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Papadopoulos VP, Mimidis K. Corrected QT interval in cirrhosis: A systematic review and meta-analysis. World J Hepatol 2023; 15:1060-1083. [PMID: 37900213 PMCID: PMC10600695 DOI: 10.4254/wjh.v15.i9.1060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 08/13/2023] [Accepted: 08/29/2023] [Indexed: 09/22/2023] Open
Abstract
BACKGROUND Corrected QT (QTc) interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease. However, the effects of sex, age, severity, and etiology of cirrhosis on QTc have not been elucidated. At the same time, the role of treatment, acute illness, and liver transplantation (Tx) remains largely unknown. AIM To determine the mean QTc in patients with cirrhosis, assess whether QTc is prolonged in patients with cirrhosis, and investigate whether QTc is affected by factors such as sex, age, severity, etiology, treatment, acute illness, and liver Tx. METHODS In the present systematic review and meta-analysis, the searching protocol "{[QTc] OR [QT interval] OR [QT-interval] OR [Q-T syndrome]} AND {[cirrhosis] OR [Child-Pugh] OR [MELD]}" was applied in PubMed, EMBASE, and Google Scholar databases to identify studies that reported QTc in patients with cirrhosis and published after 1998. Seventy-three studies were considered eligible. Data concerning first author, year of publication, type of study, method used, sample size, mean age, female ratio, alcoholic etiology of cirrhosis ratio, Child-Pugh A/B/C ratio, mean model for end-stage liver disease (MELD) score, treatment with β-blockers, episode of acute gastrointestinal bleeding, formula for QT correction, mean pulse rate, QTc in patients with cirrhosis and controls, and QTc according to etiology of cirrhosis, sex, Child-Pugh stage, MELD score, and liver Tx status (pre-Tx/post-Tx) were retrieved. The Newcastle-Ottawa quality assessment scale appraised the quality of the eligible studies. Effect estimates, expressed as proportions or standardized mean differences, were combined using the random-effects, generic inverse variance method of DerSimonian and Laird. Subgroup, sensitivity analysis, and meta-regressions were applied to assess heterogeneity. The study has been registered in the PROSPERO database (CRD42023416595). RESULTS QTc combined mean in patients with cirrhosis was 444.8 ms [95% confidence interval (CI): 440.4-449.2; P < 0.001 when compared with the upper normal limit of 440 ms], presenting high heterogeneity (I2 = 97.5%; 95%CI: 97.2%-97.8%); both Egger's and Begg's tests showed non-significance. QTc was elongated in patients with cirrhosis compared with controls (P < 0.001). QTc was longer in patients with Child-Pugh C cirrhosis when compared with Child-Pugh B and A (P < 0.001); Child-Pugh B patients presented longer QTc when compared with Child-Pugh A patients (P = 0.003). The MELD score was higher in patients with cirrhosis with QTc > 440 ms when compared with QTc ≤ 440 ms (P < 0.001). No correlation of QTc with age (P = 0.693), sex (P = 0.753), or etiology (P = 0.418) was detected. β-blockers shortened QTc (P< 0.001). QTc was prolonged during acute gastrointestinal bleeding (P = 0.020). Tx tended to improve QTc (P < 0.001). No other sources of QTc heterogeneity were revealed. CONCLUSION QTc is prolonged in cirrhosis independently of sex, age, and etiology but is correlated with severity and affected by β-blockers and acute gastrointestinal bleeding. QTc is improved after liver Tx.
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Affiliation(s)
| | - Konstantinos Mimidis
- First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis 68100, Greece
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2
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Isaak A, Chang J, Mesropyan N, Kravchenko D, Endler C, Bischoff L, Böhling N, Pieper CC, Kuetting D, Strassburg CP, Attenberger U, Jansen C, Praktiknjo M, Luetkens JA. Cardiac involvement in non-cirrhotic portal hypertension: MRI detects myocardial fibrosis and oedema similar to compensated cirrhosis. Eur Heart J Cardiovasc Imaging 2023; 24:949-960. [PMID: 36423215 DOI: 10.1093/ehjci/jeac235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 11/04/2022] [Indexed: 08/03/2023] Open
Abstract
AIMS The exact role of portal hypertension in cirrhotic cardiomyopathy remains unclear, and it is uncertain whether cardiac abnormalities also occur in non-cirrhotic portal hypertension (NCPH). This magnetic resonance imaging (MRI) study aimed to evaluate the presence of subclinical myocardial dysfunction, oedema, and fibrosis in NCPH. METHODS AND RESULTS In this prospective study (2018-2022), participants underwent multiparametric abdominal and cardiac MRI including assessment of cardiac function, myocardial oedema, late gadolinium enhancement (LGE), and abdominal and cardiac mapping [T1 and T2 relaxation times, extracellular volume fraction (ECV)]. A total of 111 participants were included [44 participants with NCPH (48 ± 15 years; 23 women), 47 cirrhotic controls, and 20 healthy controls]. The cirrhotic group was dichotomized (Child A vs. Child B/C). NCPH participants demonstrated a more hyperdynamic circulation compared with healthy controls (cardiac index: 3.7 ± 0.6 vs. 3.2 ± 0.8 L/min/m², P = 0.004; global longitudinal strain: -27.3 ± 4.6 vs. -24.6 ± 3.5%, P = 0.022). The extent of abnormalities indicating myocardial fibrosis and oedema in NCPH was comparable with Child A cirrhosis (e.g. LGE presence: 32 vs. 33 vs. 69%, P = 0.004; combined T1 and T2 elevations: 46 vs. 27 vs. 69%, P = 0.017; NCPH vs. Child A vs. Child B/C). Correlations between splenic T1 and myocardial T1 values were found (r = 0.41; P = 0.007). Splenic T1 values were associated with the presence of LGE (odds ratio, 1.010; 95% CI: 1.002, 1.019; P = 0.013). CONCLUSION MRI parameters of myocardial fibrosis and oedema were altered in participants with NCPH to a similar extent as in compensated cirrhosis and were associated with splenic markers of portal hypertension, indicating specific portal hypertensive cardiomyopathy.
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Affiliation(s)
- Alexander Isaak
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Johannes Chang
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Center for Cirrhosis and Portal Hypertension Bonn (CCB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Narine Mesropyan
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Dmitrij Kravchenko
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Christoph Endler
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Leon Bischoff
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Nina Böhling
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Center for Cirrhosis and Portal Hypertension Bonn (CCB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Claus C Pieper
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Daniel Kuetting
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Center for Cirrhosis and Portal Hypertension Bonn (CCB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Ulrike Attenberger
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Christian Jansen
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Center for Cirrhosis and Portal Hypertension Bonn (CCB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Michael Praktiknjo
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Center for Cirrhosis and Portal Hypertension Bonn (CCB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Julian A Luetkens
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Quantitative Imaging Lab Bonn (QILaB), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
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3
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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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Hemodynamic Evaluation of the Right Heart-Pulmonary Circulation Unit in Patients Candidate to Transjugular Intrahepatic Portosystemic Shunt. J Clin Med 2022; 11:jcm11020461. [PMID: 35054156 PMCID: PMC8778190 DOI: 10.3390/jcm11020461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/27/2021] [Accepted: 01/14/2022] [Indexed: 02/04/2023] Open
Abstract
In Europe, liver cirrhosis represents the fourth-most common cause of death, being responsible for 170,000 deaths and 5500 liver transplantations per year. The main driver of its decompensation is portal hypertension, whose progression radically changes the prognosis of affected patients. Transjugular intrahepatic portosystemic shunt (TIPS) is one of the main therapeutic strategies for these patients as it reverts portal hypertension, thus improving survival. However, the coexistence of portal hypertension and pulmonary hypertension or heart failure is considered a contraindication to TIPS. Nevertheless, in the latest guidelines, the definition of heart failure has not been specified. It is unclear whether the contraindication concerns the presence of clinical signs and symptoms of heart failure or hemodynamic changes in the right heart-pulmonary circulation. Moreover, data about induced right heart volume overload after TIPS and the potential development of heart failure and pulmonary hypertension is currently scanty and controversial. In this article we revise this issue in finding predictors of cardiac performance after TIPS procedure. Performing a fluid challenge during right heart catheterization might be a promising expedient to test the adaptation of the right ventricle to a sudden increase in preload in the first few months after TIPS. This test may unmask a potential cardiac inability to sustain the hemodynamic load after TIPS, allowing for a clearer definition of heart failure and, consequently, a more robust indication to TIPS.
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Zoratti C, Moretti R, Rebuzzi L, Albergati IV, Di Somma A, Decorti G, Di Bella S, Crocè LS, Giuffrè M. Antibiotics and Liver Cirrhosis: What the Physicians Need to Know. Antibiotics (Basel) 2021; 11:31. [PMID: 35052907 PMCID: PMC8772826 DOI: 10.3390/antibiotics11010031] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/13/2022] Open
Abstract
The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy.
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Affiliation(s)
- Caterina Zoratti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Lisa Rebuzzi
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Irma Valeria Albergati
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Antonietta Di Somma
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Giuliana Decorti
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy;
| | - Stefano Di Bella
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy
| | - Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy
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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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8
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Koshy AN, Ko J, Farouque O, Cooray SD, Han HC, Cailes B, Gow PJ, Weinberg L, Testro A, Lim HS, Teh AW. Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index. Am J Transplant 2021; 21:593-603. [PMID: 32530547 DOI: 10.1111/ajt.16145] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 06/01/2020] [Accepted: 06/06/2020] [Indexed: 01/25/2023]
Abstract
Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.
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Affiliation(s)
- Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Jefferson Ko
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Shamil D Cooray
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Hui-Chen Han
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Benjamin Cailes
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
| | - Paul J Gow
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Laurence Weinberg
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia.,Department of Anaesthesia, Austin Health, Melbourne, Victoria, Australia
| | - Adam Testro
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Han S Lim
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Andrew W Teh
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia.,Cardiology Department, Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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9
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Effect of liver transplantation on QT-interval prolongation and impact on mortality. Int J Cardiol 2020; 326:158-163. [PMID: 33186663 DOI: 10.1016/j.ijcard.2020.11.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/19/2020] [Accepted: 11/04/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND QT-interval prolongation is considered the electrophysiological hallmark of cirrhotic cardiomyopathy. However, the significance of QT-interval prolongation and how it is affected by liver transplantation (LT) remains unclear. METHODS Consecutive inpatients undergoing LT between 2010 and 2017 at a state-wide liver transplant center in Australia were included. Preoperative, early postoperative and long-term follow-up corrected QT-intervals (QTc) were manually measured by a cardiologist. QTc was calculated using the Bazett formula and QTc ≥440 milliseconds (ms) was considered prolonged. RESULTS Overall, 1111 ECG tracings among 408 patients (mean age 57 ± 12 years) were assessed. Pre-LT, 265 patients (65.0%) had QTc ≥440 ms and 24 patients (5.9%) had QTc ≥500 ms. In the early postoperative period, there was a significant increase in QTc compared to pre-LT (471 ± 39 vs. 452 ± 31 ms, p < 0.001) and 80 patients (20.3%) had QTc ≥500 ms. At a median of six months post-LT, there was significant reduction in mean QTc compared to pre-LT (430 ± 32 vs. 452 ± 31 ms; p < 0.001) with the QTc shortening in 73% of patients. QT-interval prolongation was not associated with postoperative complications or mortality at any time-point. CONCLUSION QT-interval prolongation is common in patients with liver cirrhosis and this metric normalized in the majority within six months post-LT. A significant increase in QTc was noted early post-LT, with over 20% demonstrating QTc ≥500 ms. QT-interval prolongation was not associated with post-transplant complications or mortality. Resolution of QT-interval prolongation suggests that this feature of cirrhotic cardiomyopathy may reverse post-transplantation.
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10
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Héla E, Sofien K, Kamel L, Asma O, Dalila G, Sondos K, Jamel K. QT interval abnormalities and heart rate variability in patients with cirrhosis. Arab J Gastroenterol 2020; 21:246-252. [PMID: 33012676 DOI: 10.1016/j.ajg.2020.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/10/2020] [Accepted: 08/11/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND AND STUDY AIMS We aimed to assess the relationship of the QT interval and heart rate variability with the severity and aetiology of cirrhosis and determine the effect of propranolol on them. PATIENTS AND METHODS This prospective study included 44 patients with cirrhosis categorised into three groups based on the Child-Pugh score: groups 1, 2 and 3 (with 12, 15 and 15 patients, respectively). Demographic characteristics, propranolol administration, severity of cirrhosis evaluated by the Child-Pugh score, aetiology of cirrhosis, and serum sodium, potassium and calcium levels were evaluated. All patients underwent 24 h-Holter monitoring. Corrected QT interval (QTc), average heart rate, standard deviation of normal-to-normal intervals (SDNN) and corrected SDNN (cSDNN) were evaluated. RESULTS The average QTc was significantly longer in group 3 than in groups 1 and 2 (453.4 ± 17.4 vs 422.8 ± 18.6 and 428.9 ± 17.24 ms, p < 0.001). The median SDNN was 70 ms and was significantly lower in group 3 vs groups 1 and 2 (77; interquartile range [IQR], 67-89.5 vs 57; IQR, 38-68 and 75 ms; IQR, 61-81 ms, p = 0.003). cSDNN was significantly lower in group 3 vs groups 1 and 2 (200.0 ± 42.6 vs 254.5 ± 75.3 and 277.8 ± 110.6 ms, p = 0.022). Propranolol administration resulted in a significant increase in the average SDNN value but had no effect on cSDNN or QTc. QTc was associated with the Child-Pugh class (p < 0.001), viral aetiology (p = 0.009) and sex (p = 0.010); SDNN was associated with the mean heart rate (p = 0.015) and Child-Pugh class (p = 0.024). CONCLUSION QTc interval prolongation and decreased SDNN are common in cirrhosis. Their prevalence is closely associated with disease severity. Propranolol has no effects on cSDNN or QTc.
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Affiliation(s)
- Elloumi Héla
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Kamoun Sofien
- Department of Cardiology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia.
| | - Ltaief Kamel
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Ouakaa Asma
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Gargouri Dalila
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Kraiem Sondos
- Department of Cardiology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Kharrat Jamel
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
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11
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Ruth ND, Drury NE, Bennett J, Kelly DA. Cardiac and Liver Disease in Children: Implications for Management Before and After Liver Transplantation. Liver Transpl 2020; 26:437-449. [PMID: 31872564 DOI: 10.1002/lt.25666] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 10/16/2019] [Indexed: 02/06/2023]
Abstract
There is close interaction between the functions of the liver and heart affecting the presentation, diagnosis, and outcome of acute and chronic cardiac and liver disease. Conditions affecting both organ systems should be considered when proposing transplantation because the interaction between cardiac disease and liver disease has implications for diagnosis, management, selection for transplantation, and, ultimately, for longterm outcomes after liver transplantation (LT). The combination of cardiac and liver disease is well recognized in adults but is less appreciated in pediatric patients. The focus of this review is to describe conditions affecting both the liver and heart and how they affect selection and management of LT in the pediatric population.
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Affiliation(s)
- Nicola D Ruth
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, United Kingdom.,Institute of Infection and Immunity, University of Birmingham, Birmingham, United Kingdom
| | - Nigel E Drury
- Department of Paediatric Cardiac Surgery, Birmingham Women's & Children's Hospital, Birmingham, United Kingdom.,Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - James Bennett
- Department of Anaesthesia, Birmingham Women's & Children's Hospital, Birmingham, United Kingdom.,Department of Anaesthesia, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Deirdre A Kelly
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, United Kingdom.,Institute of Infection and Immunity, University of Birmingham, Birmingham, United Kingdom
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12
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Raszeja-Wyszomirska J, Glowczynska R, Kostrzewa K, Janik M, Zygmunt M, Zborowska H, Krawczyk M, Niewinski G, Galas M, Krawczyk M, Zieniewicz K, Milkiewicz P, Opolski G. Evaluation of Liver Graft Recipient Workup in Predicting of Early Cardiovascular Events During Liver Transplantation: A Single-Center Experience. Transplant Proc 2018; 50:1997-2001. [PMID: 30177096 DOI: 10.1016/j.transproceed.2018.02.161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 02/06/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cardiovascular events (CVE) contribute to serious complications and death after liver transplantation (LT). Troponin I (TnI) level >0.07 mg/L and prior cardiac disease are known to be the independent predictors for posttransplant CVE. We evaluated single-center cardiac workup to predict early cardiovascular morbidity and mortality after LT. PATIENTS AND METHODS We recruited 105 consecutive liver transplant recipients (male/female, 59/46; mean age, 51.66 ± 11.67 years). The cardiological assessment at evaluation for LT included medical history, electrocardiogram, echocardiography, Holter monitoring, and exercise test. We collected data regarding CVE including hypotonia with catecholamine usage, arrhythmia, sudden cardiac death, pulmonary edema, and myocardial infarction within 7 days after LT. RESULTS CVE during LT occurred in 42 recipients (40%) and after LT in 9 patients (8.57%). Proposed cutoff level of TnI >0.07 mg/L did not correlate with CVE during operation (P = .73) or after LT (P = .47). CVE during LT was associated with arterial hypertension in medical history (P <.001), right ventricular systolic pressure (P< .05), and clinical scores: Child-Pugh (P = .04), Model for End-Stage Liver Disease (MELD) (P = .04), MELD incorporating serum sodium (P<.03), and integrated MELD score (P = .01). CVE after LT correlated only with arrhythmia (P<.001) and catecholamine usage (P < .05) perioperatively. Of interest, catecholamine usage during LT was associated with prolonged stay at the intensive care unit (P < .05). CONCLUSION The single-center algorithm with noninvasive cardiac procedures without TnI assessment is optimal in evaluation before LT; however, medical history and severity of the liver disease are crucial for short-term cardiovascular morbidity after LT.
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Affiliation(s)
- J Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - R Glowczynska
- 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
| | | | - M Janik
- Liver and Internal Medicine Unit, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Zygmunt
- Liver and Internal Medicine Unit, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - H Zborowska
- Central Laboratory, Public Central Teaching Clinical Hospital, Warsaw, Poland
| | - M Krawczyk
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany; Laboratory of Metabolic Liver Diseases, Center for Preclinical Research, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - G Niewinski
- II Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | - M Galas
- 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - M Krawczyk
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - K Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - P Milkiewicz
- Liver and Internal Medicine Unit, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - G Opolski
- 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
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13
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Q-T Interval Prolongation in Patients with Liver Cirrhosis. CURRENT HEALTH SCIENCES JOURNAL 2018; 44:274-279. [PMID: 30647948 PMCID: PMC6311219 DOI: 10.12865/chsj.44.03.11] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 09/13/2018] [Indexed: 02/07/2023]
Abstract
Liver cirrhosis (LC) is the end stage of chronic liver disease characterized by the appearance of extensive fibrosis and regeneration nodes associated with hepatocyte necrosis in liver but also by the reshuffling of hepatic architecture. The triad consisting of hepatic parenchymal necrosis, regeneration and scarring is always present regardless of the type of clinical manifestation. The Child-Pugh-Turcotte classification dates back more than 30 years and has been widely used in diagnosing and assessing the severity of liver cirrhosis. This is preferred due to a low degree of complexity and a good predictive value. Prolongation of the QT interval on the electrocardiogram is common, with a prevalence exceeding 60% in patients with advanced stage of cirrhosis. In these cases, beta blockers and antiarrhythmics should be avoided or used with caution and with close QT interval monitoring. Changes in heart rate and Q-T interval are new entities in cirrhosis complications. A prolonged Q-T interval in chronic liver disease could lead to ventricular arrhythmias and sudden death. There is no report on heart rate and Q-T interval disorders in our area.
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14
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Tsiompanidis E, Siakavellas SI, Tentolouris A, Eleftheriadou I, Chorepsima S, Manolakis A, Oikonomou K, Tentolouris N. Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity. World J Gastrointest Pathophysiol 2018; 9:28-36. [PMID: 29487764 PMCID: PMC5823700 DOI: 10.4291/wjgp.v9.i1.28] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 10/04/2017] [Accepted: 10/30/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy (CAN). METHODS A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval (QTc) and their dispersions (dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal. RESULTS QT, QTc and their dispersions were significantly longer (P < 0.01) in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient (beta) = 0.45, P = 0.02] and treatment with diuretics (beta = 0.55, P = 0.03), but not with the Child-Pugh score (P = 0.54). Prevalence of CAN was common (54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score (r = 0.33, P = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis (P = 0.03). No significant association was found between severity of CAN and QT interval duration. CONCLUSION Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease.
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Affiliation(s)
- Elias Tsiompanidis
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Spyros I Siakavellas
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Anastasios Tentolouris
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Ioanna Eleftheriadou
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Stamatia Chorepsima
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Anastasios Manolakis
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Konstantinos Oikonomou
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Nikolaos Tentolouris
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
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15
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Busk TM, Bendtsen F, Poulsen JH, Clemmesen JO, Larsen FS, Goetze JP, Iversen JS, Jensen MT, Møgelvang R, Pedersen EB, Bech JN, Møller S. Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics and renal and cardiac function in patients with cirrhosis. Am J Physiol Gastrointest Liver Physiol 2018; 314:G275-G286. [PMID: 29074483 DOI: 10.1152/ajpgi.00094.2017] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.
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Affiliation(s)
- Troels M Busk
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
| | - Jørgen H Poulsen
- Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Copenhagen , Denmark
| | - Jens O Clemmesen
- Department of Hepatology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Fin S Larsen
- Department of Hepatology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Jens P Goetze
- Department of Clinical Biochemistry, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Jens S Iversen
- Department of Nephrology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Magnus T Jensen
- Department of Cardiology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Rasmus Møgelvang
- Department of Cardiology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Erling B Pedersen
- University Clinic of Nephrology and Hypertension, Department of Medical Research and Medicine, Holstebro Hospital and Aarhus University , Aarhus , Denmark
| | - Jesper N Bech
- University Clinic of Nephrology and Hypertension, Department of Medical Research and Medicine, Holstebro Hospital and Aarhus University , Aarhus , Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
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16
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Vasavan T, Ferraro E, Ibrahim E, Dixon P, Gorelik J, Williamson C. Heart and bile acids - Clinical consequences of altered bile acid metabolism. Biochim Biophys Acta Mol Basis Dis 2018; 1864:1345-1355. [PMID: 29317337 DOI: 10.1016/j.bbadis.2017.12.039] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 12/18/2017] [Accepted: 12/22/2017] [Indexed: 12/11/2022]
Abstract
Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids.
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Affiliation(s)
- Tharni Vasavan
- Department of Women and Children's Health, King's College London, Guy's Campus, Hodgkin Building, SE1 1UL London, United Kingdom
| | - Elisa Ferraro
- National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, Du Cane Road, W12 0NN London, United Kingdom
| | - Effendi Ibrahim
- National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, Du Cane Road, W12 0NN London, United Kingdom; Faculty of Medicine, MARA University of Technology, 40000 Sungai Buloh, Malaysia
| | - Peter Dixon
- Department of Women and Children's Health, King's College London, Guy's Campus, Hodgkin Building, SE1 1UL London, United Kingdom
| | - Julia Gorelik
- National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, Du Cane Road, W12 0NN London, United Kingdom
| | - Catherine Williamson
- Department of Women and Children's Health, King's College London, Guy's Campus, Hodgkin Building, SE1 1UL London, United Kingdom.
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17
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Symptomatic Heart Failure After Transjugular Intrahepatic Portosystemic Shunt Placement: Incidence, Outcomes, and Predictors. Cardiovasc Intervent Radiol 2017; 41:564-571. [PMID: 29181605 DOI: 10.1007/s00270-017-1848-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 11/14/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE To assess the incidence of symptomatic heart failure (SHF) occurring after transjugular intrahepatic portosystemic shunt (TIPS) placement, identify potential predictors of SHF, and evaluate clinical presentation and outcomes in cases of post-TIPS SHF. MATERIALS AND METHODS A prospectively maintained TIPS database was used to identify patients who underwent new TIPS placements at a large urban tertiary care center between 1995 and 2014. SHF was defined as otherwise unexplained new-onset dyspnea, hypoxemia, radiologic pulmonary edema, an increased need for diuretics, or need for intubation within 7 days after TIPS placement. Cases of deaths occurring within 7 days due to septic shock, continuing gastrointestinal bleed, or multi-organ failure were excluded. A control group consisting of a random sample of 40 patients from the same TIPS database was created. Uni-variable analysis was performed to assess differences between patients with and without post-TIPS SHF. RESULTS Of the 934 TIPS procedures performed during the study period, 883 met the inclusion criteria. Eight (0.9%) patients developed SHF, usually manifested by hypoxemia (50%) or dyspnea (25%) within 48 h. Patients with SHF had higher pre-TIPS right atrial (p = 0.03) and portal vein (p = 0.01) pressures, higher albumin (p = 0.02), and higher prothrombin time (p = 0.02). CONCLUSION Post-TIPS SHF is rare. Higher pre-TIPS right atrial and portal vein pressures are likely to predispose patients to this complication. Close monitoring may be warranted in these patients. In our eight patients, post-TIPS SHF did not result in poor outcomes.
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18
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Kim SM, George B, Alcivar-Franco D, Campbell CL, Charnigo R, Delisle B, Hundley J, Darrat Y, Morales G, Elayi SC, Bailey AL. QT prolongation is associated with increased mortality in end stage liver disease. World J Cardiol 2017; 9:347-354. [PMID: 28515853 PMCID: PMC5411969 DOI: 10.4330/wjc.v9.i4.347] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Revised: 01/13/2017] [Accepted: 02/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality.
METHODS The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease.
RESULTS Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation.
CONCLUSION QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.
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19
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Milić S, Lulić D, Štimac D, Ružić A, Zaputović L. Cardiac manifestations in alcoholic liver disease. Postgrad Med J 2016; 92:235-9. [PMID: 26850503 DOI: 10.1136/postgradmedj-2015-133755] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 01/04/2016] [Indexed: 12/11/2022]
Abstract
Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.
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Affiliation(s)
- Sandra Milić
- Department of Gastroenterology, Internal Medicine Clinic, University Hospital Rijeka, Rijeka, Croatia
| | - Davorka Lulić
- Department of Cardiovascular Disease, Internal Medicine Clinic, University Hospital Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Internal Medicine Clinic, University Hospital Rijeka, Rijeka, Croatia
| | - Alen Ružić
- Department of Cardiovascular Disease, Internal Medicine Clinic, University Hospital Rijeka, Rijeka, Croatia
| | - Luka Zaputović
- Department of Cardiovascular Disease, Internal Medicine Clinic, University Hospital Rijeka, Rijeka, Croatia
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20
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Wiese S, Hove JD, Møller S. Cardiac imaging in patients with chronic liver disease. Clin Physiol Funct Imaging 2015; 37:347-356. [PMID: 26541640 DOI: 10.1111/cpf.12311] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 09/18/2015] [Indexed: 12/15/2022]
Abstract
Cirrhotic cardiomyopathy (CCM) is characterized by an impaired contractile response to stress, diastolic dysfunction and the presence of electrophysiological abnormalities, and it may be diagnosed at rest in some patients or demasked by physiological or pharmacological stress. CCM seems to be involved in the development of hepatic nephropathy and is associated with an impaired survival. In the field of cardiac imaging, CCM is not yet a well-characterized entity, hence various modalities of cardiac imaging have been applied. Stress testing with either physiologically or pharmacologically induced circulatory stress has been used to assess systolic dysfunction. Whereas echocardiography with tissue Doppler is by far the most preferred method to detect diastolic dysfunction with measurement of E/A- and E/E'-ratio. In addition, echocardiography may also possess the potential to evaluate systolic dysfunction at rest by application of new myocardial strain techniques. Experience with other modalities such as cardiac magnetic resonance imaging and cardiac computed tomography is limited. Future studies exploring these imaging modalities are necessary to characterize and monitor the cardiac changes in cirrhotic patients.
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Affiliation(s)
- Signe Wiese
- Centre of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 239, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.,Gastro Unit, Medical Division, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens D Hove
- Department of Cardiology, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 239, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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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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22
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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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23
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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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Tuttolomondo A, Buttà C, Casuccio A, Di Raimondo D, Serio A, D'Aguanno G, Pecoraro R, Renda C, Giarrusso L, Miceli G, Cirrincione A, Pinto A. QT Indexes in Cirrhotic Patients: Relationship with Clinical Variables and Potential Diagnostic Predictive Value. Arch Med Res 2015; 46:207-213. [PMID: 25843561 DOI: 10.1016/j.arcmed.2015.03.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 03/25/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS A wide spectrum of cardiovascular changes characterizes cirrhosis, ranging from subclinical alterations to hyperkinetic syndrome. We looked for ECG markers of ventricular repolarization in a population of patients with cirrhosis in comparison to patients without cirrhosis and we investigated the relationship between these and other clinical and laboratory variables. METHODS In 149 patients with cirrhosis and 152 controls, we measured QT maximum interval (QTmax), QT corrected interval (QTc), QT minimum interval (QTmin), QT dispersion (QTdisp), QT peak and T peak-to-end (TpTe). RESULTS In subjects with cirrhosis, in comparison with controls, we observed a higher mean QTmax, mean QTc, mean QTmin, mean QTdisp and mean TpTe. At Cox regression analysis, diastolic blood pressure and beta-blocker treatment were significantly associated with mean QTmax, hypertension with mean QTmin and mean QTc, diastolic blood pressure, beta-blockers and ACE-inhibitors/ARBs with QT disp, and beta-blockers with TpTe. Analysis of ROC curves showed a significant area under curve towards cirrhosis diagnosis, respectively, for a cut-off value of > 400 msec of QTmax, > 360 msec of QTmin, > 450 msec of QTc, > 105 msec of TpTe and > 55 msec of QTdisp. CONCLUSIONS Our study shows that QT indexes are altered in cirrhotic patients and have a potential diagnostic predictive value.
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Affiliation(s)
- Antonino Tuttolomondo
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Carmelo Buttà
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy.
| | - Alessandra Casuccio
- Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Domenico Di Raimondo
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Antonia Serio
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Gisella D'Aguanno
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Rosaria Pecoraro
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Chiara Renda
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Lucia Giarrusso
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Giuseppe Miceli
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Anna Cirrincione
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
| | - Antonio Pinto
- Internal Medicine and Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy
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Investigation of cardiomyopathy in children with cirrhotic and noncirrhotic portal hypertension. J Pediatr Gastroenterol Nutr 2015; 60:177-81. [PMID: 25250684 DOI: 10.1097/mpg.0000000000000580] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Cirrhotic cardiomyopathy (CCMP) is a functional disorder characterized by electrophysiological disturbances, and diastolic and/or systolic dysfunction in patients with liver disease. This disorder is a well-defined entity in adults, but pediatric data are limited. The aim of the study was to determine the incidence, features, and risk factors of CCMP in children with portal hypertension (PHT). METHODS This study included 50 children with cirrhotic PHT (40/50) and noncirrhotic PHT (10/50). Fifty healthy children were also selected for the control group. Electrocardiography and echocardiography were used to evaluate cardiac functions. Corrected QT (QTc) ≥ 0.45 was accepted as prolonged on electrocardiography. The study group was divided into 3 groups: cirrhotic, noncirrhotic, and control. Then, the CCMP group was created according to the diagnostic criteria. Latent CCMP was diagnosed in the presence of prolonged-QTc along with a minor criterion (tachycardia). Manifest CCMP was diagnosed in the presence of at least 2 major criteria (prolonged-QTc along with abnormal echocardiographic findings). Moreover, in this study, the risk factors for CCMP were investigated. RESULTS The CCMP group included 10 cases (20%). Nine of these cases had latent CCMP (18%), and the remaining one (2%) had manifest CCMP. All of the cases with CCMP had cirrhosis and ascites. None of the patients with CCMP had severe cardiac symptoms, but they were already using some cardioprotective drugs such as propanolol and spironolactone. As risk factors for CCMP, pediatric end-stage liver disease scores, Child-Pugh scores, and ascites grades were found to be significant for the determination of CCMP. The most important risk factor was ascites severity (P = 0.001, odds ratio 9.4). CONCLUSIONS Approximately 20% of children with PHT have CCMP. A detailed cardiac examination should be carried out periodically in children with cirrhotic PHT, especially in the presence of ascites and high Child-Pugh score.
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Wu SJ, Yan HD, Zheng ZX, Shi KQ, Wu FL, Xie YY, Fan YC, Ye BZ, Huang WJ, Chen YP, Zheng MH. Establishment and validation of ALPH-Q score to predict mortality risk in patients with acute-on-chronic hepatitis B liver failure: a prospective cohort study. Medicine (Baltimore) 2015; 94:e403. [PMID: 25590846 PMCID: PMC4602548 DOI: 10.1097/md.0000000000000403] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 11/12/2014] [Accepted: 12/07/2014] [Indexed: 12/12/2022] Open
Abstract
Currently, there are no robust models for predicting the outcome of acute-on-chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a new prognostic scoring system, named ALPH-Q, that integrates electrocardiography parameters that may be used to predict short-term mortality of patients with ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q score was constructed by Cox proportional hazard regression analysis and was validated in an independent patient cohort. The area under the receiver-operating characteristic curve was used to compare the performance of different models, including APLH-Q, Child-Pugh score (CPS), model of end-stage liver disease (MELD), and a previously reported logistic regression model (LRM). The APLH-Q score was constructed with 5 independent risk factors, including age (HR = 1.034, 95% CI: 1.007-1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366-5.548), prothrombin time (HR = 1.031, 95% CI: 1.002-1.062), hepatic encephalopathy (HR = 2.703, 95% CI: 1.630-4.480), and QTc (HR = 1.008, 95% CI: 1.001-1.016). The performance of the ALPH-Q score was significantly better than that of MELD and CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P < 0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs 0.825, 0.837 vs 0.818, respectively).We have developed a novel APLH-Q score with greater performance than CPS, MELD, and LRM for predicting short-term mortality of patients with ACHBLF.
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Affiliation(s)
- Sheng-Jie Wu
- From the Department of Cardiovascular Medicine (S-JW, Z-XZ, B-ZY, W-JH), the Heart Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou; Department of Infectious Diseases (H-DY), Ningbo No. 2 Hospital, Ningbo; Department of Infection and Liver Diseases (K-QS, F-LW, Y-PC, M-HZ), Liver Research Center (K-QS, F-LW, Y-PC, M-HZ), the First Affiliated Hospital of Wenzhou Medical University; Institute of Hepatology, Wenzhou Medical University; Department of Clinical Laboratory (Y-YX), the First Affiliated Hospital of Wenzhou Medical University, Wenzhou; Department of Hepatology (Y-CF), Qilu Hospital of Shandong University, Jinan, China
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Kim MS, Kim NY, Park JE, Nam SH. Ventricular arrhythmia in patients with prolonged QT interval during liver transplantation: two cases report. Korean J Anesthesiol 2014; 67:416-20. [PMID: 25558343 PMCID: PMC4280480 DOI: 10.4097/kjae.2014.67.6.416] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 01/28/2014] [Accepted: 02/04/2014] [Indexed: 11/10/2022] Open
Abstract
QT interval prolongation is associated with an increased risk of ventricular arrhythmia in various conditions. Cardiac electrophysiologic abnormalities including QT interval prolongation are well documented in patients with advanced liver cirrhosis. We report two cases of patients with QT interval prolongation on preoperative electrocardiography who exhibited repetitive ventricular arrhythmias with significant hemodynamic deterioration during liver transplantation. For the treatment and prevention of ventricular arrhythmias during the intraoperative period, we performed intravenous administration of lidocaine and isoproterenol, corrected imbalances of electrolytes including potassium and magnesium, and prepared a defibrillator. These cases emphasize that preoperative recognition of QT interval prolongation and adequate management to prevent fatal arrhythmias are important in patients undergoing liver transplantation.
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Affiliation(s)
- Min-Soo Kim
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea. ; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Na Young Kim
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea. ; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Eun Park
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Soon Ho Nam
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea. ; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
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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: 172] [Impact Index Per Article: 15.6] [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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Pellicori P, Torromeo C, Calicchia A, Ruffa A, Di Iorio M, Cleland JGF, Merli M. Does cirrhotic cardiomyopathy exist? 50 years of uncertainty. Clin Res Cardiol 2013; 102:859-64. [PMID: 23995321 DOI: 10.1007/s00392-013-0610-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2013] [Accepted: 08/14/2013] [Indexed: 02/08/2023]
Abstract
Subtle abnormalities of cardiac structure or function are often identified in patients with liver cirrhosis and have been termed cirrhotic cardiomyopathy. However, in the absence of a precise definition, its diagnosis remains a challenge. Cardiac dysfunction in patients with cirrhosis can often be attributed to concomitant diseases such as hypertension, ischaemic heart disease or excess alcohol consumption in many patients. Further research is required to identify the existence, origin and importance of abnormal cardiac function due specifically to liver disease. Cardiac dysfunction may be masked by treatments given to cirrhotic patients, such as mineral-corticoid receptor antagonists, or by co-existing conditions, such as anaemia. New imaging tests or plasma biomarkers might be able to detect abnormal cardiac function at an early stage of its development.
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Affiliation(s)
- Pierpaolo Pellicori
- Department of Academic Cardiology, Hull and East Yorkshire Medical Research and Teaching Centre MRTDS (Daisy) Building, Entrance 2 Castle Hill Hospital, Cottingham, Kingston upon Hull, HU16 5JQ, UK,
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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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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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Abstract
There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic cardiomyopathy. Electrophysiological abnormalities include prolonged QT interval, chronotropic incompetance, and electromechanical uncoupling. No specific therapy can be recommended, but it should be supportive and directed against the heart failure. Numerous conditions affect both the heart and the liver such as infections, inflammatory and systemic diseases, and chronic alcoholism. The risk and prevalence of coronary artery disease are increasing in cirrhotic patients and since the perioperative mortality is high, a careful cardiac evaluation of such patients is required prior to orthotopic liver transplantation.
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Affiliation(s)
- Søren Møller
- Centre of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, The Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Qureshi W, Mittal C, Ahmad U, Alirhayim Z, Hassan S, Qureshi S, Khalid F. Clinical predictors of post-liver transplant new-onset heart failure. Liver Transpl 2013; 19:701-10. [PMID: 23554120 DOI: 10.1002/lt.23654] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2012] [Accepted: 03/27/2013] [Indexed: 12/12/2022]
Abstract
Objectives of this study were (1) to evaluate preoperative predictors of systolic and diastolic heart failure in patients undergoing liver transplantation (LT) and (2) to describe the prognostic implications of systolic and diastolic heart failure in these patients. The onset of heart failure after orthotopic LT remains poorly understood. Data were obtained for all LT recipients between January 2000 and December 2010. The primary outcome was post-LT heart failure: systolic (ejection fraction ≤ 50%), diastolic, or mixed heart failure. Patients underwent echocardiographic evaluation before and after LT. Pretransplant variables were evaluated as predictors of heart failure with Cox proportional hazards model. 970 LT recipients were followed for 5.3 ± 3.4 years. Ninety-eight patients (10.1%) developed heart failure in the posttransplant period. There were 67 systolic (6.9%), 24 diastolic (2.5%), and 7 mixed systolic/diastolic (0.7%) heart failures. Etiology was ischemic in 18 (18.4%), tachycardia-induced in 8 (8.2%), valvular in 7 (7.1%), alcohol-related in 4 (4.1%), hypertensive heart disease in 3 (3.1%), and nonischemic in majority of patients (59.2%). Pretransplant grade 3 diastolic dysfunction, diabetes, hypertension, mean arterial pressure ≤ 65 mm Hg, mean pulmonary artery pressure ≥ 30 mm Hg, mean pulmonary capillary wedge pressure ≥ 15 mm Hg, hemodialysis, brain natriuretic peptide level and QT interval > 450 ms were found to be predictive for the development of new-onset systolic heart failure. However beta-blocker use before LT and tacrolimus after LT were associated with reduced development of new-onset systolic heart failure. In conclusion, pretransplant risk factors, hemodynamic variables, and echocardiographic variables are important predictors of post-LT heart failure. In patients undergoing LT, postoperative onset of systolic or diastolic heart failure was found to be an independent predictor of mortality.
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Affiliation(s)
- Waqas Qureshi
- Department of Internal Medicine, Henry Ford Hospital/Wayne State University School of Medicine, Detroit, MI 48202, USA.
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Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther 2013; 37:1132-56. [PMID: 23638982 DOI: 10.1111/apt.12324] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Revised: 11/30/2012] [Accepted: 04/08/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes. AIM To provide a practical approach to prescribing medications for cirrhotic patients. METHODS An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed. RESULTS Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2-3 g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care. CONCLUSIONS Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.
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Affiliation(s)
- J H Lewis
- Division of Gastroenterology and Hepatology, Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
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Bernardi M, Maggioli C, Dibra V, Zaccherini G. QT interval prolongation in liver cirrhosis: innocent bystander or serious threat? Expert Rev Gastroenterol Hepatol 2012; 6:57-66. [PMID: 22149582 DOI: 10.1586/egh.11.86] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The ECG QT interval measures the length of ventricular systole. Its prolongation is essentially caused by a delayed repolarization phase, and is associated with an increased risk of ventricular arrhythmias and sudden death in several congenital and acquired conditions. Abnormalities in cardiac electrophysiology are well documented in patients with liver cirrhosis, and the prolonged QT interval has emerged as the electrophysiological hallmark of cirrhotic cardiomyopathy. This article will focus on: first, the epidemiology of QT interval prolongation in cirrhosis; second, the potential molecular mechanisms responsible for the pathogenesis of this electrophysiological abnormality and the putative role of circulating cardiotoxins; third, its prognostic meaning; and fourth, its clinical relevance, in terms of the association between the presence of a long QT interval and the occurrence of ventricular arrhythmias in cirrhotic patients treated with drugs known to increase the QT length or exposed to stressful conditions, such as liver transplantation, gastrointestinal bleeding and shock.
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Affiliation(s)
- Mauro Bernardi
- Unità Operativa Semeiotica Medica, Department of Clinical Medicine, Alma Mater Studiorum University of Bologna, Via Albertoni 15, Bologna 40138, Italy.
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Abstract
Cardiac dysfunction in patients with cirrhosis and potential clinical implications have long been known, but the pathophysiology and potential targets for therapeutic intervention are still under investigation and are only now becoming understood. The pathophysiological changes result in systolic dysfunction, diastolic dysfunction, and electrophysiological changes. Here, we aim to review cirrhotic cardiomyopathy from a cellular and physiological model and how these patients develop overt heart failure in the setting of stress, such as infection, ascites, and procedures including transjugular intrahepatic portosystemic shunt, portocaval shunts, and orthotopic liver transplantation. We will also review the most current, although limited, available therapeutic modalities.
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Drug-induced QT prolongation in cirrhotic patients with transjugular intrahepatic portosystemic shunt. J Clin Gastroenterol 2011; 45:638-42. [PMID: 20962670 DOI: 10.1097/mcg.0b013e3181f8c522] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
GOALS AND BACKGROUND Nearly 40% of cytochrome P450 3A (CYP3A) activity is located in the small intestine. An earlier study has shown that cirrhotics with transjugular intrahepatic portosystemic shunts (TIPS) have diminished intestinal CYP3A activity. We hypothesized that oral CYP3A substrates known to prolong QT interval may cause further prolongation of the QT interval in cirrhotic patients with TIPS. STUDY A total of 23 patients (9 healthy controls, 6 cirrhotics without and 8 cirrhotics with TIPS) participated in a study that tested this hypothesis using erythromycin as the probe drug. Participants with cirrhosis with and without TIPS were matched for age, sex, race, BMI and etiology of liver disease. Serial electrocardiograms were obtained at baseline, after single dose of erythromycin 500 milligrams, and after 7 days of erythromycin (500 milligrams orally twice daily). QT intervals were measured in 3 consecutive beats in 3 leads and corrected QT intervals (QTc) were obtained using various correction formulae. The maximal QTc change (ΔQTc Max) after single and multiple dose administration was the primary outcome. RESULTS At baseline, the QTc intervals (mean±S.E) in cirrhotics with TIPS (418±6 msec) and cirrhosis (431±6 msec) were significantly higher compared with controls (388±9 msec, P=0.021). After a single dose of erythromycin, there was no significant difference among the 3 groups in ΔQTc Max (P=0.7). However, after a 7 day course, cirrhotics with TIPS developed significantly greater ΔQTc Max (179.5±67.8 msec) compared with cirrhotics (31.2±9.5 msec) and healthy controls (38.3±3.3 msec) (P=0.03). CONCLUSION This study suggests that patients with TIPS are potentially at increased risk for abnormal QT prolongation when exposed to oral CYP 3A substrates with QT prolonging effect.
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Ripoll C, Yotti R, Bermejo J, Bañares R. The heart in liver transplantation. J Hepatol 2011; 54:810-22. [PMID: 21145840 DOI: 10.1016/j.jhep.2010.11.003] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2010] [Revised: 09/27/2010] [Accepted: 11/04/2010] [Indexed: 02/08/2023]
Abstract
The heart and liver are organs that are closely related in both health and disease. Patients who undergo liver transplantation may suffer from heart disease that is: (a) related to the original cause of the liver disease such as hemochromatosis, (b) related to the liver disease itself, or (c) related to other associated conditions. Furthermore, liver transplantation is one of the most cardiovascular stressful events that a patient with cirrhosis may undergo. After liver transplantation, the progression of pre-existing or the development of new-onset cardiac disease may occur. This article reviews the relationship between the heart and liver transplantation in the pre-transplant, intra-operative, and post-transplant periods.
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Affiliation(s)
- Cristina Ripoll
- Department of Digestive Disease, Ciber EHD Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
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Møller S, Henriksen JH. Cirrhotic cardiomyopathy. J Hepatol 2010; 53:179-90. [PMID: 20462649 DOI: 10.1016/j.jhep.2010.02.023] [Citation(s) in RCA: 230] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2009] [Revised: 01/26/2010] [Accepted: 02/04/2010] [Indexed: 12/13/2022]
Abstract
Increased cardiac output was first described in patients with cirrhosis more than fifty years ago. Later, various observations have indicated the presence of a latent cardiac dysfunction, which includes a combination of reduced cardiac contractility with systolic and diastolic dysfunction and electrophysiological abnormalities. This syndrome is termed cirrhotic cardiomyopathy. Results of experimental studies indicate the involvement of several mechanisms in the pathophysiology, such as reduced beta-adrenergic receptor signal transduction, altered transmembrane currents and electromechanical coupling, nitric oxide overproduction, and cannabinoid receptor activation. Systolic incompetence in patients can be revealed by pharmacological or physical strain and during stressful procedures, such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. Systolic dysfunction has recently been implicated in development of renal failure in advanced disease. Diastolic dysfunction reflects delayed left ventricular filling and is partly attributed to ventricular hypertrophy, subendocardial oedema, and altered collagen structure. The QT interval is prolonged in about half of the cirrhotic patients and it may be normalised by beta-blockers. No specific therapy for cirrhotic cardiomyopathy can be recommended, but treatment should be supportive and directed against the cardiac dysfunction. Future research should better describe the prevalence, impact on morbidity and survival, and look for potential treatments.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.
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Shafaroodi H, Ebrahimi F, Moezi L, Hashemi M, Doostar Y, Ghasemi M, Dehpour AR. Cholestasis induces apoptosis in mice cardiac cells: the possible role of nitric oxide and oxidative stress. Liver Int 2010; 30:898-905. [PMID: 20492516 DOI: 10.1111/j.1478-3231.2010.02249.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND/AIMS Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts. METHODS Cholestasis was induced by bile duct-ligation, and sham-operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment with l-NAME, a non-selective inhibitor of NO synthase, or with d-NAME, an inactive isomer of l-NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined. RESULTS Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment with l-NAME, but not d-NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified by d-NAME treatment. By l-NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased by l-NAME treatment. CONCLUSION In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice.
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Affiliation(s)
- Hamed Shafaroodi
- Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
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Pulmonary oedema after therapeutic ascitic paracentesis: a case report and literature review of the cardiac complications of cirrhosis. Eur J Gastroenterol Hepatol 2010; 22:241-5. [PMID: 19801941 DOI: 10.1097/meg.0b013e32833110f7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
In this study, we describe the development of acute pulmonary oedema and cardiac arrest after therapeutic ascitic paracentesis, in a gentleman with decompensated liver cirrhosis. There was no previous history of cardiorespiratory symptoms or disease. Postmortem examination revealed oedematous and congested lungs with bilateral pleural effusions; in addition, the right heart was dilated and congested. Micronodular cirrhosis was present with histological features of alpha1 antitrypsin deficiency. This is the first study of acute cardiac decompensation after large volume paracentesis. Owing to the postmortem findings, underlying asymptomatic cardiorespiratory disease may have been present. Cirrhosis is associated with cardiovascular complications including cirrhotic cardiomyopathy, portopulmonary hypertension and hepatopulmonary syndrome which may manifest or worsen under situations of haemodynamic stress. This report thus raises the question whether routine screening for cardiovascular abnormalities is warranted in patients with decompensated cirrhosis, particularly before the procedures such as paracentesis that impose significant haemodynamic strain.
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Abstract
AIM OF THE STUDY To study the cardiac function in patients with liver cirrhosis. METHODS Thirty patients with liver cirrhosis, referred to as group I (G 1), were selected. They were subdivided according to Child-Pugh classification into 3 groups: A, B, and C. Thirty healthy subjects, referred to as group II (G II), were selected as a control group. All persons were examined by resting ECG, abdominal ultrasound, laboratory tests, and echo-Doppler evaluation of systolic and diastolic functions of both ventricles using 2-D, M-mode, conventional Doppler, and tissue Doppler parameters. RESULTS Systolic and diastolic blood pressures were significantly reduced with increased resting HR and CO in G I (p<0.05). The QTc interval was prolonged in G I (0.45±0.03 ms; p<0.001) but EDV, ESV, EF%, and S´ velocity were not significantly different in both study groups for both ventricles. LAD, MPI, LVPWT, and, IVST were significantly increased in G I (p<0.05). E/A and E´/A´ ratios were reversed in G I with increased DT/E for both ventricles (p<0.001). No significant difference was found among Child A, B, C subgroups except for the LAD which was significantly increased in Child C (p<0.05). There was a significant inverse correlation between serum albumin and left ventricular MPI (r=-0.4, p<0.05). CONCLUSION Many cardiovascular abnormalities occur in patients with liver cirrhosis that mandate echocardiographic evaluation especially in cases who undergo any procedure which may affect the hemodynamics.
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QT interval prolongation and decreased heart rate variability in cirrhotic patients: relevance of hepatic venous pressure gradient and serum calcium. Clin Sci (Lond) 2009; 116:851-9. [PMID: 19076059 DOI: 10.1042/cs20080325] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A prolongation of QT interval has been shown in patients with cirrhosis and it is considered as part of the definition of the so-called 'cirrhotic cardiomyopathy'. The aim of the present study was to assess the determinants of QT interval prolongation in cirrhotic patients. Forty-eight male patients with different stages of liver disease were divided into three subgroups according to the Child-Pugh classification. All patients underwent a 24-h ECG Holter recording. The 24-h mean of QT intervals corrected for heart rate (termed QTc) and the slope of the regression line QT/RR were calculated. HRV (heart rate variability), plasma calcium and potassium concentration and HVPG (hepatic venous pressure gradient) were measured. QTc was progressively prolonged from Child A to Child C patients (P=0.001). A significant correlation between QTc and HVPG was found (P=0.003). Patients with alcohol-related cirrhosis presented QTc prolongation more frequently than patients with post-viral cirrhosis (P<0.001). The QT/RR slope was steeper in subjects with alcoholic aetiology as compared with viral aetiology (P=0.02), suggesting that these patients have a further QTc prolongation when heart rate decreases. The plasma calcium concentration was inversely correlated with QTc (P<0.001). The presence of severe portal hypertension was associated with decreased HRV (P<0.001). Cirrhotic patients with a more severe disease, especially of alcoholic aetiology, who have greater HVPG and lower calcium plasma levels, have an altered ventricular repolarization and a reduced vagal activity to the heart, which may predispose to life-threatening arrhythmias.
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Arikan C, Kilic M, Tumgor G, Levent E, Yuksekkaya HA, Yagci RV, Aydogdu S. Impact of liver transplantation on rate-corrected QT interval and myocardial function in children with chronic liver disease*. Pediatr Transplant 2009; 13:300-306. [PMID: 18537904 DOI: 10.1111/j.1399-3046.2008.00909.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Prolonged QTc interval (>440 ms) is a common abnormality in adult patients with CLD and has been reported to predict patient survival. In this study, 88 children who underwent evaluation for LT, including a 12-lead electrocardiogram and echocardiogram included to determine the frequency of QTc prolongation and related factors in children with CLD and the effect of LT on these factors. Sixty-nine healthy, age- and sex-matched children served as controls. QTc interval was prolonged in 40 CLD patients (45.4%). It was found to be related to PELD score and presence of portal hypertension. Mean QTc was higher in patients who died prior to LT than in the survivors without LT. Mortality risk was increased 3.66-fold in patients with prolonged QTc (p = 0.001, 95% CI: 2-7.2). Cox regression analysis showed that only PELD score was an independent predictor of survival (p = 0.001, beta = -0.41, 95% CI: 5.58-1.82). Five of 48 transplanted children died within three months post-transplant; QTc was not related to post-transplant survival (p = 0.27). QTc normalized in 63.8% patients after LT. After LT, LAD, LVEF, and LVPWT decreased. In conclusion, QTc prolongation is common in children with CLD and associated with high mortality. It may be useful for assessment of the severity of CLD and for the timing for transplantation.
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Affiliation(s)
- Cigdem Arikan
- Departments of Pediatric Gastroenterology, Hepatology and Nutrition, Ege University School of Medicine, 250. sok. No:6 D:1Bornova 35500 Izmir, Turkey.
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Abstract
Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities, termed cirrhotic cardiomyopathy. Pathophysiological mechanisms include reduced beta-adrenergic receptor signal transduction and defective cardiac electromechanical coupling. However, the QT interval is prolonged in approximately half of patients with cirrhosis and it may be improved by beta-blockers. No specific therapy can be recommended but it should be supportive and directed against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease are increasing in cirrhotic patients and since perioperative mortality is high, careful evaluation of such patients with dobutamine stress echocardiography, coronary angiography and myocardial perfusion imaging is required prior to liver transplantation. Future research should focus on beneficial effects of treatment on cardiac function and mortality.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, 239, Hvidovre Hospital, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.
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Abstract
Cirrhotic cardiomyopathy is a recently recognized condition in cirrhosis consisting of systolic incompetence under condition of stress, diastolic dysfunction related to altered diastolic relaxation, and electrophysiological abnormalities in the absence of any known cardiac disease. It can be diagnosed by using a combination of electrocardiograph, 2-dimensional echocardiography, and various serum markers such as brain natriuretic factor. The underlying pathogenetic mechanisms include abnormalities in the beta-adrenergic signaling pathway, altered cardiomyocyte membrane fluidity, increased myocardial fibrosis, cardiomyocyte hypertrophy, and ion channel defects. Various compounds for which levels are elevated in cirrhosis such as nitric oxide and carbon monoxide can also exert a negative inotropic effect on the myocardium, whereas excess sodium and volume retention can lead to myocardial hypertrophy. Various toxins can also aggravate the ion channel defects, thereby widening the QRS complex causing prolonged QT intervals. Clinically, systolic incompetence is most evident when cirrhotic patients are placed under stress, whether physical or pharmacological, or when the extent of peripheral arterial vasodilatation demands an increased cardiac output as in the case of bacterial infections. Acute volume overload such as immediately after insertion of a transjugular intrahepatic portosystemic shunt or after liver transplantation can also tip these cirrhotic patients into cardiac failure. Treatment of cirrhotic cardiomyopathy is unsatisfactory. There is some evidence that beta-blockade may help some cirrhotic patients with baseline prolonged QT interval. Long-term aldosterone antagonism may help reduce myocardial hypertrophy. Future studies should include further elucidation of pathogenetic mechanisms so as to develop effective treatment strategies.
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Affiliation(s)
- Florence Wong
- Department of Medicine, Toronto General Hospital, University of Toronto, 9th floor, North Wing, Room 983, 200 Elizabeth Street, Toronto, ON, Canada, M5G 2C4,
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The association of the metabolic syndrome with QTc interval in NHANES III. Eur J Epidemiol 2008; 23:459-65. [DOI: 10.1007/s10654-008-9252-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2007] [Accepted: 04/09/2008] [Indexed: 10/22/2022]
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Zambruni A, Trevisani F, Di Micoli A, Savelli F, Berzigotti A, Bracci E, Caraceni P, Domenicali M, Felline P, Zoli M, Bernardi M. Effect of chronic beta-blockade on QT interval in patients with liver cirrhosis. J Hepatol 2008; 48:415-21. [PMID: 18194821 DOI: 10.1016/j.jhep.2007.11.012] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2007] [Revised: 10/31/2007] [Accepted: 11/21/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS QT interval prolongation is frequent in cirrhosis, predicts a poor prognosis and may trigger severe ventricular arrhythmias. Our aim was to evaluate the effect of chronic beta-blockade on QT prolongation. METHODS Clinical and laboratory evaluation, ECG and hepatic vein pressure gradient (HVPG) measurement were performed in 30 cirrhotic patients before and 1-3 months after prophylactic nadolol. QT was corrected for heart rate by the cirrhosis-specific formula and other formulas. RESULTS QT(cirrhosis) was prolonged in 10 patients (33%); HVPG was increased in all cases. QT(cirrhosis) was correlated with the Child-Pugh score (r=0.40; p=0.027). Nadolol shortened QT interval only with the Bazett formula (p=0.01), remaining unchanged with the other formulas. The QT interval shortened only if prolonged at baseline (from 473.3+/-5.5 to 458.4+/-6.5 ms; p=0.007), while it lengthened when normal (from 429.8+/-3.1 to 439.3+/-2.9 ms; p=0.01). QTc changes were directly related to the baseline value (p<0.001). HVPG decreased from 19.4+/-0.8 to 15.6+/-1.3 mmHg (p=0.004). The HVPG changes did not correlate with QTc changes. CONCLUSIONS Chronic beta-blockade shortens the QT interval only in patients with prolonged baseline values, and this is likely due to a direct cardiac effect.
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Affiliation(s)
- Andrea Zambruni
- Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Semeiotica Medica, Alma Mater Studiorum, Università di Bologna, Bologna, Italy.
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Hansen S, Møller S, Bendtsen F, Jensen G, Henriksen JH. Diurnal variation and dispersion in QT interval in cirrhosis: relation to haemodynamic changes. J Hepatol 2007; 47:373-80. [PMID: 17459513 DOI: 10.1016/j.jhep.2007.03.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2006] [Revised: 02/15/2007] [Accepted: 03/05/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS A long QT(C) interval has been described in a substantial fraction of patients with cirrhosis, but information on QT variation and dispersion is sparse. The aim was to determine QT variation with time and QT dispersion (QT(disp)). METHODS The study population comprised 23 patients with cirrhosis, undergoing a haemodynamic investigation. 24-h 12 lead Holter monitoring provided information on QT and heart rate variability. RESULTS Mean QT(C) was above upper normal limit (440 ms(1/2)) in eleven patients (47%) and significantly higher than in controls (441 vs 400 ms(1/2), p<0.01). The minimum value of QT(C) (but not the maximum value) showed a significant diurnal variation both in cirrhosis and controls. QT(disp) in cirrhosis and controls was similar (33 vs 36 ms, ns), but related to indicators of liver dysfunction, central circulation time, and arterial blood pressure (r=0.44-0.58, p=0.03-0.001). No diurnal variation of QT(disp) was found in cirrhosis. Heart rate variability was reduced with a significant relation to central hypovolaemia (r=0.55, p=0.01). CONCLUSIONS Twenty-four hours QT(C) is prolonged in a substantial fraction of patients with cirrhosis, but with normal diurnal variation. The combination of long QT(C) and normal QT(disp) suggests delayed myocyte repolarisation on the cellular level, rather than temporal and spatial heterogeneity in the myocardial wall.
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Affiliation(s)
- Stig Hansen
- Department of Clinical Physiology, 239, H:S Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark
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Kosar F, Ates F, Sahin I, Karincaoglu M, Yildirim B. QT interval analysis in patients with chronic liver disease: a prospective study. Angiology 2007; 58:218-24. [PMID: 17495272 DOI: 10.1177/0003319707300368] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In previous studies, it has been shown that QT interval prolongation is related to an increased mortality rate in chronic liver disease (CLD). But QT dispersion (QTd) and its clinical significance in CLD has not been well studied. The objectives of this study were to investigate the relation between QTd and severity of the disease and determine its prognostic value in cirrhotic patients. Thirty-three consecutive patients with cirrhosis and 35 sex- and age-matched healthy subjects were studied. QT intervals and QT dispersions were measured on admission, and all intervals were corrected for heart rate according to Bazett's formula. The authors analyzed the potential relationship between QT parameters and the disease severity according to Child-Pugh classification and compared these values between survivors and nonsurvivors after a 3-year follow-up. Child-Pugh classification is used to assess liver function in cirrhosis. Corrected QT (QTc) prolongations were found in 32% of patients with cirrhosis and 5.7% of the healthy controls (p <0.001). The prevalence of increased (>70 ms) corrected QT dispersion (QTcd) was 45% in patients with cirrhosis. According to Child-Pugh criteria: QTd, maximum QT interval (QTmax), corrected QTmax (QTcmax), and QTcd in class C were significantly higher than those of class A and B (p <0.05, for all comparison). But there was no significant difference between class A and B in QTmax, QTcmax, QTd, and QTcd. There were 10 (30%) deaths from all causes during 3-year follow-up in the study group. Cox regression analysis showed that QTd and QTcd were better mortality indicators than QTmax and QTcmax, and Child's classification was the best predictor for mortality among all variables. In conclusion, QT dispersion and corrected QT dispersion parameters were better mortality indicators than other QT interval parameters and also may give additional prognostic information in patients with chronic liver disease.
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Affiliation(s)
- Feridun Kosar
- Department of Cardiology, Inonu University, Faculty of Medicine, Malatya, Turkey.
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