Relationship between Heart Disease and Liver Disease: A Two-Way Street

In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation

Pathophysiological and clinical approach to cirrhotic cardiomyopathy.

Hyperdynamic circulation, systolic and diastolic left ventricular dysfunction and certain electrophysiological abnormalities have been associated with cirrhosis and known for a long time. These clinical features have been introduced as cirrhotic cardiomyopathy (CCM), which is characterized by blunted myocardial contractile responsiveness to physical, physiological and pharmacological stress. Importantly, cardiac dysfunction can be reversible and can improve due to effective medical treatment and also after liver transplantation. Echocardiography and electrocardiography are essential tools for recognizing the characteristic changes in the myocardial function and also the alterations in the electrophysiological properties of the heart. Laboratory markers are auxiliary modalities further aiding the establishment of the correct diagnosis. In this review, we aimed to collect the pathophysiological background and clinical characteristics of CCM with the intention of summarizing the current possibilities for the diagnosis establishment and treatment of this cardio-hepatic disorder. Key words: liver cirrhosis – cardiomyopathy – heart failure – arrhythmias. Abbreviations : A: late diastolic transmitral peak flow velocity; ACE: angiotensin converting enzyme; ANP: atrial natriuretic peptide; ARB: angiotensin receptor blocker; BNP: brain natriuretic peptide; cAMP: cyclic adenosine monophosphate; CCM: cirrhotic cardiomyopathy; CGRP: calcitonin gene-related peptide; CO: carbon monoxide; DD: diastolic dysfunction; DT: deceleration time; E: early diastolic transmitral peak flow velocity; Ea: early diastolic velocity of the septal mitral annulus; EF: ejection fraction; MUGA: Multi Gated Acquisition Scan; NO: nitric oxide; NSBB: non-selective beta-blocker; pro-BNP: pro-brain natriuretic peptide; QTc: corrected QT interval; RAAS: renin-angiotensin aldosterone system; RALES: Randomized Aldactone Evaluation Study; suPAR: urokinase-type plasminogen activator receptor; TDI: Tissue Doppler Imaging; TIPS: transjugular intrahepatic portosystemic shunt; TNF-alpha: tumor necrosis factor-alpha

Nonischemic Cardiomyopathy in Liver Transplant Recipients

Nonischemic cardiomyopathy is a collective term, encompassing a spectrum of cardiac comorbidities, accompanying the progressing end-stage liver disease. Alcoholic and cirrhotic cardiomyopathies are the most researched, well-known clinical entities in the list of nonischemic cardiac disorders that bear the most substantial impact on the clinical course, management, and outcomes of liver transplantation in ESLD patients. In this chapter, morphology, pathophysiology, diagnostic criteria, clinical manifestations, and management options of nonischemic cardiomyopathy in liver transplant candidates and recipients, the patients with end-stage liver disease due to advanced stages of cirrhosis, are discussed

Right Heart Remodeling in Patients with End-Stage Alcoholic Liver Cirrhosis: Speckle Tracking Point of View

BACKGROUND: Data regarding cardiac remodeling in patients with alcoholic liver cirrhosis are scarce. We sought to investigate right atrial (RA) and right ventricular (RV) structure, function, and mechanics in patients with alcoholic liver cirrhosis. METHODS: This retrospective cross-sectional investigation included 67 end-stage cirrhotic patients, who were referred for evaluation for liver transplantation and 36 healthy controls. All participants underwent echocardiographic examination including strain analysis, which was performed offline. RESULTS: RV basal diameter and RV thickness were significantly higher in patients with cirrhosis. Conventional parameters of the RV systolic function were similar between the observed groups. Global, endocardial, and epicardial RV longitudinal strains were significantly lower in patients with cirrhosis. Active RA function was significantly higher in cirrhotic patients than in controls. The RA reservoir and conduit strains were significantly lower in cirrhotic patients, while there was no difference in the RA contractile strain. Early diastolic and systolic RA strain rates were significantly lower in cirrhotic patients than in controls, whereas there was no difference in the RA late diastolic strain rate between the two groups. Transaminases and bilirubin correlated negatively with RV global longitudinal strain and RV-free wall strain in patients with end-stage liver cirrhosis. The Model for End-stage Liver Disease (MELD) score, predictor of 3-month mortality, correlated with parameters of RV structure and systolic function, and RA active function in patients with end-stage liver cirrhosis. CONCLUSIONS: RA and RV remodeling is present in patients with end-stage liver cirrhosis even though RV systolic function is preserved. Liver enzymes, bilirubin, and the MELD score correlated with RV and RA remodeling

LIVER STIFFNESS EVALUATION USING ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY IN PEDIATRIC AND ADULT PATIENTS WITH CONGENITAL HEART DISEASE

Background: Hepatic complications are common in patients with congenital heart disease as a consequence of the primary cardiac defect or as a result of surgical palliation (e.g. Fontan procedure). Liver involvement represents a significant challenge and an adequate hepatic surveillance is fundamental. Liver biopsy represents the gold standard for diagnosis and staging of hepatic fibrosis but it’s an invasive procedure not suitable for a routine setting. Acoustic radiation force impulse (ARFI) elastography is a recently developed technique that allows to assess hepatic stiffness in a non-invasive and reproducible way. The usefulness of ARFI imaging has been described in adult Fontan patients but only few studies have been reported in the pediatric Fontan population and no one in CHD others than Fontan. Aim: The aims of this study were to assess liver stiffness, using ElastPQTM acoustic radiation force impulse elastography, in pediatric and adult patients with CHD, to compare liver stiffness values with healthy controls and to analyze possible associations between ARFI values and clinical, biochemical, cardiac and hepatic parameters. Materials and methods: Pediatric and adult patients that underwent heart surgery for CHD and were followed at the Cardiology Unit of the “Azienda Ospedaliera Universitaria Integrata” of Verona between October 2018 and October 2020 were prospectively enrolled. Controls subjects without any liver or cardiac disease matched for age and sex to the case group were also included. The latest laboratory tests and echocardiogram available were collected. Liver ultrasound and ARFI measurement of liver stiffness were performed by a specifically trained single expert radiologist using the Philips Healtcare® ultrasound with ElastPQTM software. Results: A total of 50 subjects were enrolled for the study: 20 Fontan patients (13 males, median age at ARFI 8.4 years), 13 non-Fontan (9 males, median age at ARFI 4.8 years) and 17 controls (6 males, median age at ARFI 10 years). The median values of ARFI elastography were significantly higher in patients with CHDs (Fontan and non-Fontan patients) compared to control subjects (p<0.01). Patients with morphological right ventricle overload showed significantly higher results (p=0.02). The cut-off of 5.7 kPa at elastography was used to discriminate between normal liver and liver with signs of congestion or fibrosis. All controls subjects showed ARFI values <5.7 kPa whereas only 25% of Fontan patients and 46% of non-Fontan were below that threshold. Liver stiffness values were positively correlated with time from surgery and age at liver evaluation (p<0.01). The number of platelets and white blood cells were inversely related to liver stiffness measurements (p=0.04 and p=0.05 respectively). The AST to platelet ratio index positively correlated with ARFI elastography results (p<0.03). No significant correlations between ARFI results and other biochemical or cardiac parameters were found. Conclusions: Our data showed that the median values of liver stiffness measured with ElastPQTM pSWE were significantly higher in patients with CHDs compared to control subjects and, in particular, in those with morphological right ventricle overload. Liver stiffness values were also correlated with time from surgery and age at liver evaluation. The number of platelets and white blood cells were inversely related to liver stiffness measurements supporting the need of a screening for portal hypertension and splenomegaly in these patients. The AST to platelet ratio index was also correlated to ARFI elastography results suggesting that liver stiffness may reflect the evolution of liver fibrosis. In conclusion, our study demonstrated, for the first time in literature, that acoustic radiation force impulse elastography (pSWE) with ElastPQTM software can be a useful tool to assess liver stiffness in patients with Fontan circulation and other congenital heart disease

The End-Organ Impairment in Liver Cirrhosis: Appointments for Critical Care

Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs

Management of Cardiopulmonary Complications of Cirrhosis

Advanced portal hypertension accompanying end-stage liver disease results in an altered milieu due to inadequate detoxification of blood from splanchnic circulation by the failing liver. The portosystemic shunts with hepatic dysfunction result in an increased absorption and impaired neutralisation of the gastrointestinal bacteria and endotoxins leads to altered homeostasis with multiorgan dysfunction. The important cardiopulmonary complications are cirrhotic cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension, and right-sided hydrothorax

Cirrhotic cardiomyopathy

Cirrhotic cardiomyopathy is the term used to describe a constellation of features indicative of abnormal heart structure and function in patients with cirrhosis. These include systolic and diastolic dysfunction, electrophysiological changes, and macroscopic and microscopic structural changes. The prevalence of cirrhotic cardiomyopathy remains unknown at present, mostly because the disease is generally latent and shows itself when the patient is subjected to stress such as exercise, drugs, hemorrhage and surgery. The main clinical features of cirrhotic cardiomyopathy include baseline increased cardiac output, attenuated systolic contraction or diastolic relaxation in response to physiologic, pharmacologic and surgical stress, and electrical conductance abnormalities (prolonged QT interval). In the majority of cases, diastolic dysfunction precedes systolic dysfunction, which tends to manifest only under conditions of stress. Generally, cirrhotic cardiomyopathy with overt severe heart failure is rare. Major stresses on the cardiovascular system such as liver transplantation, infections and insertion of transjugular intrahepatic portosystemic stent-shunts (TIPS) can unmask the presence of cirrhotic cardiomyopathy and thereby convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome. Pathogenic mechanisms of cirrhotic cardiomyopathy are multiple and include abnormal membrane biophysical characteristics, impaired β-adrenergic receptor signal transduction and increased activity of negative-inotropic pathways mediated by cGMP. Diagnosis and differential diagnosis require a careful assessment of patient history probing for excessive alcohol, physical examination for signs of hypertension such as retinal vascular changes, and appropriate diagnostic tests such as exercise stress electrocardiography, nuclear heart scans and coronary angiography. Current management recommendations include empirical, nonspecific and mainly supportive measures. The exact prognosis remains unclear. The extent of cirrhotic cardiomyopathy generally correlates to the degree of liver insufficiency. Reversibility is possible (either pharmacological or after liver transplantation), but further studies are needed

CIRRHOTIC CARDIOMYOPATHY IN EGYPTIAN PATIENTS

Background: Liver  cirrhosis is   a health care problem in  Egypt  caused  by the high prevalence of  hepatitis C virus (HCV)  infection that affects 15-20 % of the population  . Cirrhotic cardiomyopathy is the term used to describe a constellation of features indicative of abnormal heart structure and function in patients with cirrhosis. Aim of this study is to assess the pattern and the extent of cardiac affection in cirrhotic patients and its relation to the presence or absence of ascites. Materials  and methods: This study was carried out on 70 patients with liver cirrhosis and 30 healthy controls. All persons were subjected to careful history & physical examination, laboratory investigations, abdominal ultrasonography ,and echocardiography. Results:   left ventricle end diastolic diameter was significantly  increased in cirrhotic patients with  ascites (5.40±0.58)  and without ascites ((5.31±0.51), compared to the control group (4.52±0.58) (p<0.05), . left ventricle end systolic diameter was      increased in cirrhotic patients with  ascites (3.57±2.2)  and without ascites (3.46±3.1), without ascites (3.18±2.5)but the difference was statistically non significant    (p > 0.05).   Left atrium diameter & Right ventricular end diastolic diameter were significantly increased in cirrhotic patients compared to the control group (p<0.05  The  pulmonary artery pressure  was elevated in cirrhotic patients compared to the control group .. Conclusion:  In the present study ptient with Liver cirrhosis were  associated with significant enlargement of cardiac chambers and diastolic dysfunction compared to the control group specially   in  the presence of ascites.Â