Cirrhotic Cardiomyopathy Research Articles

Synergetic Effect of Lupeol and Naringin Against Bile Duct Ligation Induced Cardiac Injury in Rats via Modulating Nitrite Level (eNos) and NF-kB /p65 Expression.

Cardiac dysfunction such as cirrhotic cardiomyopathy is more common in liver cirrhosis related disorders including primary biliary cholangitis or biliary cirrhosis and primary sclerosing cholangitis. Bile duct ligation (BDL) is an effective model of biliary cholestasis, producing oxidative damage and fibrosis. This research was designed to evaluate the effect of Lupeol and Naringin and its combination on bile duct ligation induced cardiac injury in rats. For pharmacological evaluation, rats were randomly divided into seven groups; intrahepatic cholestasis induced by ligation of the bile duct might lead to cirrhotic cardiomyopathy. The results were analyzed by physical, biochemical and histological examination. The Lupeol (100 mg/kg, p.o.), Naringin (100 mg/kg, p.o.) and its combination (100 mg/kg each) treated group significantly improved physical infarct size, biochemical (Nitrite, SOD, CAT, and GSH) and histological (heart tissue- mitochondrial function/integrity and fibrosis) alterations occurs due to BDL-ligation. This study was concluded that oral administration of Lupeol, Naringin, and its combination has a curative potential against BDL-induced cardiac injury in rats by reducing oxidative stress and inflammatory reactions, resulting in reduced heart necrosis/myocardial infarction and increased myocardial activity. It also inhibits cardiac damage in the rat heart, these effects may be linked to the NO level (eNOS) is increased and the inactivation of the NF-kB-p65 expression pathways.This study also provides new insights into the development of lupeol and Naringin combination that can be used as supportive therapy for cardiovascular diseases.

Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats

AimsLiver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. Materials and methodsBile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2–related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. Key findingsThe chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. SignificanceAtorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.

Left atrial dysfunction is an independent predictor of mortality in patients with cirrhosis treated by transjugular intrahepatic portosystemic shunt.

The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long‐term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two‐dimensional speckle‐tracking echocardiography (2D‐STE). A total of 129 TIPS candidates (mean ± SD, 61 ± 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain ≤35%, based on a previously suggested cut‐off value. The outcome was all‐cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain ≤35%) was noted in 67 (52%) patients. After a median follow‐up of 36 months (range, 12–80), 65 (50%) patients died. All‐cause mortality rates increased along worse grades of LVDD (log‐rank p = 0.007) and with LA dysfunction (log‐rank p = 0.001). On multivariable Cox regression analysis, Model for End‐Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all‐cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta χ 2 = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D‐STE is independently associated with all‐cause mortality in patients with cirrhosis treated by TIPS.

Cirrhotic Cardiomyopathy: The Interplay Between Liver and Heart.

Cardiac vascular dysfunction was described years ago in alcohol-associated liver cirrhosis and recently became known as cirrhotic cardiomyopathy (CCM) in 2005. Cirrhotic cardiomyopathy is a specific cardiac dysfunction estimated to be prevalent in half of the liver cirrhosis patient population; it comprises a triad of impaired myocardial contractile responses to stress (systolic dysfunction), inadequate ventricular relaxation, and electrophysiological abnormalities. This review describes the various pathophysiological mechanisms connecting liver cirrhosis to the alterations seen in CCM and briefly mentions the role of the cardiovascular system in connecting the pathophysiology of hepatorenal syndrome (HRS). Insertion of the transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation exacerbates the underlying cardiac dysfunction leading to signs and symptoms of heart failure. This article also focuses on the clinical importance of diagnosing CCM and the limitations existing around traditional diagnostic criteria based on transmitral flow parameters. It highlights newer parameters proposed by the Cirrhotic Cardiomyopathy Consortium to obtain a diagnosis of CCM. Liver transplantation is the only treatment available to cure CCM.

Tissue doppler imaging assessment for left ventricular systolic and diastolic function in patients with different grades of liver cirrhosis

Background: Chronic cardiac disease known as cirrhotic cardiomyopathy dysfunction in cirrhotic patients characterised by altered diastolic relaxation and/or impaired contractile reactivity to stress in the absence of other recognised cardiac diseases.. Aim and objectives: The purpose of the study was to evaluate tissue Doppler the left ventricle's systolic and diastolic characteristics performance in patients with liver cirrhosis. Subjects and methods: Al-Hussien Hospital, Al-Azhar University, did this cross-sectional case-control study, The study included 75 patients with liver cirrhosis and 25 healthy participants. There were four groups created from the study populations: 25 healthy volunteers make up the control group. Patients in Group 1 have Child A liver cirrhosis, while those in Group 2 have Child B cirrhosis. Group 2., Group 3, which consists of patients with Child C liver cirrhosis. Results: A statistically significant higher mean value in patients group compared to control group according to MPI PWD, MPI TDI, MV E/É ratio, DT (ms) and IVRT (ms) with p-value (p<0.05 significant); The average values of the EF by Simpson, Average S wave, and EF by M mode all differed significantly.

Chronotropic incompetence in end-stage liver disease.

BackgroundCirrhosis causes alterations in the cardiovascular and autonomic nervous systems and leads to cirrhotic cardiomyopathy (CCM). CCM is defined as cardiac dysfunction characterized by an impaired systolic responsiveness to stress or exercise, and/or impaired diastolic function, as well as electrophysiological abnormalities, including chronotropic incompetence (CI), in the absence of other known cardiac disease. CI is a common feature of autonomic neuropathy in cirrhosis. The aim of the study is to assess the role of cardiac exercise stress test in the diagnosis of CCM.MethodsThe analysis included 160 end-stage liver disease (ESLD) patients who underwent a cardiac exercise stress test prior to the orthotopic liver transplantation. CI was defined as the inability to achieve the heart rate reserve (HRR). Pertaining to the therapy with beta-blockers: 80% of HRR was achieved in patients not taking beta-blockers and 62% in patients taking beta-blockers.ResultsIn the analyzed population, 68.8% of patients met the criteria for CI. CI was more frequent in the more severe ESLD (with a higher MELD score and in a higher Child-Pugh class). In comparison to the viral hepatitis and other etiologies of ESLD, patients with alcoholic cirrhosis had a significantly lower rest heart rate (HR), lower maximal HR, lower median achieved percentage of maximal predicted HR (MPHR), a smaller percentage of patients achieved ≥ 85% of MPHR and a lower heart rate reserve. No significant relationship between the survival of OLT recipients and presence of chronotropic incompetence regarding to class of Child-Pugh scale, MELD score and etiology of ESLD were found.ConclusionsThe prevalence of CI is higher among liver transplant candidates than previously described. The altered chronotropic response may differ in regard to the severity of liver disease correlating with both the Child-Pugh and MELD scores, however CI does not seem to influence the long-term survival post OLT. Exercise stress test is a reliable, safe and useful tool for the diagnosis of CCM in liver transplant candidates and should be included in the standard cardiovascular assessment prior to OLT.

Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels.

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis.Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05.Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE.Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

Study of cardiovascular dysfunction in chronic liver disease in a tertiary care hospital in eastern India

Background: Chronic liver disease (CLD) exhibits characteristic hemodynamic changes along with pathological changes in the myocardium. Compensated by the decreased systemic vascular resistance, overt heart failure is usually not seen, and thus cardiac pathology is frequently overlooked. Aims and Objectives: The objectives of the study were to study the presence, types, and severity of cardiovascular (CV) dysfunction in patients of CLD. Materials and Methods: An observational cross-sectional study on 50 patients of CLD at Calcutta National Medical College and Hospital, with all relevant investigations. Results: Out of a sample of 50 patients, of which 14.3% were mild, 34.3% moderate and 51.4% severe CLD (by Child-Pugh Class), 28.6% had a high normal heart rate (90 to 100/min), 45.7% had increased stroke volume index, and 42.9% increased cardiac index, reflecting hyperdynamic circulation. In 42% cases, left ventricular ejection fraction was increased more than 65%, reflecting hyperdynamic circulation, but decreased <55% in 23% cases, which may be an indicator of cirrhotic cardiomyopathy. Ejection fraction is significantly (P=0.016) increased after paracentesis in 33.3% patients, reflecting the mechanical effect of ascites on cardiac function. Diastolic dysfunction was present in 60% (P=0.012) and left ventricular mass index was increased in 45.7% cases. All the parameters correlated with increasing Child-Pugh Class severity of CLD. Conclusion: A high level of awareness is needed to take into account the presence of CV dysfunction and cirrhotic cardiomyopathy in patients of CLD and predict the risk of adverse cardiac events. Specific treatment modalities need further study to improve prognosis in these patients.

Infuence of cirrhotic cardiomyopathy defined according to the new multidisciplinary diagnostic criteria on overall mortality among cirrhotic patients

Infuence of cirrhotic cardiomyopathy defined according to the new multidisciplinary diagnostic criteria on overall mortality among cirrhotic patients

OS012 - Impact of cirrhotic cardiomyopathy and severity of liver cirrhosis on the development of acute kidney injury

OS012 - Impact of cirrhotic cardiomyopathy and severity of liver cirrhosis on the development of acute kidney injury

Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity?

AimsPatients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis.MethodsThirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility.ResultsNineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02).ConclusionWe found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility.

Cardiac dysfunction in patients with end-stage liver disease, prevalence, and impact on outcome: a comparative prospective cohort study

BackgroundWithout firm diagnostic criteria, the exact prevalence of cirrhotic cardiomyopathy still remains unknown. Its estimation is rather a difficult task as the disease is generally latent and shows itself only when the patient is subjected to overt stress such as body position changes, exercise, drugs, hemorrhage, and surgery. In this study, we aim to assess cardiac dysfunction in patients with end-stage liver disease, study the correlation between cardiac dysfunction and Child-Pugh classification of patients with liver cell failure, and study the prevalence and impact of cardiac dysfunction on the clinical outcome of patients with child B and child C liver disease.ResultsDiastolic dysfunction was more prevalent among the patients’ group (p < 0.001). It was absent in 28 (70%) of control group, with grade 1 diastolic dysfunction in 12 (30%). Only one patient (2.5%) had no diastolic dysfunction, 21 patients (52.5%) had grade 1 diastolic dysfunction, 12 (30%) patients had grade 2 diastolic dysfunction, and 6 patients (15%) had grade 3 diastolic dysfunction. QTc interval was significantly prolonged in the patients’ group when compared to controls (p < 0.001). Echocardiographic parameters and QTc interval were comparable in child B and child C patients. All patients were followed up for a period of 3 months. Sixteen of 40 patients died in this period of time. Only child classification was found to significantly predict mortality, and patients with child C liver cirrhosis had worse survival when compared to patients with child B liver cirrhosis.ConclusionMost of the patients had cardiac dysfunction, mainly diastolic dysfunction (87.5%). The study detected the prevalence of diastolic dysfunction among end-stage liver disease when measuring E/É using TDI which proved to be more accurate than E/A ratio. Diastolic dysfunction is proved to be the most sensitive parameter in the diagnosis of cirrhotic cardiomyopathy, being the most parameter affected early. No correlation was found between cardiac dysfunction and the severity of hepatic illness, but the severity of hepatic illness affects the outcome rather than cardiac dysfunction.

Cirrhotic cardiomyopathy: Appraisal of the original and revised criteria in predicting posttransplant cardiac outcomes.

Cardiovascular disease (CVD) significantly contributes to morbidity and mortality after liver transplantation (LT). Cirrhotic cardiomyopathy (CCM) is a risk factor for CVD after transplant. CCM criteria were originally introduced in 2005 with a revision proposed in 2020 reflecting echocardiographic technology advancements. This study assesses the two criteria sets in predicting major adverse cardiac events (MACE) after transplant. This single-center retrospective study reviewed adult LT recipients between January 1, 2009, and December 31, 2018. Patients with insufficient pre-LT echocardiographic data, prior ischemic heart disease, portopulmonary hypertension, or longitudinal care elsewhere were excluded. The primary composite outcome was MACE (arrhythmia, heart failure, cardiac arrest, and/or cardiac death) after transplant. Of 1165 patients, 210met the eligibility criteria. CCM was present in 162 patients (77%) per the original criteria and 64 patients (30%) per the revised criteria. There were 44 MACE and 31 deaths in the study period. Of the deaths, 38.7% occurred secondary to CVD. CCM defined by the original criteria was not associated with MACE after LT (p=0.21), but the revised definition was significantly associated with MACE (hazard ratio [HR], 1.93; 95% confidence interval, 1.05-3.56; p=0.04) on multivariable analysis. Echocardiographic variable analysis demonstrated low septal e' as the most predictive variable for MACE after LT (HR, 3.45; p<0.001). CCM, only when defined by the revised criteria, was associated with increased risk for MACE after LT, validating the recently revised CCM definition. Abnormal septal e', reflecting impaired relaxation, appears to be the most predictive echocardiographic criterion for MACE after LT.

Prevalence of Cardiac Dysfunction in Cirrhosis and Its Relation With Meld Score

Background: Cardiac structural and functional abnormalities have been described in patients of liver cirrhosis. The constellation of these abnormalities is termed as cirrhotic cardiomyopathy (CCM) and its prevalence remains unknown, mostly because the disease is latent and shows itself when the patient is subjected to stress. This study was designed to evaluate the prevalence of cardiac dysfunction in patients of liver cirrhosis and to analyze its relation with model for end-stage liver disease (MELD) score. Methods: Hundred patients of liver cirrhosis were enrolled for the study and divided into 3 groups according to MELD score: ≤9, 10-19, and ≥20. All study participants underwent detailed cardiac assessment with Doppler echocardiography. Prevalence of cardiac dysfunction and its relation with MELD score was determined. Results: Prevalence of CCM and diastolic dysfunction (DD) was 48% and 30%, respectively. A total of 82%, 59%, and 50% patients had prolonged corrected QT interval (QTc), isovolumic relaxation time (IVRT), and deceleration time (DT), respectively. Prevalence of CCM, DD and prolonged QTc, IVRT, and DT had significant correlation with MELD score ( P &lt; .05). Conclusion: Patients with cirrhosis had impaired cardiac function, mainly present as CCM and DD, and the extent of dysfunction was correlated with the MELD score. Hence, MELD scoring system can be used to predict risk of occurrence of cardiac dysfunction in cirrhosis.

The challenges of ascites management: An Indian perspective.

Content available: Author Interview and Audio Recording.

Cardiovascular manifestation of end-stage liver disease and perioperative echocardiography for liver transplantation: anesthesiologist's view.

Liver transplantation (LT) is the curative therapy for decompensated cirrhosis. However, anesthesiologists can find it challenging to manage patients undergoing LT due to the underlying pathologic conditions of patients with end-stage liver disease and the high invasiveness of the procedure, which is frequently accompanied by massive blood loss. Echocardiography is a non-invasive or semi-invasive imaging tool that provides real-time information about the structural and functional status of the heart and is considered to be able to improve outcomes by enabling accurate and detailed assessments. This article reviews the pathophysiologic changes of the heart accompanied by cirrhosis that mainly affect hemodynamics. We also present a comparative review of the diagnostic criteria for cirrhotic cardiomyopathy published by the World Congress of Gastroenterology in 2005 and the Cirrhotic Cardiomyopathy Consortium in 2019. This article discusses the conditions that could affect hemodynamic stability and postoperative outcomes, such as coronary artery disease, left ventricular outflow tract obstruction, portopulmonary hypertension, hepatopulmonary syndrome, pericardial effusion, cardiac tamponade, patent foramen ovale, and ascites. Finally, we cover a number of intraoperative factors that should be considered, including intraoperative blood loss, rapid reaccumulation of ascites, manipulation of the inferior vena cava, post-reperfusion syndrome, and adverse effects of excessive fluid infusion and transfusion. This article aimed to summarize the cardiovascular manifestations of cirrhosis that can affect hemodynamics and can be evaluated using perioperative echocardiography. We hope that this article will provide information about the hemodynamic characteristics of LT recipients and stimulate more active use of perioperative echocardiography.

Pathogenic Mechanisms Underlying Cirrhotic Cardiomyopathy.

Cardiac dysfunction associated with cirrhosis in the absence of preexisting heart disease is a condition known as cirrhotic cardiomyopathy (CCM). Cardiac abnormalities consist of enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM may contribute to cardiovascular morbidity and mortality after liver transplantation and other major surgeries, and also to the pathogenesis of hepatorenal syndrome. The underlying mechanisms of CCM are poorly understood and as such medical therapy is an area of unmet medical need. The present review focuses on the pathogenic mechanisms responsible for development of CCM. The two major concurrent mechanistic pathways are the inflammatory phenotype due to portal hypertension, and protein/lipid synthetic/metabolic defects due to cirrhosis and liver insufficiency. The inflammatory phenotype arises from intestinal congestion due to portal hypertension, resulting in bacteria/endotoxin translocation into the systemic circulation. The cytokine storm associated with inflammation, particularly TNFα acting via NFκB depresses cardiac function. They also stimulate two evanescent gases, nitric oxide and carbon monoxide which produce cardiodepression by cGMP. Inflammation also stimulates the endocannabinoid CB-1 pathway. These systems inhibit the stimulatory beta-adrenergic contractile pathway. The liver insufficiency of cirrhosis is associated with defective synthesis or metabolism of several substances including proteins and lipids/lipoproteins. The protein defects including titin and collagen contribute to diastolic dysfunction. Other protein abnormalities such as a switch of myosin heavy chain isoforms result in systolic dysfunction. Lipid biochemical changes at the cardiac sarcolemmal plasma membrane result in increased cholesterol:phospholipid ratio and decreased membrane fluidity. Final common pathway changes involve abnormal cardiomyocyte intracellular ion kinetics, particularly calcium. In conclusion, cirrhotic cardiomyopathy is caused by two pathways of cellular and molecular dysfunction/damage due to hepatic insufficiency and portal hypertension.

Living Donor Liver Transplantation in a Cohort of Recipients With Left Ventricular Systolic Dysfunction

Data on feasibility, management, and outcomes of liver transplantation (LT) in patients with pre-existing left ventricular systolic dysfunction (LVSD), severe coronary artery disease (CAD) or cirrhotic cardiomyopathy (CCM) is scarce. We reviewed outcomes of living donor liver transplantation (LDLT) in recipients with LVSD (ejection fraction [EF] < 50%) from our series of 1946 LDLT's performed between July 2010 and July 2018. LVSD was detected in 12 male patients with a mean age, BMI and MELD of 52 ± 9 years, 25 ± 5kg/m2, and 19±4 respectively. Out of these, 6 patients had CAD (2 with previous coronary artery bypass graft, 1 following recent percutaneous transluminal coronary angioplasty, 2 post myocardial infarction, 1 noncritical CAD), and 6 had CCM. The EF ranged from 25% to 45%. Ethanol was the predominant underlying etiology for cirrhosis (50%). During LDLT, 2 patients developed ventricular ectopic rhythm and were managed successfully with intravenous lidocaine. Stress cardiomyopathy manifested in 3 patients post operatively with decreased EF, of which 2 improved, while 1 needed IABP support and succumbed to multiorgan failure on 8th postoperative day (POD). Another patient died on POD30 due to septic shock. Both these patients had higher MELD scores (actual MELD), extremes of BMI (17.3and 35.8kg/m2) and were diabetic. There were no long-term cardiac deaths. The 1-year, and 5-year survival were 75%, and 66%, respectively. Among potential LT recipientswith LVSD, those with stable CAD and good performance status, and well optimized CCM patients may be considered for LDLT after careful risk stratification in experienced centers.

Common variants in AGR1 genes contributed to the risk and traits of cirrhotic cardiomyopathy in the Han Chinese population.

Aim: This study aimed to determine the association between polymorphisms of the ARG1 gene and the risk and traits of cirrhotic cardiomyopathy (CCM). Methods: A total of 468 CCM and 1012 cirrhosis patients were enrolled, and 12 single-nucleotide polymorphisms (SNPs) in the ARG1 gene were genotyped. Differences in genotype, allele and haplotype frequencies of the SNPs between the CCM and cirrhosis groups were analyzed by chi-square test. Correlations of the genotypes of SNPs and representative traits of liver and heart function were performed using linear regression analysis. Results: SNPs rs2781666 and rs2781667 were associated with the risk of CCM in both dominant and additive inheritance models. The GG genotype frequency of rs2781666 and CC genotype frequency of rs2781667 were lower in the CCM group than in the cirrhosis group. The G-C haplotype frequency of the block consisting of rs2781666 and rs2781667 was higher and the T-T haplotype frequency was lower in CCM patients than in cirrhosis patients. SNP rs2781666 was associated with the alanine transaminase level, and rs2781667 was associated with the ARG1 level and left atrial diameter. Conclusion: SNPs rs2781666 and rs2781667 in the ARG1 gene were associated with susceptibility to and traits of CCM in the Han Chinese population.

Potential cardioprotective influence of bupropion against CCl4-triggered cirrhotic cardiomyopathy

Bupropion, an atypical anti-depressant and smoking cessation aid, attenuates complications arising from the activation of inflammatory and oxidative pathways. In this study, the effect of bupropion on an inflammatory and oxidative condition induced by carbon tetrachloride (CCl 4 ) namely cirrhotic cardiomyopathy (CCM) was investigated in rats. CCM was induced by intraperitoneal injection of CCl 4 (0.4 g/kg, i.p.). Bupropion was treated orally at doses 30 and 60 (mg/kg, p.o.) for 8 weeks. CCl 4 treatment significantly lowered hepatic antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) while enhanced Malondialdehyde (MDA). Elevations in serum nitric oxide (NO) metabolites nitrite/nitrate, and cardiac tumor necrosis factor alpha (TNF-α) and interleukin 1-beta (IL-1β) levels were observed. Cirrhosis also decreased contractility in response to isoproterenol (10 −10 to 10 −5 M). The spleen weight and intrasplenic pressure increased and QTc, QRS and RR intervals prolonged. Pathological damages in the liver for example focal necrosis, fibrosis and the hepatic blocking increased. On the other hand, bupropion increased GSH, CAT and SOD and lowered MDA. Bupropion reduced NO metabolites and TNF-α levels and decreased IL-1β. The cardiac contractile force improved at maximal effect (Rmax) 10 -5 M by bupropion. The intrasplenic pressure was reduced by bupropion. Bupropion reduces QTc, QRS and RR intervals and the liver tissue damages. Bupropion played a cardioprotective role reducing inflammatory and oxidative factors. It may recover the impairment of cardiac contractility and hyperdynamic condition in CCM, and this effect could be mediated at least in part by a NO-dependent mechanism.