Diagnosis Of Cirrhotic Cardiomyopathy Research Articles

Cirrhotic cardiomyopathy – Clinically fact or academic curiosity? Review. Part 2: ECG, functional tests, images, biomarkers, screening for coronary heart disease and differentianting diagnosis

The diagnosis of Cirrhotic Cardiomyopathy is based on severe hepatic cirrosis with deterioration of cardiac function without previous cardiopathy, but this is subclinical during a long time. In this second part we review the non-invasive diagnostic methods and their prognostic value in patients with or without hepatic transplant, from ECG to cardiac images of magnetic resonance.

Update on cirrhotic cardiomyopathy: from etiopathogenesis to treatment.

Cirrhotic cardiomyopathy represents a syndrome of cardiac dysfunction associated with advanced liver disease. It is the result of complex pathophysiological processes that complicate the course of the disease, and is generally associated with a poor prognosis. Pathophysiologically, portal hypertension is the key factor leading to hyperdynamic circulation, via over-activation of the neurohumoral axis. Intestinal obstruction, subclinical inflammation and hepatocellular insufficiency, with defective synthesis or metabolism of several vasoactive mediators, are essential components of this process. Since it is usually unapparent at rest and only unmasked by an inadequate cardiac response to hemodynamic stress, the diagnosis of cirrhotic cardiomyopathy is challenging and demands a multimodal approach. There is currently no specific therapy, but there are prognostically effective drugs available to treat heart failure. Therefore, it is crucial to identify patients with chronic liver disease and heart failure in order to ameliorate their outcome. This article attempts to highlight the most important aspects of cirrhotic cardiomyopathy and draws attention to this condition.

The Contemporary Role of Speckle Tracking Echocardiography in Cirrhotic Cardiomyopathy.

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 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.

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.

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.

Left ventricular function is related with amphiregulin and fibrosis markers in cirrhotic cardiomyopathy.

The relationship between left ventricle (LV), extracellular matrix remodeling and fibrosis-linked amphiregulin (ARG) in cirrhotic cardiomyopathy (CCM) is unknown. The aim of the study was to investigate the associations between markers of extracellular matrix remodeling and ARG in cirrhosis and their association with indicators of ventricular remodeling and LV functional parameters. In hepatitis C virus (HCV) patients with cirrhosis, who underwent echocardiography, the presence of left ventricular diastolic dysfunction (LVDD) was determined by having gradable diastolic dysfunction in accordance with modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. A total of 87 cirrhotic patients were consecutively analyzed. Based on detailed echocardiographic assessment - 35 HCV patients with cirrhosis had normal left ventricular diastolic function (non-CCM group), whereas 52 patients had LVDD (CCM group). ARG was measured by enzyme-linked immunosorbent assay. The ARG levels were significantly increased in the CCM group compared to the non-CCM group (P<0.001). ARG levels in all HCV patients were independently associated to the presence of CCM, and showed significant correlations with LVDD. The close relationship between ARG levels and the direct serum marker of fibrosis, and selected markers of extracellular matrix (i.e. transforming growth factor-beta1 (TGF-β1), and carboxyterminal propeptide of type I collagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), tissue inhibitor of matrix proteinase-1 (TIMP-1), respectively), ventricular remodeling (i.e. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-T (hs-TnT)), and LV functional parameters suggest an active role in the myocardial injury. Using ROC analysis, the best marker for the diagnosis of CCM was NT-proBNP with AUROC = 0.796. The area under the curve of ARG (AUROC = 0.709) for predicting CCM was greater than this for PICP (AUROC = 0.662) and similar to this hs-TnT (AUROC = 0.753). The simultaneous monitoring of serum ARG and markers of extracellular matrix and ventricular remodeling can be helpful for the alterations in myocardial function control in HCV patients with cirrhosis.

What’s New in Cirrhotic Cardiomyopathy?—Review Article

Cirrhotic cardiomyopathy (CCM) is a relatively new medical term. The constant development of novel diagnostic and clinical tools continuously delivers new data and findings about this broad disorder. The purpose of this review is to summarize current facts about CCM, identify gaps of knowledge, and indicate the direction in which to prepare an updated definition of CCM. We performed a review of the literature using scientific data sources with an emphasis on the latest findings. CCM is a clinical manifestation of disorders in the circulatory system in the course of portal hypertension. It is characterized by impaired left ventricular systolic and diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. However, signs and symptoms reported by patients are non-specific and include reduced exercise tolerance, fatigue, peripheral oedema, and ascites. The disease usually remains asymptomatic with almost normal heart function, unless patients are exposed to stress or exertion. Unfortunately, due to the subclinical course, CCM is rarely recognized. Orthotopic liver transplantation (OLTx) seems to improve circulatory function although there is no consensus about its positive effect, with reported cases of heart failure onset after transplantation. Researchers indicate a careful pre-, peri-, and post-transplant cardiac assessment as a crucial point in detecting CCM and improving patients’ prognosis. There is also an urgent need to update the CCM definition and establish a diagnostic algorithm for early diagnosis of CCM as well as a specific treatment of this condition.

Cirrhotic cardiomyopathy

A cirrhotic cardiomyopathy (CCM) can be observed in patients with end-stage liver disease and is characterized by a systolic and/or diastolic dysfunction in the absence of pre-existing heart diseases. While the cardiac dysfunction is often masked at rest, it typically manifests itself during cardiovascular challenges such as hypovolemia, physical stress, or sepsis. The diagnosis of CCM is challenging and predominantly based on echocardiographic measurements to identify subclinical cardiac dysfunction. Additional diagnostic criteria include electrophysiological abnormalities such as QT-interval prolongation, an abnormal chronotropic or inotropic response to stress, elevated cardiac biomarkers such as natriuretic peptides, and structural cardiac abnormalities like left atrium enlargement. There is no specific therapy for CCM. Supportive measures and regular cardiac evaluation of high-risk patients and transplant candidates are important to reduce the risks associated with invasive procedures and treatments.

Cirrhotic Cardiomyopathy-A Veiled Threat.

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction in patients with liver cirrhosis without preexisting cardiac disease. According to the definition established by the World Congress of Gasteroenterology in 2005, the diagnosis of CCM includes criteria reflecting systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances. Because of minimal or even absent clinical symptoms and echocardiographic signs at rest according to the 2005 criteria, CCM diagnosis is often missed or delayed in most clinically stable cirrhotic patients. However, cardiac dysfunction progresses in time and contributes to the pathogenesis of hepatorenal syndrome and increased morbidity and mortality after liver transplantation, surgery, or other invasive procedures in cirrhotic patients. Therefore, a comprehensive cardiovascular assessment using newer techniques for echocardiographic evaluation of systolic and diastolic function, allowing the diagnosis of CCM in the early stage of subclinical cardiovascular dysfunction, should be included in the screening process of liver transplant candidates and patients with cirrhosis in general. The present review aims to summarize the most important pathophysiological aspects of CCM, the usefulness of contemporary cardiovascular imaging techniques and parameters in the diagnosis of CCM, the current therapeutic options, and the importance of early diagnosis of cardiovascular impairment in cirrhotic patients.

Redefining Cirrhotic Cardiomyopathy for the Modern Era.

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end-stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice-based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Survival at 2years among liver cirrhotic patients is influenced by left atrial volume and left ventricular mass.

Cirrhotic cardiomyopathy (CC) may interact with the clinical course of cirrhosis and can be implicated in the development of several complications in advanced liver disease. The best and easiest parameters which should define a condition of reduced cardiac reserve in cirrhosis are still controversial. This study was aimed at selecting the cardiac parameters, derived by Doppler echocardiography, predictive of survival during follow-up. This study included cirrhotic patients without cardiovascular or pulmonary diseases. Patients were studied in stable conditions. Doppler echocardiography was used to select parameters associated with survival. Among the others, left atrial volume (LAVi) and left ventricular mass indexed to body surface area (LVMi) were evaluated. A comparison was performed with the parameters presently applied for the definition of CC according to the Montreal criteria. Ninety cirrhotic patients have been included (males 66%, alcohol origin 31%, post-viral 54%, Child-Pugh A 53%, B 29% and C 18%). Patients were followed up for at least 24months. Twenty-six patients had a diagnosis of CC according to the Montreal criteria. During follow-up, 24 patients died. Overall mortality was 26.7%. Patients presenting higher LAVi and lower LVMi were those at higher risk to die (P=.04 and P=.007 respectively). No difference in survival was seen in patients with a diagnosis of CC. An increased LAVi and a decreased LVMi were able to differentiate among patients with a lower survival at 2years. These parameters need to be considered for prognostic evaluation in cirrhotics.

The early stage of cirrhotic cardiomyopathy is a risk factor for postreperfusion syndrome during liver transplantation? A retrospective observational study

Objectives: Despite normal or high cardiac output at rest, cirrhotic patients often exhibit abnormal cardiac function when subjected to stress. During the pretransplant cardiac workup, the diagnosis of cirrhotic cardiomyopathy would be easily missed without the aid of some supportive criteria because most patients have normal rest echocardiography. The period of highest hemodynamic instability during liver transplantation occurs after revascularization of the liver graft and is called postreperfusion syndrome. The aim of this study was to investigate if patients at risk for cirrhotic cardiomyopathy have a higher risk for postreperfusion syndrome during liver transplantation. The secondary purpose of the study was to assess if the supportive criteria used for cirrhotic cardiomyopathy evaluation correlate with the severity of the liver disease. Material and Methods: The study group included 52 patients undergoing orthotopic liver transplantation for cirrhosis. The variables recorded were: demographic data, MELD and MELD Na scores, the length of the QT interval corrected for heart rate, plasma levels of brain natriuretic peptide (BNP), cold and warm ischemia times, vasopressor use, transfusional requirements and the occurrence of postreperfusion syndrome during transplantation. Results: The patients were divided into 2 subgroups based on the occurrence of the postreperfusion syndrome. There was no statistically significant difference in BNP levels, length of QTc interval, MELD or MELD Na scores between the subgroups. BNP levels were correlated with QTc interval length (p=0.005), MELD and MELD Na scores (p=0.025 and p=0.001). The correlation between QTc interval length and the severity scores was not statistically significant. Conclusions: Our study showed that postreperfusion syndrome was not correlated with the severity of the liver disease or with the presence of risk factors indicating cirrhotic cardiomyopathy. From the supportive criteria studied, only BNP levels correlate with the severity of the liver disease.

Prevalence and impact on survival of hepatopulmonary syndrome and cirrhotic cardiomyopathy in a cohort of cirrhotic patients

Extrahepatic complications of cirrhosis increase the risk for decompensation of the liver disease and death. Previous studies show common pathogenetic mechanisms involved in the development of hepatopulmonary syndrome and cirrhotic cardiomyopathy. We aimed to assess the link between these entities and their effect on disease-related patient morbidity and mortality. Seventy-four consecutive cirrhotic patients without prior history of cardiovascular and pulmonary disease were included in a prospective observational study. Routine blood work, arterial blood gas analysis, pulse oximetry measurements, N-terminal pro-brain natriuretic peptide levels and contrast enhanced echocardiography examination with tissue Doppler imaging were performed in all patients. Patients were followed up for a median of 6 months and disease-related adverse events and death were the main outcomes tested. Statistical analysis was conducted according to the presence of hepatopulmonary syndrome or cirrhotic cardiomyopathy. Hepatopulmonary syndrome was diagnosed in 17 patients (23%) and cirrhotic cardiomyopathy in 30 patients (40.5%). There was no association between the presence of cirrhotic cardiomyopathy and the existence of mild or moderate hepatopulmonary syndrome. No echocardiographic parameters were useful in predicting the presence of hepatopulmonary syndrome. N-terminal pro-brain natriuretic peptide levels and length of QT interval did not aid in diagnosis of cirrhotic cardiomyopathy. Neither entity had significant influence on disease-related outcomes in the follow-up period. Hepatopulmonary syndrome and cirrhotic cardiomyopathy are independent complications arising in cirrhosis and have a limited influence on morbidity and mortality on a pre-liver transplantation population.

Echocardiography in Chronic Liver Disease: Systematic Review

Doppler echocardiography (Echo) is a non-invasive method of excellent accuracy to screen portopulmonary hypertension (PPH) and to assess intrapulmonary shunts (IPS) in chronic liver disease (CLD). In the past decade, Echo proved to play a fundamental role in the diagnosis of cirrhotic cardiomyopathy (CCM). To perform a systematic review of relevant articles on the subject 'Echo in CLD'. In November 2011, a systematic review was performed in the PubMed, LILACS and SciELO databases, and the characteristics of the studies selected were reported. The search based on descriptors and free terms obtained 204 articles (179 in Pubmed, 21 in LILACS, and 1 in SciELO). Of those 204 articles, 22 were selected for systematic review. A meta-analysis could not be performed because of the heterogeneity of the articles. Echo should be part of CLD stratification for screening PPH, IPS and CCM, because, most of the time, such complications are diagnosed only when patients are already waiting for a liver transplant.