC11683693 DOI: 10.31083/j.rcm2512457] [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: 07/11/2024] [Revised: 08/28/2024] [Accepted: 09/10/2024] [Indexed: 01/03/2025] Open
Abstract
Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunction in patients with cirrhosis, in the absence of any primary heart disease. These changes are mainly due to the malfunction or abnormalities of cardiomyocytes. Similar to non-cirrhotic heart failure, cardiomyocytes in cirrhotic cardiomyopathy demonstrate a variety of abnormalities: from the cell membrane to the cytosol and nucleus. At the cell membrane level, biophysical plasma membrane fluidity, and membrane-bound receptors such as the beta-adrenergic, muscarinic and cannabinoid receptors are abnormal either functionally or structurally. Other changes include ion channels such as L-type calcium channels, potassium channels, and sodium transporters. In the cytosol, calcium release and uptake processes are dysfunctional and the myofilaments such as myosin heavy chain and titin, are either functionally abnormal or have structural alterations. Like the fibrotic liver, the heart in cirrhosis also shows fibrotic changes such as a collagen isoform switch from more compliant collagen III to stiffer collagen I which also impacts diastolic function. Other abnormalities include the secondary messenger cyclic adenosine monophosphate, cyclic guanosine monophosphate, and their downstream effectors such as protein kinase A and G-proteins. Finally, other changes such as excessive apoptosis of cardiomyocytes also play a critical role in the pathogenesis of cirrhotic cardiomyopathy. The present review aims to summarize these changes and review their critical role in the pathogenesis of cirrhotic cardiomyopathy.
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Affiliation(s)
- Dae Gon Ryu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
- Division of Gastroenterology, Yangsan Hospital, Pusan National University Faculty of Medicine, 50612 Pusan, Republic of Korea
| | - Fengxue Yu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
- Telemedicine Center, Second Hospital of Hebei Medical University, 050004 Shijiazhuang, Hebei, China
| | - Ki Tae Yoon
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
- Division of Gastroenterology, Yangsan Hospital, Pusan National University Faculty of Medicine, 50612 Pusan, Republic of Korea
| | - Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
| | - Samuel S. Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
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4
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Liu H, Ryu D, Hwang S, Lee SS. Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities. Int J Mol Sci 2024; 25:5849. [PMID: 38892040 PMCID: PMC11173074 DOI: 10.3390/ijms25115849] [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: 05/03/2024] [Revised: 05/23/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.
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Affiliation(s)
- Hongqun Liu
- Liver Unit, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; (H.L.); (D.R.); (S.H.)
| | - Daegon Ryu
- Liver Unit, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; (H.L.); (D.R.); (S.H.)
- Division of Gastroenterology, Yangsan Hospital, Pusan National University School of Medicine, Pusan 46033, Republic of Korea
| | - Sangyoun Hwang
- Liver Unit, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; (H.L.); (D.R.); (S.H.)
- Department of Internal Medicine, Dongnam Institute of Radiological and Medical Sciences, Pusan 46033, Republic of Korea
| | - Samuel S. Lee
- Liver Unit, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; (H.L.); (D.R.); (S.H.)
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Billig S, Hein M, Kirchner C, Schumacher D, Habigt MA, Mechelinck M, Fuchs D, Klinge U, Theißen A, Beckers C, Bleilevens C, Kramann R, Uhlig M. Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury. Biomedicines 2024; 12:876. [PMID: 38672230 PMCID: PMC11048529 DOI: 10.3390/biomedicines12040876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 04/08/2024] [Accepted: 04/14/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality. METHODS We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male Sprague-Dawley rats were subjected to BDL surgery (n = 28) or served as sham-operated (n = 9) controls. Transthoracic echocardiography, Doppler evaluation of the left anterior descending coronary artery, and myocardial contrast echocardiography were performed at rest and during adenosine and dobutamine stress 5 days after BDL. Immunohistochemical staining of myocardial tissue samples for hypoxia and inflammation as well as serum analysis were performed. RESULTS BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; p < 0.001). Concurrently, cardiac function was significantly impaired, characterized by reduced cardiac output (CO) and global longitudinal strain (GLS) in the echocardiography at rest and under pharmacological stress (CO rest control: 120.6 ± 24.3 mL/min vs. BDL 102.5 ± 16.6 mL/min, p = 0.041; GLS rest control: -24.05 ± 3.8% vs. BDL: -18.5 ± 5.1%, p = 0.01). Myocardial perfusion analysis revealed a reduced myocardial blood flow at rest and a decreased coronary flow velocity reserve (CFVR) under dobutamine stress in the BDL animals (CFVR control: 2.1 ± 0.6 vs. BDL: 1.7 ± 0.5 p = 0.047). Immunofluorescence staining indicated myocardial hypoxia and increased neutrophil infiltration. CONCLUSIONS In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.
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Affiliation(s)
- Sebastian Billig
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Marc Hein
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Celine Kirchner
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - David Schumacher
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
- Department of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany
| | - Moriz Aljoscha Habigt
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Mare Mechelinck
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Dieter Fuchs
- FUJIFILM VisualSonics, Inc., Joop Geesinkweg 140, 1114 AB Amsterdam, The Netherlands
| | - Uwe Klinge
- Department of General, Visceral and Transplantation Surgery, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany
| | - Alexander Theißen
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Christian Beckers
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Christian Bleilevens
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
| | - Rafael Kramann
- Department of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany
| | - Moritz Uhlig
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany (C.B.)
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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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7
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Ketabchi F, Khoram M, Dehghanian A. Evaluation of Electrocardiogram Parameters and Heart Rate Variability During Blood Pressure Elevation by Phenylephrine in Cirrhotic Rats. Cardiovasc Toxicol 2024; 24:321-334. [PMID: 38409566 DOI: 10.1007/s12012-024-09839-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 02/07/2024] [Indexed: 02/28/2024]
Abstract
Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44 days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10 μg/μl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100 μg/ml/5 min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group.ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis.
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Affiliation(s)
- Farzaneh Ketabchi
- Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mohammadreza Khoram
- Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirreza Dehghanian
- Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Liu H, Naser JA, Lin G, Lee SS. Cardiomyopathy in cirrhosis: From pathophysiology to clinical care. JHEP Rep 2024; 6:100911. [PMID: 38089549 PMCID: PMC10711481 DOI: 10.1016/j.jhepr.2023.100911] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 08/24/2023] [Accepted: 08/31/2023] [Indexed: 01/12/2024] Open
Abstract
Cirrhotic cardiomyopathy (CCM) is defined as systolic or diastolic dysfunction in the absence of prior heart disease or another identifiable cause in patients with cirrhosis, in whom it is an important determinant of outcome. Its underlying pathogenic/pathophysiological mechanisms are rooted in two distinct pathways: 1) factors associated with portal hypertension, hyperdynamic circulation, gut bacterial/endotoxin translocation and the resultant inflammatory phenotype; 2) hepatocellular insufficiency with altered synthesis or metabolism of substances such as proteins, lipids, carbohydrates, bile acids and hormones. Different criteria have been proposed to diagnose CCM; the first in 2005 by the World Congress of Gastroenterology, and more recently in 2019 by the Cirrhotic Cardiomyopathy Consortium. These criteria mainly utilised echocardiographic evaluation, with the latter refining the evaluation of diastolic function and integrating global longitudinal strain into the evaluation of systolic function, an important addition since the haemodynamic changes that occur in advanced cirrhosis may lead to overestimation of systolic function by left ventricular ejection fraction. Advances in cardiac imaging, such as cardiac magnetic resonance imaging and the incorporation of an exercise challenge, may help further refine the diagnosis of CCM. Over recent years, CCM has been shown to contribute to increased mortality and morbidity after major interventions, such as liver transplantation and transjugular intrahepatic portosystemic shunt insertion, and to play a pathophysiologic role in the genesis of hepatorenal syndrome. In this review, we discuss the pathogenesis/pathophysiology of CCM, its clinical implications, and the role of cardiac imaging modalities including MRI. We also compare diagnostic criteria and review the potential diagnostic role of electrocardiographic QT prolongation. At present, no definitive medical therapy exists, but some promising potential treatment strategies for CCM are reviewed.
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Affiliation(s)
- Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Jwan A. Naser
- Division of Cardiology, Mayo Clinic, Rochester, MN, USA
| | - Grace Lin
- Division of Cardiology, Mayo Clinic, Rochester, MN, USA
| | - Samuel S. Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
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Hwang SY, Liu H, Lee SS. Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy. Biomedicines 2023; 11:1895. [PMID: 37509534 PMCID: PMC10377313 DOI: 10.3390/biomedicines11071895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/30/2023] Open
Abstract
Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy.
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Affiliation(s)
- Sang Youn Hwang
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
- Department of Internal Medicine, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, Republic of Korea
| | - Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
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10
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Lee W, Vandenberk B, Raj SR, Lee SS. Prolonged QT Interval in Cirrhosis: Twisting Time? Gut Liver 2022; 16:849-860. [PMID: 35864808 PMCID: PMC9668500 DOI: 10.5009/gnl210537] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 12/07/2021] [Indexed: 11/04/2022] Open
Abstract
Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of ventricular arrhythmias, such as torsade de pointes (TdP). In cirrhotic patients, there is likely a significant association between the corrected QT (QTc) interval and the severity of liver disease, and possibly with increased mortality. We present a stepwise overview of the pathophysiology and management of acquired long QT syndrome in cirrhosis. The QT interval is mainly determined by ventricular repolarization. To compare the QT interval in time it should be corrected for heart rate (QTc), preferably by the Fridericia method. A QTc interval >450 ms in males and >470 ms in females is considered prolonged. The pathophysiological mechanism remains incompletely understood, but may include metabolic, autonomic or hormonal imbalances, cirrhotic heart failure and/or genetic predisposition. Additional external risk factors for QTc prolongation include medication (IKr blockade and altered cytochrome P450 activity), bradycardia, electrolyte abnormalities, underlying cardiomyopathy and acute illness. In patients with cirrhosis, multiple hits and cardiac-hepatic interactions are often required to sufficiently erode the repolarization reserve before long QT syndrome and TdP can occur. While some risk factors are unavoidable, overall risk can be mitigated by electrocardiogram monitoring and avoiding drug interactions and electrolyte and acidbase disturbances. In cirrhotic patients with prolonged QTc interval, a joint effort by cardiologists and hepatologists may be useful and significantly improve the clinical course and outcome.
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Affiliation(s)
- William Lee
- Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- St Vincent's Clinical School, University of New South Wales, Sydney, Australia
| | - Bert Vandenberk
- Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Satish R. Raj
- Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Samuel S. Lee
- Liver Unit, Snyder Institute for Chronic Disease, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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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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12
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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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Chen T, Huang Z, Chen W, Ding R, Li N, Cui H, Wu F, Liang C, Cong X. Potential cardioprotective influence of bupropion against CCl4-triggered cirrhotic cardiomyopathy. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2021.103599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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14
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Amanuel T, Zelalem B. QT Interval Prolongation Among Patients with Chronic Liver Disease Attending Jimma Medical Center Gastroenterology Clinic, Southwest Ethiopia. RESEARCH REPORTS IN CLINICAL CARDIOLOGY 2022. [DOI: 10.2147/rrcc.s345825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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15
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Desai MS. Mechanistic insights into the pathophysiology of cirrhotic cardiomyopathy. Anal Biochem 2021; 636:114388. [PMID: 34587512 DOI: 10.1016/j.ab.2021.114388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 08/22/2021] [Accepted: 09/15/2021] [Indexed: 02/08/2023]
Abstract
Myocardial dysfunction in end stage cirrhotic liver disease, termed cirrhotic cardiomyopathy, is a long known, but little understood comorbidity seen in ∼50% of adults and children who present for liver transplantation. Structural, functional, hemodynamic and electrocardiographic aberrations that occur in the heart as a direct consequence of a damaged liver, is associated with multi-organ failure and increased mortality and morbidity in patients undergoing surgical procedures such as porto-systemic shunt placement and liver transplantation. Despite its clinical significance and rapid advances in science and pharmacotherapy, there is yet no specific treatment for this disease. This may be due to a lack of understanding of the pathogenesis and mechanisms behind how a cirrhotic liver causes cardiac pathology. This review will focus specifically on insights into the molecular mechanisms that drive this liver-heart interaction. Deeper understanding of the etio-pathogenesis of cirrhotic cardiomyopathy will allow us to design and test treatments that can be targeted to prevent and/or reverse this co-morbid consequence of liver failure and improve health care delivery and outcomes in patients with cirrhosis.
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Affiliation(s)
- Moreshwar S Desai
- Department of Pediatrics, Section of Pediatric Critical Care Medicine and Liver ICU. Baylor College of Medicine, Houston, TX, 77030, USA.
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16
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Lee DU, Fan GH, Hastie DJ, Addonizio EA, Karagozian R. The clinical impact of paroxysmal arrhythmias on the hospital outcomes of patients admitted with cirrhosis: propensity score matched analysis of 2011-2017 US hospitals. Expert Rev Cardiovasc Ther 2021; 19:947-956. [PMID: 34493127 DOI: 10.1080/14779072.2021.1978841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND We evaluate the effects of paroxysmal arrhythmia on the hospital outcomes of patients admitted with cirrhosis. RESEARCH DESIGN AND METHODS 2011-2017 National Inpatient Sample was used to isolate patients with decompensated/compensated cirrhosis, stratified by paroxysmal arrhythmia (supraventricular: PSVT and ventricular: PVT). The cohorts were matched using propensity-score matching and compared to mortality, length of stay, cost, and cardiac complications (cardioversion, cardiogenic shock, cardiac arrest, and ventricular fibrillation). RESULTS In compensated cirrhosis, 2,453 had PSVT with matched controls; 5,274 had PVT with matched controls. Those with PSVT had higher mortality (aOR 1.55 95%CI 1.23-1.95) and higher rates of cardioversion and cardiogenic shock; likewise, those with PVT had higher mortality (aOR 2.41 95%CI 2.09-2.78) and higher rates of all complications. In decompensated cirrhosis, 1,598 had PSVT with matched controls; 4,178 had PVT with matched controls. Those with PSVT had higher mortality (aOR 1.57 95%CI 1.28-1.93) and higher rates of cardioversion, cardiogenic shock, cardiac arrest; those with PVT had higher mortality (aOR 2.25 95%CI 1.98-2.56) and higher rates of all complications. CONCLUSION The findings from this study show that in either decompensated or compensated cohort, those with paroxysmal arrhythmias are at a higher risk of in-hospital mortality and adverse cardiac outcomes.
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Affiliation(s)
- David Uihwan Lee
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Gregory Hongyuan Fan
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - David Jeffrey Hastie
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Elyse Ann Addonizio
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
| | - Raffi Karagozian
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
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Role of Anti-Beta-1-Adrenergic Receptor Antibodies in Cardiac Dysfunction in Patients with Cirrhotic Cardiomyopathy. J Cardiovasc Transl Res 2021; 15:381-390. [PMID: 34417673 DOI: 10.1007/s12265-021-10161-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 07/26/2021] [Indexed: 01/18/2023]
Abstract
Cirrhotic cardiomyopathy (CCM) is a recognized complication of cirrhosis and is associated with poor outcomes, especially under challenges such as surgery/liver transplantation. However, the mechanism is not clear, and the treatment is not specific. The present study aimed to evaluate the role of anti-β1-adrenergic receptor antibodies (anti-β1-AR) in CCM. We enrolled 3 groups: healthy controls, cirrhotic patients without CCM, and patients with CCM. We found that the anti-β1-AR levels in the CCM group were significantly higher than that in the non-CCM group; anti-β1-AR was positively correlated to NT-proBNP, negatively correlated to left ventricular ejection fraction, fractional shortening ((r = - 0.466, P < 0.05), and the ratio of peak early (E wave) and atrial (A wave) flow velocities (E/A (r = - 0.475, P < 0.05) in CCM patients. Anti-β1-AR is a useful predictive biomarker for the presence of CCM and eventually may also have therapeutic implications. Clinical Trials Registration: Chinese Clinical Trials No. ChiCTR 2,000,037,730.
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18
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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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Abstract
Cirrhotic cardiomyopathy (CCM), cardiac dysfunction in end-stage liver disease in the absence of prior heart disease, is an important clinical entity that contributes significantly to morbidity and mortality. The original definition for CCM, established in 2005 at the World Congress of Gastroenterology (WCG), was based upon known echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Subsequent advances in cardiovascular imaging and in particular myocardial deformation imaging have rendered the WCG criteria outdated. A number of investigations have explored other factors relevant to CCM, including serum markers, electrocardiography, and magnetic resonance imaging. CCM characteristics include a hyperdynamic circulatory state, impaired contractility, altered diastolic relaxation, and electrophysiological abnormalities, particularly QT interval prolongation. It is now known that cardiac dysfunction worsens with the progression of cirrhosis. Treatment for CCM has traditionally been limited to supportive efforts, but new pharmacological studies appear promising. Left ventricular diastolic dysfunction in CCM can be improved by targeted heart rate reduction. Ivabradine combined with carvedilol improves left ventricular diastolic dysfunction through targeted heart rate reduction, and this regimen can improve survival in patients with cirrhosis. Orthotopic liver transplantation also appears to improve CCM. Here, we canvass diagnostic challenges associated with CCM, introduce cardiac physiology principles and the application of echocardiographic techniques, and discuss the evidence behind therapeutic interventions in CCM.
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20
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Matyas C, Haskó G, Liaudet L, Trojnar E, Pacher P. Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications. Nat Rev Cardiol 2021; 18:117-135. [PMID: 32999450 DOI: 10.1038/s41569-020-0433-5] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/11/2020] [Indexed: 12/11/2022]
Abstract
The liver is a crucial metabolic organ that has a key role in maintaining immune and endocrine homeostasis. Accumulating evidence suggests that chronic liver disease might promote the development of various cardiac disorders (such as arrhythmias and cardiomyopathy) and circulatory complications (including systemic, splanchnic and pulmonary complications), which can eventually culminate in clinical conditions ranging from portal and pulmonary hypertension to pulmonary, cardiac and renal failure, ascites and encephalopathy. Liver diseases can affect cardiovascular function during the early stages of disease progression. The development of cardiovascular diseases in patients with chronic liver failure is associated with increased morbidity and mortality, and cardiovascular complications can in turn affect liver function and liver disease progression. Furthermore, numerous infectious, inflammatory, metabolic and genetic diseases, as well as alcohol abuse can also influence both hepatic and cardiovascular outcomes. In this Review, we highlight how chronic liver diseases and associated cardiovascular effects can influence different organ pathologies. Furthermore, we explore the potential roles of inflammation, oxidative stress, vasoactive mediator imbalance, dysregulated endocannabinoid and autonomic nervous systems and endothelial dysfunction in mediating the complex interplay between the liver and the systemic vasculature that results in the development of the extrahepatic complications of chronic liver disease. The roles of ageing, sex, the gut microbiome and organ transplantation in this complex interplay are also discussed.
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Affiliation(s)
- Csaba Matyas
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA
| | - György Haskó
- Department of Anesthesiology, Columbia University, New York, NY, USA
| | - Lucas Liaudet
- Department of Intensive Care Medicine and Burn Center, University Hospital Medical Center, Faculty of Biology and Medicine, Lausanne, Switzerland
| | - Eszter Trojnar
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA
| | - Pal Pacher
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA.
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Chelakkat M, Jacob M, Sebastian S, Paul G, NM A, Joy B, Afsal M. Echocardiographic abnormalities in patients with chronic liver disease: Observations from Thrissur, Kerala, India. MGM JOURNAL OF MEDICAL SCIENCES 2021. [DOI: 10.4103/mgmj.mgmj_84_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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22
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Cirrhotic Cardiomyopathy - A Veiled Threat. Cardiol Rev 2020; 30:80-89. [PMID: 33229904 DOI: 10.1097/crd.0000000000000377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction in patients with liver cirrhosis without pre-existing cardiac disease. According to the definition established by the World Congress of Gasteroenterology in 2005, the diagnosis of CCM includes criteria reflecting systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances. Because of minimal or even absent clinical symptoms and/or echocardiographic signs at rest according to the 2005 criteria, CCM diagnosis is often missed or delayed in most clinically-stable cirrhotic patients. However, cardiac dysfunction progresses in time and contributes to the pathogenesis of hepatorenal syndrome and increased morbidity and mortality after liver transplantation, surgery or other invasive procedures in cirrhotic patients. Therefore, a comprehensive cardiovascular assessment using newer techniques for echocardiographic evaluation of systolic and diastolic function, allowing the diagnosis of CCM in the early stage of subclinical cardiovascular dysfunction, should be included in the screening process of liver transplant candidates and patients with cirrhosis in general. The present review aims to summarize the most important pathophysiological aspects of CCM, the usefulness of contemporary cardiovascular imaging techniques and parameters in the diagnosis of CCM, the current therapeutic options, and the importance of early diagnosis of cardiovascular impairment in cirrhotic patients.
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23
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Myocardial Dysfunction in Cirrhotic Cardiomyopathy is Associated with Alterations of Phospholamban Phosphorylation and IL-6 Levels. Arch Med Res 2020; 52:284-293. [PMID: 33220932 DOI: 10.1016/j.arcmed.2020.11.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 10/16/2020] [Accepted: 11/05/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. AIM OF THE STUDY We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. METHODS Cirrhosis was induced by thioacetamide (TAA, 100 mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-α and IL-6 levels were measured by ELISA. RESULTS Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by in vivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. In vitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. CONCLUSIONS Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function.
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Isaak A, Praktiknjo M, Jansen C, Faron A, Sprinkart AM, Pieper CC, Chang J, Fimmers R, Meyer C, Dabir D, Thomas D, Trebicka J, Attenberger U, Kuetting D, Luetkens JA. Myocardial Fibrosis and Inflammation in Liver Cirrhosis: MRI Study of the Liver-Heart Axis. Radiology 2020; 297:51-61. [PMID: 32808886 DOI: 10.1148/radiol.2020201057] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Cardiac involvement in liver cirrhosis in the absence of underlying cardiac disease is termed cirrhotic cardiomyopathy. The pathophysiology of this condition is still poorly understood. Purpose To investigate the extent of subclinical imaging changes in terms of fibrosis and inflammation and to explore the relationship between the severity of liver disease and the degree of myocardial involvement. Materials and Methods In this prospective study from November 2018 to December 2019, participants with liver cirrhosis and healthy control participants underwent hepatic and cardiac MRI. The multiparametric scan protocol assessed hepatic (T1 and T2 relaxation times, extracellular volume [ECV], and MR elastography-based liver stiffness) and cardiac (T1 and T2 relaxation times, ECV, myocardial edema, late gadolinium enhancement [LGE], and myocardial strain) parameters. Student t tests, one-way analysis of variance, Pearson correlation, and multivariable binary regression analysis were used for statistical analyses. Results A total of 42 participants with liver cirrhosis (mean age ± standard deviation, 57 years ± 11; 23 men) and 18 control participants (mean age, 54 years ± 19; 11 men) were evaluated. Compared with control participants, the participants with liver cirrhosis displayed reduced longitudinal strain and elevated markers of myocardial disease (T1 and T2 relaxation times, ECV, and qualitative and quantitative LGE). Myocardial T1 (978 msec ± 23 vs 1006 msec ± 29 vs 1044 msec ± 14; P < .001) and T2 relaxation times (56 msec ± 4 vs 59 msec ± 3 vs 62 msec ± 8; P = .04) and ECV (30% ± 5 vs 33% ± 5 vs 38% ± 7; P = .009) were higher depending on Child-Pugh class (A vs B vs C). Positive LGE lesions (three of 11 [27%] vs 10 of 19 [53%] vs nine of 11 [82%]; P = .04) were more prevalent in advanced Child-Pugh classes. MR elastography-based liver stiffness was an independent predictor for LGE (odds ratio, 1.6; 95% confidence interval: 1.2%, 2.1%; P = .004) and correlated with quantitative LGE (r = 0.67; P < .001), myocardial T1 relaxation times (r = 0.55; P < .001), and ECV (r = 0.39; P = .01). Conclusion In participants with liver cirrhosis, systolic dysfunction and elevated parameters of myocardial edema and fibrosis were observed at MRI, which were more abnormal with greater severity of liver disease. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by de Roos and Lamb in this issue.
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Affiliation(s)
- Alexander Isaak
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Michael Praktiknjo
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Christian Jansen
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Anton Faron
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Alois M Sprinkart
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Claus C Pieper
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Johannes Chang
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Rolf Fimmers
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Carsten Meyer
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Darius Dabir
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Daniel Thomas
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Jonel Trebicka
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Ulrike Attenberger
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Daniel Kuetting
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
| | - Julian A Luetkens
- From the Departments of Radiology (A.I., A.F., A.M.S., C.C.P., C.M., D.D., D.T., U.A., D.K., J.A.L.) and Internal Medicine I (M.P., C.J., J.C.), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Quantitative Imaging Laboratory Bonn (QILaB), Bonn, Germany (A.I., A.F., A.M.S., D.D., D.T., D.K., J.A.L.); Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany (R.F.); Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany (J.T.)
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Arya S, Deshpande H, Belwal S, Sharma P, Sadana P, Chandrakant, Rahman F, Gupta M, Uniyal B. Association between cardiac dysfunction, arrhythmias and chronic liver diseases: A narrative review. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2020. [DOI: 10.1016/j.tacc.2020.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Han H, Qin Y, Yu Y, Wei X, Guo H, Ruan Y, Cao Y, He J. Atrial fibrillation in hospitalized patients with end-stage liver disease: temporal trends in prevalence and outcomes. Liver Int 2020; 40:674-684. [PMID: 31705572 DOI: 10.1111/liv.14291] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 10/29/2019] [Accepted: 10/31/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS End-stage liver disease (ESLD) happens due to the development and progression of chronic liver disease. This study aims to investigate the temporal trend, patient characteristics and outcomes of atrial fibrillation (AF) in hospitalized ESLD patients across the United States. METHODS Nationwide Inpatient Sample from 2003 to 2014 was utilized to retrospectively study the weighted prevalence of AF in hospitalized ESLD patients. Multivariable regression models were used to assess the association between AF with clinical factors, in-hospital mortality, length of stay (LOS) and cost. RESULTS 639 345 hospitalizations associated with ESLD were identified, of which 47 710 (7.48%) were diagnosed with AF. The prevalence of AF increased from 5.73% in 2003 to 9.75% in 2014 in ESLD and varied by age, race, income, insurance type and hospital characteristics. Factors associated with AF included advancing age, male, white race, high income and urban teaching hospital. AF presence was associated with significant higher in-hospital mortality (odds ratio, 1.40; 95% confidence interval, 1.35-1.45), 21% longer LOS and 22% higher cost. In addition, a significant decreasing trend in in-hospital mortality was observed (from 16.70% to 10.63% in patients with AF and from 10.74% to 7.50% in patients without AF). CONCLUSIONS The prevalence of AF in hospitalized ESLD patients has continued to increase from 2003 through 2014. AF is associated with poor prognosis and higher health resource utilization. Innovative anticoagulation strategies through improved collaboration between cardiologists and hepatologists are required for better management of hospitalized ESLD patients comorbid with AF.
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Affiliation(s)
- Hedong Han
- Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Yingyi Qin
- Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Yamei Yu
- Department of Cardiology, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xin Wei
- Department of Cardiology, Virginia Commonwealth University, Richmond, VA, USA
| | - Honglei Guo
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yiming Ruan
- Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Yang Cao
- Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Jia He
- Department of Health Statistics, Second Military Medical University, Shanghai, China.,Tongji University School of Medicine, Shanghai, China
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El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Relationship between Heart Disease and Liver Disease: A Two-Way Street. Cells 2020; 9:cells9030567. [PMID: 32121065 PMCID: PMC7140474 DOI: 10.3390/cells9030567] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/23/2020] [Accepted: 02/25/2020] [Indexed: 12/18/2022] Open
Abstract
In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation.
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Affiliation(s)
- Hamza El Hadi
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
- Department of Medicine, Klinikum Rheine, 48431 Rheine, Germany
| | - Angelo Di Vincenzo
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
| | - Marco Rossato
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
- Correspondence: ; Tel.: +39-049-8218747; Fax: +39049-8213332
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Chokesuwattanaskul R, Thongprayoon C, Bathini T, O'Corragain OA, Sharma K, Preechawat S, Wijarnpreecha K, Kröner PT, Ungprasert P, Cheungpasitporn W. Epidemiology of atrial fibrillation in patients with cirrhosis and clinical significance: a meta-analysis. Eur J Gastroenterol Hepatol 2019; 31:514-519. [PMID: 30451705 DOI: 10.1097/meg.0000000000001315] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The epidemiology of atrial fibrillation (AF) in patients with cirrhosis and its clinical significance remain unclear. This study aimed (i) to investigate the pooled prevalence and/or incidence of AF in patients with cirrhosis and (ii) to assess the mortality risk of AF in patients with cirrhosis. PATIENTS AND METHODS A literature search for studies that reported incidence of AF in patients with cirrhosis was carried out using Medline, Embase, and Cochrane Database from inception through July 2018. Pooled incidence with 95% confidence interval (CI) was calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018102664). RESULTS Seven cohort studies including 385 866 patients with cirrhosis were identified. The pooled estimated prevalence of AF in patients with cirrhosis was 5.0% (95% CI: 2.8-8.6%). When studies that solely assessed patients undergoing transplant evaluation or on transplant waiting list were excluded, the pooled estimated prevalence of AF in patients with cirrhosis was 7.4% (95% CI: 3.5-15.2%). There was a significant association between AF and increased mortality risk in cirrhotic patients with a pooled odds ratio of 1.44 (95% CI: 1.36-1.53). CONCLUSION The overall estimated prevalence of AF among patients with cirrhosis is 5.0%. Our study demonstrates a statistically significant increased mortality risk in cirrhotic patients with AF.
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Affiliation(s)
- Ronpichai Chokesuwattanaskul
- Department of Medicine, Division of Cardiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | | | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, Arizona
| | - Oisin A O'Corragain
- Department of Internal Medicine, Temple University Hospital, Philadelphia, Pennsylvania
| | - Konika Sharma
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York
| | - Somchai Preechawat
- Department of Medicine, Division of Cardiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | | | - Paul T Kröner
- Division of Gastroenterology, Mayo Clinic, Jacksonville, Florida
| | - Patompong Ungprasert
- Department of Research and Development, Clinical Epidemiology Unit, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Carvalho MVH, Kroll PC, Kroll RTM, Carvalho VN. Cirrhotic cardiomyopathy: the liver affects the heart. ACTA ACUST UNITED AC 2019; 52:e7809. [PMID: 30785477 PMCID: PMC6376321 DOI: 10.1590/1414-431x20187809] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 12/04/2018] [Indexed: 12/14/2022]
Abstract
Cirrhotic cardiomyopathy historically has been confused as alcoholic cardiomyopathy. The key points for diagnosis of cirrhotic cardiomyopathy have been well explained, however this entity was neglected for a long time. Nowadays the diagnosis of this entity has become important because it is a factor that contributes significantly to morbidity-mortality in cirrhotic patients. Characteristics of cirrhotic cardiomyopathy are a hyperdynamic circulatory state, altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, particularity QT interval prolongation. The pathogenesis includes impaired function of beta-receptors, altered transmembrane currents and overproduction of cardiodepressant factors, such as nitric oxide, cytokines and endogenous cannabinoids. In addition to physical signs of hyperdynamic state and heart failure under stress conditions, the diagnosis can be done with dosage of serum markers, electrocardiography, echocardiography and magnetic resonance. The treatment is mainly supportive, but orthotopic liver transplantation appears to improve this condition although the prognosis of liver transplantation in patients with cirrhotic cardiomyopathy is uncertain.
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Affiliation(s)
- M V H Carvalho
- Departamento de Cirurgia, Faculdade de Medicina de Jundiaí, Jundiaí, SP, Brasil
| | - P C Kroll
- Hospital de Transplante E.J. Zerbini, São Paulo, SP, Brasil
| | - R T M Kroll
- Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, Brasil
| | - V N Carvalho
- Hospital Municipal Dr. Mario Gatti, Campinas, SP, Brasil
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Ashmawy MM, Younis HA, Elbaset MAA, Rahman HAA, Ashmawy AM, Shawky MAEG, Elnasser MMA. Evaluation of cardiac function in patients with liver cirrhosis using tissue Doppler study. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2018. [DOI: 10.4103/ejim.ejim_28_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Snipelisky D, Shipman J, Olson N, Pellikka P, Aqel B, McCully R, Watt K. Low to Intermediate Dose Atropine Administration During Dobutamine Stress Echocardiography in the Pre-Liver Transplant Population. Prog Transplant 2018; 28:361-367. [PMID: 30222085 DOI: 10.1177/1526924818800048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD). RESEARCH QUESTION What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing? DESIGN This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none. RESULTS Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing. CONCLUSIONS Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.
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Affiliation(s)
- David Snipelisky
- 1 Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Justin Shipman
- 2 Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ, USA
| | - Nicole Olson
- 3 Department of Pharmacy, Mayo Clinic, Rochester, MN, USA
| | - Patricia Pellikka
- 1 Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Bashar Aqel
- 4 Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Robert McCully
- 1 Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Kymberly Watt
- 5 Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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Abstract
BACKGROUND Cirrhotic cardiomyopathy is characterized by an attenuated contractile response to stress. Long-term exposure of β-adrenergic receptors to persistently high levels of catecholamines has been implicated in its pathogenesis. We hypothesized that β-blockade with metoprolol could reverse the changes in heart function and morphology in cirrhotic cardiomyopathy. PATIENTS AND METHODS In this prospective randomized trial, we included 78 patients aged between 18 and 60 years with abnormal cardiac output response under dobutamine stress echocardiography, without primary cardiac disease or a history of alcohol intake. Patients were assigned randomly to receive metoprolol or placebo for 6 months. The primary endpoint was the improvement in cardiac output response to stress, measured by an increase in the left ventricle stroke volume more than 30%. RESULTS Three (7.3%) patients in the metoprolol group and nine (24.3%) patients in the placebo group showed improved stroke volume (P=0.057). Diastolic dysfunction was found in two (4.8%) patients before and in five (15.6%) patients after therapy in the metoprolol group, and in 10 (27%) patients before and nine (31%) patients after therapy in the placebo group (P=0.67). After treatment, no echocardiography parameter of morphology was significantly different between metoprolol or placebo groups. No significant differences were observed in noradrenaline, plasma renin activity, and troponin levels between groups. Cirrhosis-related clinical events, including hospitalizations and mortality, were not significantly different between the two groups. Six months of therapy with β-blocker did not ameliorate heart function and morphology in patients with cirrhotic cardiomyopathy.
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Sharma S, Karamchandani K, Wilson R, Baskin S, Bezinover D. Acute heart failure after Orthotopic liver transplantation: a case series from one center. BMC Anesthesiol 2018; 18:102. [PMID: 30064379 PMCID: PMC6069825 DOI: 10.1186/s12871-018-0560-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 07/17/2018] [Indexed: 01/09/2023] Open
Abstract
Background Patients undergoing liver transplantation (LT) can develop acute heart failure (HF) in the postoperative period despite having had a normal cardiac evaluation prior to surgery. End-stage liver disease is often associated with underlying cardiac dysfunction which, while not identified during preoperative testing, manifests itself during or immediately after surgery. Case presentation We describe three cases of non-ischemic acute HF developing shortly after LT in patients who had a normal preoperative cardiac evaluation. The challenges associated with both diagnosis and management of acute HF in the setting of a newly implanted graft will be discussed. Conclusions Diastolic dysfunction, QTc interval prolongation, and an increase in BNP may be predictive of postoperative HF. Current recommendations for preoperative cardiovascular evaluation of transplant candidates does not include studies examining these risk factors and should be revised. Further investigations are necessary to evaluate these findings.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine/ Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H187, P.O. Box 850, Hershey, PA, 17033-0850, USA
| | - Kunal Karamchandani
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine/ Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H187, P.O. Box 850, Hershey, PA, 17033-0850, USA
| | - Ryan Wilson
- Department of Cardiology, Penn State College of Medicine/ Penn State Health Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA
| | - Sean Baskin
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine/ Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H187, P.O. Box 850, Hershey, PA, 17033-0850, USA
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine/ Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H187, P.O. Box 850, Hershey, PA, 17033-0850, USA.
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Gitman M, Albertz M, Nicolau-Raducu R, Aniskevich S, Pai SL. Cardiac diseases among liver transplant candidates. Clin Transplant 2018; 32:e13296. [PMID: 29804298 DOI: 10.1111/ctr.13296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2018] [Indexed: 11/29/2022]
Abstract
Improvements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post-LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. As no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work-up.
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Affiliation(s)
- Marina Gitman
- Department of Anesthesiology, University of Illinois Hospital, Chicago, IL, USA
| | - Megan Albertz
- Department of Anesthesiology, Children's Hospital Colorado, Aurora, CO, USA
| | | | - Stephen Aniskevich
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Sher-Lu Pai
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
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Jansen C, Al-Kassou B, Lehmann J, Pohlmann A, Chang J, Praktiknjo M, Nickenig G, Strassburg CP, Schrickel JW, Andrié R, Linhart M, Trebicka J. Severe abnormal Heart Rate Turbulence Onset is associated with deterioration of liver cirrhosis. PLoS One 2018; 13:e0195631. [PMID: 29634776 PMCID: PMC5892926 DOI: 10.1371/journal.pone.0195631] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023] Open
Abstract
Background In patients with liver cirrhosis, cardiac dysfunction is frequent and is associated with increased morbidity and mortality. Cardiac dysfunction in cirrhosis seems to be linked to autonomic dysfunction. This study investigates the role of autonomic dysfunction assessed by Heart Rate Turbulence (HRT) analyses in patients with liver cirrhosis. Methods and patients Inclusion criteria was (1) diagnosis of cirrhosis by clinical, imaging or biopsy and (2) evaluation by standard 12-lead-ECG and 24h holter monitoring and (3) at least 3 premature ventricular contractions. The exclusion criterion was presence of cardiac diseases, independent of liver cirrhosis. Biochemical parameters were analysed using standard methods. HRT was assessed using Turbulence onset (TO) and slope (TS). The endpoint was deterioration of liver cirrhosis defined as increased MELD and readmission for complications of liver cirrhosis. Results Out of 122 cirrhotic patients, 82 patients (63% male) with median Child score of 6 (range 5–12) and median MELD score of 10 (range 6–32) were included. Increasing Child score, INR and decreasing albumin were correlated with TO. In addition, decompensated patients with ascites showed more abnormal TO and TS. During the observation period, patients with more abnormal TO showed significantly higher rate of rising MELD Score at 6 months (p = 0.03). Nevertheless, at least in our collective HRT-parameters were not independent predictors of deterioration of cirrhosis. Conclusion Parameters of HRT are closely associated with deterioration of cirrhosis and might be helpful in its prediction.
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Affiliation(s)
- Christian Jansen
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Baravan Al-Kassou
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jennifer Lehmann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Johannes Chang
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Georg Nickenig
- Department of Internal Medicine II, University of Bonn, Bonn, Germany
| | | | - Jan W. Schrickel
- Department of Internal Medicine II, University of Bonn, Bonn, Germany
| | - René Andrié
- Department of Internal Medicine II, University of Bonn, Bonn, Germany
| | - Markus Linhart
- Department of Internal Medicine II, University of Bonn, Bonn, Germany
- Cardiology Department, Hospital Clínic, Barcelona, Spain
| | - Jonel Trebicka
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
- Institute for Bioengineering of Catalonia, Barcelona, Spain
- * E-mail:
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Abstract
Anesthesia for liver transplantation pertains to a continuum of critical care of patients with end-stage liver disease. Hence, anesthesiologists, armed with a comprehensive understanding of pathophysiology and physiologic effects of liver transplantation on recipients, are expected to maintain homeostasis of all organ function. Specifically, patients with fulminant hepatic failure develop significant changes in cerebral function, and cerebral perfusion is maintained by monitoring cerebral blood flow and cerebral metabolic rate of oxygen, and intracranial pressure. Hyperdynamic circulation is challenged by the postreperfusion syndrome, which may lead to cardiovascular collapse. The goal of circulatory support is to maintain tissue perfusion via optimal preload, contractility, and heart rate using the guidance of right-heart catheterization and transesophageal echocardiography. Portopulmonary hypertension and hepatopulmonary syndrome have high morbidity and mortality, and they should be properly evaluated preoperatively. Major bleeding is a common occurrence, and euvolemia is maintained using a rapid infusion device. Pre-existing coagulopathy is compounded by dilution, fibrinolysis, heparin effect, and excessive activation. It is treated using selective component or pharmacologic therapy based on the viscoelastic properties of whole blood. Hypocalcemia and hyperkalemia from massive transfusion, lack of hepatic function, and the postreperfusion syndrome should be aggressively treated. Close communication between all parties involved in liver transplantation is also equally valuable in achieving a successful outcome.
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Abstract
Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
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Affiliation(s)
| | - Suthat Liangpunsakul
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Hospital, 550 University Boulevard, UH 4100, Indianapolis, IN 46202-5149, USA; Roudebush Veterans Administration Medical Center, Indiana University, Indianapolis, IN, USA
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Abstract
Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
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Affiliation(s)
| | - Suthat Liangpunsakul
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Hospital, 550 University Boulevard, UH 4100, Indianapolis, IN 46202-5149, USA; Roudebush Veterans Administration Medical Center, Indiana University, Indianapolis, IN, USA
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Sampaio F, Lamata P, Bettencourt N, Alt SC, Ferreira N, Kowallick JT, Pimenta J, Kutty S, Fraga J, Steinmetz M, Bettencourt P, Gama V, Schuster A. Assessment of cardiovascular physiology using dobutamine stress cardiovascular magnetic resonance reveals impaired contractile reserve in patients with cirrhotic cardiomyopathy. J Cardiovasc Magn Reson 2015; 17:61. [PMID: 26187817 PMCID: PMC4506630 DOI: 10.1186/s12968-015-0157-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 06/22/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cirrhosis has been shown to affect cardiac performance. However cardiac dysfunction may only be revealed under stress conditions. The value of non-invasive stress tests in diagnosing cirrhotic cardiomyopathy is unclear. We sought to investigate the response to pharmacological stimulation with dobutamine in patients with cirrhosis using cardiovascular magnetic resonance. METHODS Thirty-six patients and eight controls were scanned using a 1.5 T scanner (Siemens Symphony TIM; Siemens, Erlangen, Germany). Conventional volumetric and feature tracking analysis using dedicated software (CMR42; Circle Cardiovascular Imaging Inc, Calgary, Canada and Diogenes MRI; Tomtec; Germany, respectively) were performed at rest and during low to intermediate dose dobutamine stress. RESULTS Whilst volumetry based parameters were similar between patients and controls at rest, patients had a smaller increase in cardiac output during stress (p = 0.015). Ejection fraction increase was impaired in patients during 10 μg/kg/min dobutamine as compared to controls (6.9 % vs. 16.5 %, p = 0.007), but not with 20 μg/kg/min (12.1 % vs. 17.6 %, p = 0.12). This was paralleled by an impaired improvement in circumferential strain with low dose (median increase of 14.4 % vs. 30.9 %, p = 0.03), but not with intermediate dose dobutamine (median increase of 29.4 % vs. 33.9 %, p = 0.54). There was an impaired longitudinal strain increase in patients as compared to controls during low (median increase of 6.6 % vs 28.6 %, p < 0.001) and intermediate dose dobutamine (median increase of 2.6%vs, 12.6 % p = 0.016). Radial strain response to dobutamine was similar in patients and controls (p > 0.05). CONCLUSION Cirrhotic cardiomyopathy is characterized by an impaired cardiac pharmacological response that can be detected with magnetic resonance myocardial stress testing. Deformation analysis parameters may be more sensitive in identifying abnormalities in inotropic response to stress than conventional methods.
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MESH Headings
- Aged
- Cardiomyopathies/diagnosis
- Cardiomyopathies/etiology
- Cardiomyopathies/physiopathology
- Cardiotonic Agents/administration & dosage
- Case-Control Studies
- Dobutamine/administration & dosage
- Female
- Humans
- Image Interpretation, Computer-Assisted
- Liver Cirrhosis/complications
- Liver Cirrhosis/diagnosis
- Magnetic Resonance Imaging, Cine/methods
- Male
- Middle Aged
- Myocardial Contraction
- Observer Variation
- Predictive Value of Tests
- Reproducibility of Results
- Software
- Stroke Volume
- Ventricular Dysfunction, Left/diagnosis
- Ventricular Dysfunction, Left/etiology
- Ventricular Dysfunction, Left/physiopathology
- Ventricular Dysfunction, Right/diagnosis
- Ventricular Dysfunction, Right/etiology
- Ventricular Dysfunction, Right/physiopathology
- Ventricular Function, Left
- Ventricular Function, Right
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Affiliation(s)
- Francisco Sampaio
- Cardiology Department, Centro Hospitalar de Gaia/Espinho, Rua Conceição Fernandes, 4430-502 Vila Nova de Gaia, Espinho, Portugal.
- University of Porto Medical School, Porto, Portugal.
| | - Pablo Lamata
- Division of Imaging Sciences and Biomedical Engineering, The Rayne Institute, Kings College London, St. Thomas' Hospital, London, UK.
| | - Nuno Bettencourt
- Cardiology Department, Centro Hospitalar de Gaia/Espinho, Rua Conceição Fernandes, 4430-502 Vila Nova de Gaia, Espinho, Portugal.
- University of Porto Medical School, Porto, Portugal.
| | - Sophie Charlotte Alt
- Department of Pediatric Cardiology and Intensive Care Medicine, Georg-August University, Göttingen, Germany.
| | - Nuno Ferreira
- Cardiology Department, Centro Hospitalar de Gaia/Espinho, Rua Conceição Fernandes, 4430-502 Vila Nova de Gaia, Espinho, Portugal.
| | - Johannes Tammo Kowallick
- Institute for Diagnostic and Interventional Radiology, Georg-August University, Göttingen, Germany.
- DZHK (German Centre for Cardiovascular Research), Göttingen, Germany.
| | - Joana Pimenta
- University of Porto Medical School, Porto, Portugal.
| | - Shelby Kutty
- University of Nebraska Medical Center/ Children's Hospital and Medical Center, Omaha, NE, USA.
| | - José Fraga
- Gastroenterology Department, Centro Hospitalar de Gaia/Espinho, Espinho, Portugal.
| | - Michael Steinmetz
- Department of Pediatric Cardiology and Intensive Care Medicine, Georg-August University, Göttingen, Germany.
- DZHK (German Centre for Cardiovascular Research), Göttingen, Germany.
| | | | - Vasco Gama
- Cardiology Department, Centro Hospitalar de Gaia/Espinho, Rua Conceição Fernandes, 4430-502 Vila Nova de Gaia, Espinho, Portugal.
| | - Andreas Schuster
- Division of Imaging Sciences and Biomedical Engineering, The Rayne Institute, Kings College London, St. Thomas' Hospital, London, UK.
- DZHK (German Centre for Cardiovascular Research), Göttingen, Germany.
- Department of Cardiology and Pneumology, Georg-August University, Göttingen, Germany.
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Karagiannakis DS, Papatheodoridis G, Vlachogiannakos J. Recent advances in cirrhotic cardiomyopathy. Dig Dis Sci 2015; 60:1141-1151. [PMID: 25404411 DOI: 10.1007/s10620-014-3432-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 11/08/2014] [Indexed: 12/15/2022]
Abstract
Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.
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Affiliation(s)
- Dimitrios S Karagiannakis
- Department of Gastroenterology, Medical School of Athens University, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece,
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41
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Prin M, Bakker J, Wagener G. Hepatosplanchnic circulation in cirrhosis and sepsis. World J Gastroenterol 2015; 21:2582-2592. [PMID: 25759525 PMCID: PMC4351207 DOI: 10.3748/wjg.v21.i9.2582] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Revised: 11/15/2014] [Accepted: 01/21/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage. Sepsis and cirrhosis result in similar circulatory changes and resultant multi-organ dysfunction. This review provides an overview of the hepatosplanchnic circulation in the healthy state and in cirrhosis, examines the signaling pathways that may play a role in the physiology of cirrhosis, discusses the physiology common to cirrhosis and sepsis, and reviews important issues in management.
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42
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Gassanov N, Caglayan E, Semmo N, Massenkeil G, Er F. Cirrhotic cardiomyopathy: A cardiologist’s perspective. World J Gastroenterol 2014; 20:15492-15498. [PMID: 25400434 PMCID: PMC4229515 DOI: 10.3748/wjg.v20.i42.15492] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 04/01/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy (CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricular relaxation and ventricular filling is a prominent feature of CCM. The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy, fibrosis and subendothelial edema, subsequently resulting in high filling pressures of the left ventricle and atrium. Currently, no specific treatment exists for CCM. The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure. Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation. Here, we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy, and discuss currently available limited therapeutic options.
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Krag A, Bendtsen F, Dahl EK, Kjær A, Petersen CL, Møller S. Cardiac function in patients with early cirrhosis during maximal beta-adrenergic drive: a dobutamine stress study. PLoS One 2014; 9:e109179. [PMID: 25279659 PMCID: PMC4184863 DOI: 10.1371/journal.pone.0109179] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 09/10/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIM Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis. PATIENTS AND METHODS Nineteen patients with Child A and B cirrhosis (9 with non-alcoholic cirrhosis) and 7 matched controls were included. We used cardiac magnetic resonance imaging to assess left ventricular volumes and cardiac output (CO) at rest and during maximal heart rate induced by increasing dosages of dobutamine and atropine. RESULTS Patients with cirrhosis and controls had an equal stress response, the heart rate and ejection fraction increased similarly and maximal heart rate was reached in all. At rest CO was higher in Child B patients than controls. During maximal stress, Child B patients had higher CO (10.6±2.7 vs. 8.0±1.8 L/min), left ventricle end diastolic volume (90±25 vs. 67±16 mL), left ventricular end diastolic volume (10±4 vs. 6±2 mL) and stroke volume (80±23 vs. 61±15 mL) than Child A patients. The systemic vascular resistance was lower in Child B than Child A patients (670±279 vs. 911±274 dyne*s*cm(-5)). The left ventricle mass increased by 5.6 gram per model for end stage liver disease (MELD) point. MELD score correlated with the end diastolic and systolic volume, CO, and stroke volume at rest and at stress (all p<0.05). CONCLUSION In patients with early cirrhosis the chronotropoic and inotropic response to pharmacological stress induced by dobutamine is normal. With progression of the disease, the mass of the heart increases along with increase in cardiac volumes.
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Affiliation(s)
- Aleksander Krag
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Andreas Kjær
- Hvidovre Hospital, Department of Clinical Physiology Nuclear Medicine & PET, Rigshospitalet, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Claus Leth Petersen
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
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Abstract
With the incidence of liver disease increasing worldwide, a growing number of patients are being referred for assessment for liver transplant (LT). Unfortunately, the donor pool is not expanding at the same rate, which consequentially results in increasing demand on a finite resource. It is therefore imperative that the candidate who undergoes an LT gets maximal benefit with a resultant maximal increase in life expectancy. This article addresses some of the main cardiac and pulmonary issues that may occur in LT assessment candidates.
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Affiliation(s)
- Norma C McAvoy
- Department of Hepatology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, Great Britain
| | - Peter C Hayes
- Department of Hepatology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, Great Britain.
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45
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Bolognesi M, Di Pascoli M, Verardo A, Gatta A. Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis. World J Gastroenterol 2014; 20:2555-2563. [PMID: 24627591 PMCID: PMC3949264 DOI: 10.3748/wjg.v20.i10.2555] [Citation(s) in RCA: 147] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Revised: 11/08/2013] [Accepted: 11/30/2013] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension is a clinical syndrome which leads to several clinical complications, such as the formation and rupture of esophageal and/or gastric varices, ascites, hepatic encephalopathy and hepato-renal syndrome. In cirrhosis, the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow. However, also an increase in splanchnic blood flow worsens and maintains portal hypertension. The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow. Several vasoactive systems/substances, such as nitric oxide, cyclooxygenase-derivatives, carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation. Moreover, an impaired reactivity to vasoconstrictor systems, such as the sympathetic nervous system, vasopressin, angiotensin II and endothelin-1, plays a role in this process. The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels, but also through the generation of new vessels. Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome, a syndrome which occurs in patients with portal hypertension and is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure. Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.
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46
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Wiese S, Hove JD, Bendtsen F, Møller S. Cirrhotic cardiomyopathy: pathogenesis and clinical relevance. Nat Rev Gastroenterol Hepatol 2014; 11:177-86. [PMID: 24217347 DOI: 10.1038/nrgastro.2013.210] [Citation(s) in RCA: 168] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cirrhosis is known to cause alterations in the systemic haemodynamic system. Cirrhotic cardiomyopathy designates a cardiac dysfunction that includes impaired cardiac contractility with systolic and diastolic dysfunction, as well as electromechanical abnormalities in the absence of other known causes of cardiac disease. This condition is primarily revealed by inducing physical or pharmacological stress, but echocardiography is excellent at revealing diastolic dysfunction and might also be used to detect systolic dysfunction at rest. Furthermore, measurement of circulating levels of cardiac biomarkers could improve the diagnostic assessm+ent. Cirrhotic cardiomyopathy contributes to various complications in cirrhosis, especially as an important factor in the development of hepatic nephropathy. Additionally, cirrhotic cardiomyopathy seems to be associated with the development of heart failure in relation to invasive procedures such as shunt insertion and liver transplantation. Current pharmacological treatment is nonspecific and directed towards left ventricular failure, and liver transplantation is currently the only proven treatment with specific effect on cirrhotic cardiomyopathy.
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Affiliation(s)
- Signe Wiese
- Centre for Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark
| | - Jens D Hove
- Department of Cardiology, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastroenterology Unit, Medical Division, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark
| | - Søren Møller
- Centre for Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark
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47
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New insights into cirrhotic cardiomyopathy. Int J Cardiol 2013; 167:1101-8. [DOI: 10.1016/j.ijcard.2012.09.089] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 07/02/2012] [Accepted: 09/15/2012] [Indexed: 02/06/2023]
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48
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Polavarapu N, Tripathi D. Liver in cardiopulmonary disease. Best Pract Res Clin Gastroenterol 2013; 27:497-512. [PMID: 24090938 DOI: 10.1016/j.bpg.2013.06.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Accepted: 06/12/2013] [Indexed: 01/31/2023]
Abstract
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) are two fascinating and incompletely understood pulmonary vascular conditions seen in the setting of cirrhotic patients. Of the two HPS is more common and is primarily caused by pulmonary vasodilatation resulting in hypoxaemia and hyperdynamic circulation. PoPH is less common and conversely, pulmonary vasoconstriction and vascular remodelling occurs resulting in increased pulmonary vascular resistance. However, both conditions can co-exist and it is usually PoPH which develops in a patient with pre-existing HPS. Although these two pulmonary conditions are not common complications of chronic liver diseases, the treatment options are mainly limited to liver transplantation. Cirrhotic cardiomyopathy is closely related to haemodynamic changes in portal hypertension. The key features are normal cardiac pressures at rest, with reduced ability to compensate for physiological or iatrogenic stresses such as drug therapy or TIPSS. There is no effective therapy and outcomes after liver transplantation are variable.
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Affiliation(s)
- Naveen Polavarapu
- Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham B15 2TH, UK
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HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats without major systemic effects. J Hepatol 2012; 57:1220-7. [PMID: 22878469 DOI: 10.1016/j.jhep.2012.07.033] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2012] [Revised: 07/24/2012] [Accepted: 07/27/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Rho-kinase activation mediates cell contraction and increases intrahepatic resistance and consequently portal pressure in liver cirrhosis. Systemic Rho-kinase inhibition decreases portal pressure in cirrhosis, but also arterial pressure. Thus, liver-specific Rho-kinase inhibition is needed. The delivery of Rho-kinase inhibitor to activated hepatic stellate cells reduces fibrosis. It might also relax these contractile cells and therewith decrease intrahepatic resistance. We tested this hypothesis by performing acute experiments in cirrhotic rats. METHODS Cirrhosis models were CCl(4)-intoxication and bile duct ligation. Three hours after injection of the Rho-kinase inhibitor (Y26732) coupled with a carrier (mannose-6-phosphate modified human serum albumin), which targets activated hepatic stellate cells, hemodynamics were analyzed by the colored microsphere technique and direct pressure measurements. The delivery site and effect of Rho-kinase inhibitor were investigated by immunohistochemical stainings, as well as Western blot. Experiments with Rho-kinase inhibitor coupled with unmodified human serum albumin served as untargeted control. RESULTS In both models of cirrhosis, the carrier coupled Rho-kinase inhibitor lowered the portal pressure and decreased the hepatic-portal resistance. Immunohistochemical desmin-staining showed the carrier in hepatic stellate cells. The targeted therapy decreased the expression of the phosphorylated substrate of Rho-kinase (moesin) and abolished myosin light chains phosphorylation in fibrotic septae (collagen-staining). The targeted Rho-kinase inhibitor showed no major extrahepatic effects. By contrast, the untargeted Rho-kinase inhibitor elicited severe systemic hypotension. CONCLUSIONS Activated hepatic stellate cells are crucially involved in portal hypertension in cirrhosis. Targeting of Rho-kinase in hepatic stellate cells not only decreased fibrosis, as previously shown, but also lowers portal pressure acutely without major systemic effects as demonstrated in this study.
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50
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Møller S, Mortensen C, Bendtsen F, Jensen LT, Gøtze JP, Madsen JL. Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function. Am J Physiol Gastrointest Liver Physiol 2012; 303:G1228-35. [PMID: 23019196 DOI: 10.1152/ajpgi.00303.2012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake, and in patients with cardiac failure it predicts outcome. In this study, we aimed to investigate cardiac sympathetic neuronal function in cirrhosis by mIBG scintigraphy in relation to cardiovascular function. Ten patients with alcoholic cirrhosis and 10 age- and sex-matched healthy controls participated in the study. Heart/mediastinum (H/M) ratios of mIBG uptake were calculated 15 and 230 min after intravenous injection of mIBG. Furthermore, washout rate (WOR) of mIBG was calculated. The patients underwent a liver vein catheterization with determination of splanchnic and systemic hemodynamics and measurement of HRV and BRS. mIBG-scintigraphy revealed significantly increased WOR in patients with cirrhosis compared with controls (P < 0.005), whereas H/M uptakes were equal in the groups. Forty percent of the patients had reduced uptake of mIBG in the infero-lateral segment of the left ventricle. WOR correlated significantly with central circulation time, an estimate of central hypovolemia (r = -0.64, P < 0.05) and frequency-corrected QT(F) interval (r = 0.71, P = 0.01). Patients with cirrhosis had significantly decreased HRV and BRS correlating with indicators of abnormal cathecholamine uptake by mIBG although the catecholamine level was normal in the patients. In conclusion, in alcoholic cirrhosis, mIBG scintigraphy reveals autonomic dysfunction and impaired myocardial distribution of sympathetic nervous activity. It is associated to indicators of central hypovolemia, QT interval, and decreased HRV and BRS. Measurement of myocardial catecholamine uptake by mIBG may add important information on autonomic and cardiac dysfunction in cirrhosis.
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Affiliation(s)
- Søren Møller
- Center. of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Kettegaard Alle 30, DK-2650 Hvidovre, Copenhagen, Denmark.
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