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Purpose of Review: Cirrhotic cardiomyopathy (CCM) is a clinical entity that reflects the maladaptive responses of the heart to advanced chronic liver disease. With the recent developments in this field, this review details the most up to date knowledge about the pathogenesis of CCM, recent changes in its diagnostic criteria, and its clinical relevance. Recent Findings: Advances in echocardiographic techniques over the last several years and recent research have highlighted the high prevalence of CCM approaching 35% and demonstrated adverse impact of CCM on clinical outcomes following transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation (LT). Summary: The diagnostic criteria for cirrhotic cardiomyopathy have evolved with advancements in echocardiographic techniques allowing for precise and perhaps timely identification of those with subclinical cardiac impairment. CCM increases the risk for adverse outcomes in patients with cirrhosis and liver transplant recipients. Future studies are needed to identify subgroups of patients at highest risk for cirrhotic cardiomyopathy, the frequency and duration of monitoring for those with CCM, and potential therapeutics for patients with cirrhosis and liver transplant who have been diagnosed with cirrhotic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%–70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute‐on‐chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research. [ABSTRACT FROM AUTHOR]

Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear. Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNTNT5E- mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured. Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A. Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background: Cirrhotic cardiomyopathy, an intricate and multifaceted complication of end-stage liver disease, manifests as systolic and diastolic dysfunction in patients without previously diagnosed cardiac disease. Our study aims to investigate the prevalence of systolic and diastolic function in patients with cirrhotic cardiomyopathy in our region. Methods: We conducted a cross-sectional study on 68 patients with established cirrhosis, and no overt cardiac manifestations, who consequently underwent 2D echocardiography to quantify systolic and diastolic dysfunction, as defined by the 2019 Cirrhotic Cardiomyopathy Consortium. The severity of cirrhosis was determined using various validated scoring systems. Results: A total of 19 out of 68 (28%) had systolic dysfunction, while 6/68 (9%) had evidence of diastolic dysfunction. Overall prevalence of cirrhotic cardiomyopathy was 23/68 (34%), and the presence of hepatitis C was strongly associated with systolic dysfunction with p-value of 0.007. However, it was not significantly associated with diastolic dysfunction, p-value = 0.59. Logistic regression analysis did not show any significant association between cardiac dysfunction and the severity of liver cirrhosis, as assessed by Child–Pugh, MELD, ALBI, PALBI, portal hypertension, and FIB-4 score (R2 = 3.66, F (13, 39) = 1.33, p = 0.234). Conclusion: Our study reveals a remarkable prevalence of cirrhotic cardiomyopathy, which despite being a frequently occurring phenomenon often goes unrecognized. Lack of correlation with the severity of liver cirrhosis, based on currently available scoring system, suggests either a still poorly understood pathological mechanism or requires the development of a new validated reliable scoring system through multi-center longitudinal studies. [ABSTRACT FROM AUTHOR]

Abstract Background Cirrhotic cardiomyopathy, an intricate and multifaceted complication of end-stage liver disease, manifests as systolic and diastolic dysfunction in patients without previously diagnosed cardiac disease. Our study aims to investigate the prevalence of systolic and diastolic function in patients with cirrhotic cardiomyopathy in our region. Methods We conducted a cross-sectional study on 68 patients with established cirrhosis, and no overt cardiac manifestations, who consequently underwent 2D echocardiography to quantify systolic and diastolic dysfunction, as defined by the 2019 Cirrhotic Cardiomyopathy Consortium. The severity of cirrhosis was determined using various validated scoring systems. Results A total of 19 out of 68 (28%) had systolic dysfunction, while 6/68 (9%) had evidence of diastolic dysfunction. Overall prevalence of cirrhotic cardiomyopathy was 23/68 (34%), and the presence of hepatitis C was strongly associated with systolic dysfunction with p-value of 0.007. However, it was not significantly associated with diastolic dysfunction, p-value = 0.59. Logistic regression analysis did not show any significant association between cardiac dysfunction and the severity of liver cirrhosis, as assessed by Child–Pugh, MELD, ALBI, PALBI, portal hypertension, and FIB-4 score (R 2 = 3.66, F (13, 39) = 1.33, p = 0.234). Conclusion Our study reveals a remarkable prevalence of cirrhotic cardiomyopathy, which despite being a frequently occurring phenomenon often goes unrecognized. Lack of correlation with the severity of liver cirrhosis, based on currently available scoring system, suggests either a still poorly understood pathological mechanism or requires the development of a new validated reliable scoring system through multi-center longitudinal studies.

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment. [ABSTRACT FROM AUTHOR]

Cardiac morphology and function, which are conventionally evaluated by echocardiography, are often abnormal in decompensated cirrhosis. We aimed to evaluate the association of echocardiography-related parameters with prognosis in cirrhosis. This retrospective study included 104 decompensated cirrhotic patients, in whom cardiac structure and function were measured by echocardiography, including mitral inflow early diastolic velocity/mitral inflow late diastolic velocity (E/A), left atrium diameter, left ventricular end-diastolic dimension, interventricular septal thickness, left ventricular posterior wall thickness, right atrial transverse diameter, right atrial longitudinal diameter, right ventricular dimension (RVD), stroke volume, cardiac output, left ventricular ejection fraction, and fractional shortening. Cox regression and competing risk analyses and Kaplan-Meier and Nelson-Aalen cumulative risk curves were used to evaluate their associations with further decompensation and death in cirrhotic patients, if appropriate. Lower RVD was a predictor of further decompensation in Cox regression (adjusted by Child-Pugh score: p = 0.138; adjusted by MELD score: p = 0.034) and competing risk analyses (p = 0.003), and RVD ≤17 mm was significantly associated with higher cumulative incidence of further decompensation in Kaplan-Meier (p = 0.002) and Nelson-Aalen cumulative risk curves (p = 0.002). E/A ≤ 0.8 was a significant predictor of death in Cox regression (adjusted by Child-Pugh score: p = 0.041; adjusted by MELD score: p = 0.045) and competing risk analyses (p = 0.024), and E/A ≤ 0.8 was significantly associated with higher cumulative incidence of death in Kaplan-Meier (p = 0.023) and Nelson-Aalen cumulative risk curves (p = 0.024). Other echocardiography-related parameters were not significantly associated with further decompensation or death. RVD and E/A may be considered for the prognostic assessment of decompensated cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of prolonged QTc (corrected QT) interval in patients. With decompensated chronic liver disease (DCLD) in a tertiary care hospital of Gadap town, Sindh. Methods: This cross-sectional study was conducted from 1st January 2022 to 31 December 2022 at the Department Of Medicine, Baqai Medical University, Karachi. All partial and fully decompensated Cirrhotic patients aged 25 to 75 years regardless of sex, diagnosed based on history, physical Examination and ultrasonography findings, who were admitted to our medical ward, were included using a non-probability convenience sampling technique. Pregnant females, patients with other major co-morbid illnesses, electrolyte imbalances and those on medications affecting QTc interval were excluded. All patients meeting inclusion criteria were enrolled for a 12 lead ECG (three serial recordings each), from which QT, R-R interval, as well as QTc, were calculated. Data entry and analysis were performed using SPSS version 20. Categorical variables were described using frequency and percentages whereas continuous variables were summarized using mean and standard deviation. Results: Out of 196 participants with decompensated liver disease included in the study, 59 (30.1%) participants were found to have prolonged QTc. Age, Child–Turcotte–Pugh (CTP) class and Bilirubin of the patients were significantly associated with QTc prolongation. Conclusion: Prolonged QTc interval, a marker of cirrhotic cardiomyopathy, is a common occurrence in patients with decompensated chronic liver disease. The risk of developing prolonged QTc interval increases with advanced age and progressive liver disease. [ABSTRACT FROM AUTHOR]

The systemic sequelae of chronic liver disease (CLD) may be due to portal hypertension and shunting, malnutrition, and/or a low grade inflammatory state. This article will focus on the consequences of chronic liver disease affecting extrahepatic organs. Portal hypertension underlies many systemic complications of CLD. Aside from varices and ascites, portal hypertension may cause both hepatopulmonary syndrome and portopulmonary hypertension leading to respiratory compromise. Cardiomyopathy may also occur secondary to end stage liver disease. Hepatorenal syndrome is also well recognised and hepatic encephalopathy is a consequence of the effect of liver dysfunction on the brain. Compromise of the immune system is well described in end-stage liver disease leading to sepsis and its consequences. Bony disease including osteoporosis and hepatic arthropathy may both be seen in children with CLD. CLD may be asymptomatic initially but then complications may present as the disease progresses. Furthermore, systemic effects of end stage liver disease may complicate liver transplant. These complications often present insidiously or at the time of acute decompensation. Thus, it is important that healthcare providers are vigilant when caring for children with CLD. This article outlines the secondary complications of CLD with an overview of the definition and diagnosis, pathophysiology, management and prognosis of each. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy (CCM) is characterized by elevated cardiac output at rest, an inability to further increase contractility under stress, and diastolic dysfunction. The diagnosis of CCM is crucial as it can lead to complications during liver transplantation. However, its recognition poses challenges with conventional echocardiography techniques. Speckle tracking echocardiography (STE), particularly global longitudinal strain (GLS), is a novel index that enhances the diagnostic efficacy of echocardiography for both ischemic and non-ischemic cardiomyopathies. GLS proves more sensitive in identifying early systolic dysfunction and is also influenced by advanced diastolic dysfunction. Consequently, there is an expanding scope for GLS utilization in cirrhotic cases, with newly updated diagnostic criteria for CCM incorporating GLS. Specifically, systolic dysfunction is now defined as either a left ventricular ejection fraction below 50% or an absolute GLS below 18%. However, conflicting data on GLS alterations in liver cirrhosis patients persist, as many individuals with advanced disease and a poor prognosis exhibit a hyperdynamic state with preserved or increased GLS. Consequently, the presence of CCM, according to the updated criteria, does not exhibit a significant association—in the majority of studies—with the severity of liver disease and prognosis. Furthermore, information on other indices measured with STE, such as left atrial and right ventricular strain, is promising but currently limited. This review aims to offer a critical assessment of the existing evidence concerning the application of STE in patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

Left ventricular diastolic dysfunction (LVDD) is a hallmark of cirrhotic cardiomyopathy and has been linked to a poorer quality of life and worse outcomes in patients with end-stage liver disease. Its impact on survival after a liver transplant (LT) is not known, especially when using current diagnostic criteria to define LVDD. We conducted a systematic review and meta-analysis of the current published literature on mortality after a LT in patients with LVDD. We searched for articles in PubMed, Scopus, EMBASE, Web of Science, and the COCHRANE Central database. We included cohort studies that compared post-transplant outcomes between cirrhotic patients with and without LVDD. Our primary outcome of interest was all-cause mortality after a LT in relation to the presence of LVDD per the 2016 American Society of Echocardiography criteria. A total of 1029 articles were screened during the selection process. Two studies included in the meta-analysis showed no significant difference in mortality, but there was high heterogeneity. A narrative review of other studies that classified diastolic function (DD) using different criteria was also performed, revealing an association with worse outcomes in these patients. High-quality prospective studies using current criteria are needed to confirm these findings.

Background: Cirrhosis is associated with numerous cardiac abnormalities, which include increased cardiac output, left ventricular diastolic dysfunction, increased wall thickness of cardiac chambers, and pulmonary arterial hypertension. Without further identified cardiac disorders, cirrhotic cardiomyopathy (CCM) is a chronic cardiac dysfunction with an impaired contractile reaction to stress stimuli, impeded diastolic relaxation, and electrophysiological anomalies with a prolonged QT interval. In chronic hepatic disease, echocardiography is a non-invasive method for detecting CCM. Aims and Objectives: The focus was to examine the link between cardiac dysfunction and conduction disturbances in cirrhosis individuals and the extent of the disorder. Materials and Methods: A case–control investigation was conducted at a Medical College. The research involved a cohort of 50 patients and an equal number of 50 healthy controls. The Child-Pugh (CP) Score was utilized to evaluate the degree of liver cirrhosis severity. Bazett’s formula was utilized to compute the QTc interval. The 2D echocardiography revealed the presence of diastolic dysfunction, as evidenced by the E/A ratio. Results: Of 50 patients, 37 (74%) were male, 13 (26%) were female, and the mean age of the patients was 51.76±9.89 years. The E/A ratio in the control group had a mean value of 1.10±0.19, whereas in the cases, it had a mean value of 0.94±0.20. A statistically significant relationship was observed between the control and cases, with a P-value of less than 0.0001. QTc interval between control with a mean value of 382.9±47.34 ms and cases with a mean value of 431.6±62.84 ms was found statistically significant with P

Left ventricular diastolic dysfunction (LVDD) is a hallmark of cirrhotic cardiomyopathy and has been linked to a poorer quality of life and worse outcomes in patients with end-stage liver disease. Its impact on survival after a liver transplant (LT) is not known, especially when using current diagnostic criteria to define LVDD. We conducted a systematic review and meta-analysis of the current published literature on mortality after a LT in patients with LVDD. We searched for articles in PubMed, Scopus, EMBASE,Web of Science, and the COCHRANE Central database. We included cohort studies that compared post-transplant outcomes between cirrhotic patients with and without LVDD. Our primary outcome of interest was all-cause mortality after a LT in relation to the presence of LVDD per the 2016 American Society of Echocardiography criteria. A total of 1029 articles were screened during the selection process. Two studies included in the meta-analysis showed no significant difference in mortality, but there was high heterogeneity. A narrative review of other studies that classified diastolic function (DD) using different criteria was also performed, revealing an association with worse outcomes in these patients. High-quality prospective studies using current criteria are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV‐GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV‐GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). Methods: One hundred and thirty‐five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D‐STE) were performed, and dual X‐ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. Results: LV‐GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV‐GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV‐GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3, p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. Conclusion: In our study, absolute LV‐GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end‐stage liver disease. [ABSTRACT FROM AUTHOR]

Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of cirrhotic cardiomyopathy in decompensated liver cirrhosis patients. Study Design: Descriptive, Cross-sectional. Setting: Department of Medicine, Bahawal Victoria Hospital, Bahawalpur. Period: February 2022 to August 2022. Material & Methods: Patients of either gender having age between 25-65 years with decompensated liver cirrhosis (duration >6 months) were analyzed. Demographic and clinical characteristics of each patient were recorded at the time of the inclusion. Then, echocardiography was done in each patient by consultant cardiologist and presence or absence of cirrhotic cardiomyopathy was noted. Results: In a total of 92 patients, 54 (58.7%) were male and 38 (41.3%) were female with male to female ratio as 1.4:1. The mean age was 42.92±8.72 years while 57 (61.96%) patients were aged between 25 to 45 years. The mean duration of disease was 8.52±2.48 months. The mean body mass index was 27.46±2.97 kg/m2. Diabetes was noted in 28 (30.4%) patients while 35 (38.0%) had hypertension. Frequency of cirrhotic cardiomyopathy in patients with decompensated liver cirrhosis was found in 38 (41.3%). Conclusion: This study concluded that the frequency of cirrhotic cardiomyopathy in decompensated liver cirrhosis patients is quite high. [ABSTRACT FROM AUTHOR]

Background: Cirrhosis is associated with numerous cardiac abnormalities, which include increased cardiac output, left ventricular diastolic dysfunction, increased wall thickness of cardiac chambers, and pulmonary arterial hypertension. Without further identified cardiac disorders, cirrhotic cardiomyopathy (CCM) is a chronic cardiac dysfunction with an impaired contractile reaction to stress stimuli, impeded diastolic relaxation, and electrophysiological anomalies with a prolonged QT interval. In chronic hepatic disease, echocardiography is a non-invasive method for detecting CCM. Aims and Objectives: The focus was to examine the link between cardiac dysfunction and conduction disturbances in cirrhosis individuals and the extent of the disorder. Materials and Methods: A case-control investigation was conducted at a Medical College. The research involved a cohort of 50 patients and an equal number of 50 healthy controls. The Child-Pugh (CP) Score was utilized to evaluate the degree of liver cirrhosis severity. Bazett's formula was utilized to compute the QTc interval. The 2D echocardiography revealed the presence of diastolic dysfunction, as evidenced by the E/A ratio. Results: Of 50 patients, 37 (74%) were male, 13 (26%) were female, and the mean age of the patients was 51.76±9.89 years. The E/A ratio in the control group had a mean value of 1.10±0.19, whereas in the cases, it had a mean value of 0.94±0.20. A statistically significant relationship was observed between the control and cases, with a P-value of less than 0.0001. QTc interval between control with a mean value of 382.9±47.34 ms and cases with a mean value of 431.6±62.84 ms was found statistically significant with P<0.0001. Conclusion: QTc prolongation and transmitral flow abnormality are markers of severe cardiac abnormality in patients with higher CP score in cirrhosis. Hence, recognition of such abnormalities in cirrhotic patients may prevent arrhythmogenic cardiovascular deaths in such patients. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.

Cirrhotic patients have hyperdynamic circulation and at-rest tachycardia, and agents that activate the sympathetic pathway, such as physical practice and pharmacologic stimulations, compared with the normal population, cannot cause enough increase in heartbeat, a condition known as cirrhotic cardiomyopathy. Concerning the presentation of 5-HT2 & 5-HT3 receptors in rat hearts, we used Ketanserin as a 5-HT2 receptor inhibitor & Tropisetron as a 5-HT3 receptor inhibitor to evaluate chronic therapeutic effects of 5-HT2 & 5-HT3 antagonists on the cardiac chronotropic response of cirrhotic rats to adrenergics. Cirrhosis was induced by surgical ligation of the bile duct in Male Wistar rats, and another group remained sham. A week after bile duct ligation or sham surgery, the subjects were given an intraperitoneal injection of either saline or Tropisetron (2 mg/kg). In other BDL & Sharm groups, the subjects were given an intraperitoneal injection of either saline or Ketanserin (6 mg/kg) every other 3 days in the last 3 weeks. Four weeks after bile duct ligation or sham surgery, the atria were isolated and chronotropic responsiveness to Isoproterenol was assessed using a standard organ bath. Our data showed that chronic treatment with Tropisetron (5-HT3 antagonist) in cirrhotic rats could decrease the cardiac chronotropic response. Chronic treatment with Tropisetron can cause a significant decrease in cardiac chronotropic response to Isoproterenol in healthy and cirrhotic rats, even lower than that in cirrhotic rats (without any special treatment). Chronic treatment with Ketanserin cannot change their impaired chronotropic response to Isoproterenol.

Background: We estimated the frequency of cirrhotic cardiomyopathy (CC) using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations, and to investigate the role of stress in unmasking latent cases of CC. Methods: Ninety consecutive patients were recruited. CC was evaluated using the Montreal, the American Society of Echocardiography 2009 criteria, and the 2019 modified criteria of the CCM consortium. A dobutamine stress test was also performed. Results: Left ventricular diastolic dysfunction (LVDD) was identified in 72 (80%), 36 (40%), and 10 (11.1%) patients based on the above criteria, respectively. None of the patients had right ventricular systolic dysfunction, either at rest or after stress. The dobutamine stress test revealed left systolic dysfunction in 4 (4.5%) patients. There was agreement among the 3 criteria that the presence of LVDD was not associated with the severity of liver disease, using Child-Pugh stage. However, patients with Child-B/C had longer QTc intervals (P=0.004), higher levels of brain natriuretic peptide (P=0.016), and greater echocardiographic E/e' ratio (P<0.001) and E/e'(s) (P=0.003), compared to Child-A patients, while a significant correlation was demonstrated between Child-Pugh score and E/e' (P<0.001), or E/e'(s) (P=0.002). Conclusions: The prevalence of LVDD seems to be lower than previously considered. Right ventricular function seems to remain unimpaired. A dobutamine stress uncovered only a small percentage of patients with left systolic dysfunction. Nevertheless, the aggravation of several sonographic variables during stress, particularly in Child-B/C patients, potentially indicates a higher risk for clinical heart failure during stressful invasive interventions. [ABSTRACT FROM AUTHOR]

Hepatic disease has a high prevalence globally and is one of the major causes of mortality. Patients with hepatic disease are also associated with an increased morbidity and mortality after surgery and anaesthesia. Several scoring systems have been used for perioperative risk stratifications. Impaired hepatic synthetic and metabolic functions create multiple pathophysiological pathways in the body, resulting in extensive extrahepatic manifestations. Therefore, careful preoperative assessment of various systems is warranted to assess different organ function, which allows patient optimization and careful perioperative planning. Liver is a major organ for drug metabolism, extra caution must be taken when choosing the type and dosage of medication. [ABSTRACT FROM AUTHOR]

Background: The prevalence of cirrhotic cardiomyopathy cannot be determined without diagnostic parameters. Its estimation is a challenging job because the disease is typically latent and only manifests when the patient experiences overt stress, such as changes in body position, exercise, drugs, hemorrhage, or surgery. The goal of this research is to evaluate cardiac dysfunction in patients with end-stage liver disease, examine the relationship between cardiac dysfunction and clinical outcomes in liver disease patients, and investigate the prevalence and effects of cardiac dysfunction. Results: The patients' group had a higher prevalence of diastolic impairment (p<0.001). Only one patient (5.2%) did not have any systolic dysfunction, while nine patients (47.3%) had grade 1 dysfunction, six (31.5%) had grade 2, and three (15.7%) had grade 3 dysfunction. When compared to controls, the patient group's QTc gap was significantly prolonged (p 0.001). Three months of follow-up were given to every subject. Of the 30 patients, 11 passed away during this time. The majority of patients suffer from cardiac failure, primarily diastolic dysfunction. Due to its early onset, diastolic dysfunction has been shown to be the most sensitive measure in the diagnosis of cirrhotic cardiomyopathy. No relationship between cardiac dysfunction and the severity of hepatic sickness was discovered, but the outcome is more affected by the severity of hepatic illness than cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM), initially described in 2005 and revised in 2019, is a source of MACE in patients after OLT. We sought to identify CCM-related predictors of MACE at one-year follow-up after OLT and assess for reversibility of CCM post-OLT. This is a retrospective study of adult patients who underwent OLT between 2009 and 2019. All patients had transthoracic echocardiography pre-and post-OLT. Patients with a left ventricular ejection fraction <50 % pre-OLT were excluded. MACE was defined as death, myocardial infarction, congestive heart failure hospitalization, or cardiac arrest. In total, 131 patients were included in this study, of whom 103 and 23 patients met the 2005 and 2019 criteria, respectively. During the follow-up period, 42 patients had MACE and these patients were more likely to have ascites (p = 0.003), hepatorenal syndrome (p = 0.019), and CCM per 2005 criteria (p = 0.023). There were no significant differences between pre-OLT CCM per 2019 criteria (19 % vs 17 %, p = 0.758) or MELD-Na score (21.24 vs 19.40, p = 0.166) for MACE post-OLT. Per the 2005 criteria, 35 of 103 patients recovered and these patients were less likely to have MACE post-OLT (p = 0.012). Per the 2019 criteria, 13 of 23 patients recovered post-OLT but this low number precluded further statistics. The 2005 Montreal criteria for CCM were an independent predictor of MACE at one-year follow-up post-OLT while the 2019 CCC criteria for CCM were not. In addition, the 2005 Montreal criteria were more prevalent when compared to 2019 CCC criteria. Finally, the 2005 Montreal criteria were reversible post-OLT 34 % of the time compared to the 2019 CCC criteria which were reversible 57 % of the time. [Display omitted] • Cirrhotic cardiomyopathy (CCM) predicts major adverse cardiac events (MACE). • CCM per 2005 criteria predicted MACE at 1 year, but CCM per 2019 criteria did not. • CCM is reversible in 34 % and 57 % of patients per 2005 and 2019 criteria respectively after orthotopic liver transplantation. • The 2005 criteria of CCM are more prevalent when compared to the 2019 criteria. [ABSTRACT FROM AUTHOR]

Cirrhotic patients have hyperdynamic circulation and at-rest tachycardia, and agents that activate the sympathetic pathway, such as physical practice and pharmacologic stimulations, compared with the normal population, cannot cause enough increase in heartbeat, a condition known as cirrhotic cardiomyopathy. Concerning the presentation of 5-HT2 & 5-HT3 receptors in rat hearts, we used Ketanserin as a 5-HT2 receptor inhibitor & Tropisetron as a 5-HT3 receptor inhibitor to evaluate chronic therapeutic effects of 5-HT2 & 5-HT3 antagonists on the cardiac chronotropic response of cirrhotic rats to adrenergics. Cirrhosis was induced by surgical ligation of the bile duct in Male Wistar rats, and another group remained sham. A week after bile duct ligation or sham surgery, the subjects were given an intraperitoneal injection of either saline or Tropisetron (2 mg/kg). In other BDL & Sharm groups, the subjects were given an intraperitoneal injection of either saline or Ketanserin (6 mg/kg) every other 3 days in the last 3 weeks. Four weeks after bile duct ligation or sham surgery, the atria were isolated and chronotropic responsiveness to Isoproterenol was assessed using a standard organ bath. Our data showed that chronic treatment with Tropisetron (5-HT3 antagonist) in cirrhotic rats could decrease the cardiac chronotropic response. Chronic treatment with Tropisetron can cause a significant decrease in cardiac chronotropic response to Isoproterenol in healthy and cirrhotic rats, even lower than that in cirrhotic rats (without any special treatment). Chronic treatment with Ketanserin cannot change their impaired chronotropic response to Isoproterenol. [ABSTRACT FROM AUTHOR]

Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy (CCM) is characterized by elevated cardiac output at rest, an inability to further increase contractility under stress, and diastolic dysfunction. The diagnosis of CCM is crucial as it can lead to complications during liver transplantation. However, its recognition poses challenges with conventional echocardiography techniques. Speckle tracking echocardiography (STE), particularly global longitudinal strain (GLS), is a novel index that enhances the diagnostic efficacy of echocardiography for both ischemic and non-ischemic cardiomyopathies. GLS proves more sensitive in identifying early systolic dysfunction and is also influenced by advanced diastolic dysfunction. Consequently, there is an expanding scope for GLS utilization in cirrhotic cases, with newly updated diagnostic criteria for CCM incorporating GLS. Specifically, systolic dysfunction is now defined as either a left ventricular ejection fraction below 50% or an absolute GLS below 18%. However, conflicting data on GLS alterations in liver cirrhosis patients persist, as many individuals with advanced disease and a poor prognosis exhibit a hyperdynamic state with preserved or increased GLS. Consequently, the presence of CCM, according to the updated criteria, does not exhibit a significant association—in the majority of studies—with the severity of liver disease and prognosis. Furthermore, information on other indices measured with STE, such as left atrial and right ventricular strain, is promising but currently limited. This review aims to offer a critical assessment of the existing evidence concerning the application of STE in patients with liver cirrhosis.

Cirrhotic patients often suffer from cirrhotic cardiomyopathy (CCM). Previous animal models of CCM were inconsistent concerning the time and mechanism of injury; thus, the temporal dynamics and cardiac vulnerability were studied in more detail. Rats underwent bile duct ligation (BDL) and a second surgery 28 days later. Cardiac function was assessed by conductance catheter and echocardiography. Histology, gene expression, and serum parameters were analyzed. A chronotropic incompetence (Pd31 < 0.001) and impaired contractility at rest and a reduced contractile reserve (Pd31 = 0.03, Pdob-d31 < 0.001) were seen 31 days after BDL with increased creatine (Pd35, Pd42, and Pd56 < 0.05) and transaminases (Pd31 < 0.001). A total of 56 days after BDL, myocardial fibrosis was seen (Pd56 < 0.001) accompanied by macrophage infiltration (CD68: Pgroup < 0.001) and systemic inflammation (TNFα: Pgroup < 0.001, white blood cell count: Pgroup < 0.001). Myocardial expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was increased after 31 (Pd31 < 0.001) and decreased after 42 (Pd42 < 0.001) and 56 days (Pd56 < 0.001). Caspase-3 expression was increased 31 and 56 days after BDL (Pd31 = 0.005; Pd56 = 0.005). Structural changes in the myocardium were seen after 8 weeks. After the second surgery (second hit), transient myocardial insufficiency with secondary organ dysfunction was seen, characterized by reduced contractility and contractile reserve. [ABSTRACT FROM AUTHOR]

Background: Cirrhotic patients who develop Spontaneous Bacterial Peritonitis (SBP), they most likely have cirrhotic cardiomyopathy, which is characterized by diminished contractility in response to stress despite a generally normal resting cardiac output. Objective: Patients who developed SBP can be assessed prognosticaly by electrocardiography and echocardiography together with scoring systems this was proposed in our study. Patients and Methods: Four hundred cirrhotic patients were included in our study admitted to our general ICU in Critical Care Medicine Department, Faculty of Medicine, Helwan University in the period from May 2020 to September 2022, all patients did not undergo transplant within the study duration and if any patients underwent liver transplant within one year of the last SBP episode were excluded. Patients were classified according to electrocardiographic parameters into low and high QTC and echo cardiographically with tissue Doppler into low and high E/E' Ratio with a cut off values > 480 ms for QTc and > 10 for E/E ratio. Results: Four hundred cirrhotic patients were classified into two groups according to the QTC and E/E' into low QTc and low E/E' group included 200 patients and high QTC and high E/E group included the other 200 patients. Higher QTC and higher E/E' were associated with increased in hospital acute kidney' injury, ICU mortality and 1 year mortality. Conclusion: Cirrhotic patients with SBP associated with high QTC and high E/E' are at high risk for acute kidney injury, ICU mortality and 1 year mortality, also, high QTC duration > 480 ms and high E/E' ratio of > 10 together with diabetes mellitus, left atrial diameter and left atrial volume, were independent parameters associated with increased mortality at 1-year followup. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis characterized by blunted cardiac contractile responses to stress and/or heart rate-corrected QT (QTc) interval prolongation. Caveolin-3 (Cav-3) plays a critical role in cardiac protection and is an emerging therapeutic target for heart disease. We investigated the protective role of cardiac-specific overexpression (OE) of Cav-3 in cirrhotic cardiomyopathy. Biliary fibrosis was induced in male Cav-3 OE mice and transgene negative (TGneg) littermates by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; 0.1%) for 3 wk. Liver pathology and blood chemistries were assessed, and stress echocardiography, telemetry, and isolated heart perfusion studies to assess adrenergic responsiveness were performed. Cav-3 OE mice showed a similar degree of hyperdynamic contractility, pulmonary hypertension, and QTc interval prolongation as TGneg mice after 3 wk of DDC diet. Blunted systolic responses were shown in both DDC-fed Cav-3 OE and TGneg hearts after in vivo isoproterenol challenge. However, QTc interval prolongation after in vivo isoproterenol challenge was significantly less in DDC-fed Cav-3 OE hearts compared with DDC-fed TGneg hearts. In ex vivo perfused hearts, where circulatory factors are absent, isoproterenol challenge showed hearts from DDC-fed Cav-3 OE mice had better cardiac contractility and relaxation compared with DDC-fed TGneg hearts. Although Cav-3 OE in the heart did not prevent cardiac alterations in DDC-induced biliary fibrosis, cardiac expression of Cav-3 reduced QTc interval prolongation after adrenergic stimulation in cirrhosis.NEW & NOTEWORTHY Prevalence of cirrhotic cardiomyopathy is up to 50% in cirrhotic patients, and liver transplantation is the only treatment. However, cirrhotic cardiomyopathy is associated with perioperative morbidity and mortality after liver transplantation; therefore, management of cirrhotic cardiomyopathy is crucial for successful liver transplantation. This study shows cardiac myocyte specific overexpression of caveolin-3 (Cav-3) provides better cardiac contractile responses and less corrected QT prolongation during adrenergic stress in a cirrhotic cardiomyopathy model, suggesting beneficial effects of Cav-3 expression in cirrhotic cardiomyopathy.

Amanuel Tadelle Department of Biomedical Sciences, Jimma University, Jimma City, EthiopiaCorrespondence: Amanuel Tadelle, Email newaman09@yahoo.com; amanuel.muluneh@ju.edu.etAbstract: The liver and the heart are related to each other in many aspects. So liver diseases affect the heart, and heart disease affects the liver. Hyperdynamic circulation, the inability of ventricular contractility, hypertrophy of the heart, and electrophysiological alteration of the heart (prolongation QT interval) are some complications of cirrhosis. The most known complication of cirrhosis in the heart is cirrhotic cardiomyopathy. The original definition of cirrhotic cardiomyopathy was stated at the World Congress of Gastroenterology (2015). It is characterized by cardiac alteration (both in structure and function) in patients with cirrhosis without previously known cardiac problems. The pathological mechanism of cirrhotic cardiomyopathy includes physiological and chemical changes in cardiac muscle cells and increased inhibition of cardiomyocytes. Beta-adrenergic receptors defect and desensitization, endogenous cannabinoids, and cardiomyocyte depressants (NO and inflammatory cytokines) decrease cardiac contractility. Forty to fifty percent of the patients with cirrhosis had QT interval prolongation. QT interval prolongation is the most known electrophysiological abnormality in cirrhotic cardiomyopathy. The main cause of QT interval prolongation is a receptor and ion channel defect and a change in membrane fluidity.Keywords: QT interval, cirrhosis, cirrhotic cardiomyopathy

Cirrhotic cardiomyopathy is a complication of cirrhosis which is still incompletely elucidated, being underdiagnosed due to the fact that it is generally latent at rest and it only manifests under stress; however, it can have a bad impact on the prognosis of cirrhotic patients. It is characterized by an impaired hemodynamic response to stress, a hyperdinamic circulatory status, systolic and diastolic dysfunction and electrophysiological impairments (most frequently, QT prolongation). The diagnosis is difficult because cirrhotic cardiomyopathy is usually asymptomatic at rest and the hemodynamic alterations together with the signs and symptoms of heart failure appear only in stressful conditions (effort, drugs, infections, hemorrhage, surgery etc.). The diagnosis is made by identifying systolic and diastolic dysfunction through stress echocardiography (effort, dobutamine etc.) or using myocardial strain imaging. In the absence of a proper diagnosis and treatment, cirrhotic cardiomyopathy can lead to severe complications such as heart failure, arrhythmias, hepatorenal syndrome or sudden death. At the moment, there is no standardized protocol for the treatment of cirrhotic cardiomyopathy, but the main therapeutic options are loop diuretics, aldosterone receptor antagonists, nonselective beta-blockers (in particular carvedilol) or angiotensin-converting enzyme inhibitors. Liver transplant significantly improves systolic and diastolic dysfunction and can reverse QT prolongation in some patients. However, there are limited studies that show a risk for cardiovascular complications after liver transplant. Therefore, a complex cardiovascular evaluation is recommended before and after the transplant. [ABSTRACT FROM AUTHOR]

Summary: Background: Atrial fibrillation (AF) is the most common arrhythmia and its management in cirrhosis can be challenging due to the altered hepatic metabolism of medications and increased risk of bleeding. Aims: To provide a comprehensive overview of the diagnosis, pathophysiology and management of AF in patients with cirrhosis from both a cardiology and a hepatology perspective. Methods: An extensive literature search was performed using the terms 'atrial fibrillation' and 'cirrhosis'. Guideline documents and consensus statements were explored. Results: The prevalence of AF in patients with cirrhosis ranges between 6.6% and 14.2%, while the incidence of new‐onset AF in the post‐operative period after liver transplant ranged between 6.8% and 10.2%. AF in patients with cirrhosis is associated with adverse outcomes in both pre‐transplant and post‐transplant settings, including an increased risk of stroke when compared to the general population. We review the pathogenesis of AF in general and in cirrhosis. This review also provides guidance on the management of AF, including the use of anticoagulation and rate versus rhythm control. In the absence of strict contraindications, all patients with cirrhosis and AF should be anticoagulated. The use of DOACs is preferred over vitamin K antagonists. In patients with a high bleeding risk, a DOAC with an approved antidote may be preferred. Conclusions: Atrial fibrillation is increased in patients with cirrhosis. AF management requires careful consideration of treatment options. Since patients with cirrhosis were excluded from all major randomised clinical trials, dedicated research on the pathophysiology and management of AF in cirrhosis is needed. [ABSTRACT FROM AUTHOR]

Background: In cirrhosis, cardiac systolic dysfunction as part of cirrhotic cardiomyopathy affects prognosis. Myocardial mechano‐energetic efficiency (MEE) is an estimate of left ventricular performance. In this study we investigated the relation of MEE to patient characteristics and its impact on survival in patients with cirrhosis. Patients and Methods: We included 283 patients with cirrhosis of different severity according to the Child−Pugh classifications (A/B/C: 106/87/90). All patients had a liver vein catheterization and a hemodynamic investigation performed including determination of cardiac output (CO), stroke volume and heart rate (HR). These data were used to assess MEE, which was defined as (stroke volume/HR) × 1.666. Results: Eighty‐nine percent of patients had portal hypertension (hepatic venous pressure gradient >5 mmHg) and 80% indications of hyperdynamic circulatory state (increased CO and HR). There was no difference in MEE in Child−Pugh class C patients (2.03) versus Child−Pugh class A (1.98) and B (2.05) patients. In Child−Pugh class C patients, low MEE was associated with a poorer prognosis. Conclusion: In our study, MEE does not seem to be associated with severity of the liver disease, but in patients with advanced disease low MEE is associated with a poorer prognosis. The prognostic impact of MEE should be further investigated. [ABSTRACT FROM AUTHOR]

Objective: To identify patients with occult cardiac dysfunction and its relationship with the severity of liver impairment. Method: This is a Judgment (Purposive) Sampling, cross-sectional study that was conducted at Kafrelsheikh University Hospital, Egypt, from November 2019 to December 2020, and comprised adult patients of either gender with liver cirrhosis. After detailed history, a clinical examination, pathological assessment and cardiac evaluation based on electrocardiogram and echocardiography, the patients were divided into three groups. Patients who had dyspnoea or cyanosis were in group A, those who did not have dyspnoea or cyanosis but had electrocardiogram and echocardiography abnormalities were in group B, and patients who did not have dyspnoea, cyanosis or electrocardiogram and echocardiography abnormalities were in group C. The severity of the liver disease was evaluated using Child-Pugh and Model of End Liver Disease scores. Data was analysed using SPSS 20. Results: Of the 300 patients, 153(51%) were males and 147(49%) were females. The overall mean age was 55.1±5.1 years (range: 20-60 years). There were 58(19.33%) patients in group A, 108(36%) in group B and 134(44.66%) in group C. Group A patients showed higher Child-Pugh and Model of End Liver Disease scores than the other groups (p6 and Model of End Liver Disease score >37 yielded the best accuracy for detecting cardiac abnormalities in group B (p

Abstract Background Without 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. Results Diastolic 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. Conclusion Most 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.

BackgroundDiastolic dysfunction (DD), one of the earliest signs of cirrhotic cardiomyopathy (CCM), is included in the revised 2019 CCM criteria. Nonetheless, relevant research regarding the effects of revised DD on post-liver transplantation (LT) outcomes remains limited.MethodsThis retrospective study enrolled patients who underwent LT for decompensated cirrhosis, from January 2018 to March 2021. Patients were divided into DD and non-DD groups. Clinical data were collected. Patients were followed up with, for at least 1 year post-LT; cardiovascular adverse events (AEs) and survival status were recorded. Risk factors were identified using 1:2 propensity score matching (PSM), after adjusting for confounding factors. The caliper value was set to 0.02.ResultsOf 231 patients, 153 were diagnosed with DD (male, 81.8%; mean age, 51.5 ± 9.5 years). Nineteen patients with DD died within 1 year, post-LT. After PSM, 97 and 60 patients were diagnosed with and without DD, respectively. Patients with DD had longer intensive care unit (ICU) stays, higher perioperative cardiovascular AEs, and higher mortality rates than those without DD. In a multivariate analysis, interventricular septum (IVS), left atrial volume index (LAVI), and potassium levels were independent prognostic factors of perioperative cardiovascular AEs, while a decreased early diastolic mitral annular tissue velocity (e’), increased neutrophil-to-lymphocyte ratio (NLR) and tumor markers were predictors of mortality within 1 year post-LT after PSM (P

Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed.

Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy.

OBJECTIVE: To determine the frequency of cardiomyopathy and its manifestations in patients with liver cirrhosis presenting at Tertiary Care Hospital, Karachi. METHODOLOGY: This cross-sectional study was carried out in Medical unit I of Jinnah Postgraduate Medical Center, Karachi, from July-December 2017. The sampling technique employed was nonprobability consecutive samplings. 95 patients with liver cirrhosis diagnosed earlier on clinical and investigations were included. Systolic dysfunction of the heart on Echocardiography was considered at EF0.44 was in 47.4% cases and heart rate >100 was in 33.7% cases. The proBNP >93 pg/ml was observed in 77.4% male patients and >144 pg/ml in 87.5% female patients. Cirrhotic cardiomyopathy was observed in 69.5% of patients and was not significantly associated with gender, age, duration of disease, and child Pugh class. CONCLUSION: Although there is a considerably high frequency of cardiomyopathy in cirrhotic patients, its presence, generally, is not realized and, thus, due attention is not given. Highlighting its high frequency, its need for workup and treatment may improve the quality of life of these patients.

The curative therapy for patients with end-stage liver disease is liver transplantation. However, liver transplantation challenges the cardiovascular system, and is associated with major adverse cardiovascular events (MACE). Immediately after implantation of the liver graft, changes in cardiac preload and afterload increase the cardiac workload. Longer-term postoperatively, a more sedentary lifestyle and enhanced appetite increase obesity and body mass index. Immunosuppressants may also affect the cardiovascular system. All these factors that liver recipients encounter impact the function of the cardiovascular system. Cardiac events are the third-leading cause of death in liver recipients. This review describes the pertinent factors that predispose to development of MACE after liver transplantation, and how to predict these cardiovascular events in the post-transplant period. We review the roles of metabolic syndrome, renal dysfunction, non-alcoholic fatty liver disease, diagnostic tests such as imaging and biomarkers, and parameters such as systolic and diastolic dysfunction, and QT interval prolongation in cardiovascular events. We summarize the current literature on scoring systems to predict cardiovascular events. [ABSTRACT FROM AUTHOR]

The prognostic role of cardiac dysfunction in cirrhotic patients is increasingly recognized. We studied its impact on morbidity and mortality before and after liver transplantation (LT) including development of post‐transplant cardiovascular disease (CVD). In this retrospective study, cirrhotic patients who underwent LT assessment from January 2010 to December 2020 were reviewed. Demographics, cardiac investigations and clinical courses were analyzed to identify the prevalence of cardiac dysfunction and its role in LT outcomes. Survival analysis was performed using Cox proportional hazard regression modelling, with LT as a time‐varying covariate and as an interaction variable with cardiac dysfunction. Three hundred and eight patients (70% male) were studied. The median (interquartile range) age at LT assessment was 56 (12) years. Cardiac dysfunction was found in 178 (58%) patients (diastolic, 169; systolic, 26; both, 17) and was significantly associated with hepatorenal syndrome/acute kidney injury and peri‐ and post‐transplant morbidity (adjusted odds ratio [aOR] 1.94, 95% CI 1.06–3.52, P <.001; aOR 2.01, 95% CI 1.06–3.82, P =.033; aOR 1.9, 95% CI 1.01–3.65, P =.023, respectively). Cardiac dysfunction was not associated with mortality before (adjusted hazard ratio [aHR] 1.01, 95% CI.99–1.01) or after LT (aHR.74, 95% CI.4–1.05. Post‐transplant CVD (61% cardiac failure) occurred in 36 patients, and there was no significant association with cardiac dysfunction (P =.11). Cardiac dysfunction was common in LT candidates and was significantly associated with morbidity before and after LT. Studies on the role of advanced echocardiographic parameters to improve diagnosis of cardiac dysfunction and optimize LT outcomes are needed. [ABSTRACT FROM AUTHOR]