Evidence of Ventricular Arrhythmogenicity and Cardiac Sympathetic Hyperinnervation in Early Cirrhotic Cardiomyopathy

Cirrhotic cardiomyopathy (CMP) is associated with altered cardiac electrophysiological (EP) properties, which leads to the risk of ventricular arrhythmias (VAs). We aimed to evaluate the EP properties, autonomic, and structural remodeling in a rabbit model with early liver cirrhosis (LC). Twelve rabbits were assigned to the sham and LC groups. The early-stage LC was induced by the ligation of the common bile duct. All rabbits received an EP study, VA inducibility test, myocardial, and liver histology staining. Western blot analyses of protein expression and tyrosine hydroxylase stain for sympathetic nerves were performed. The effective refractory period the LC group was significantly longer than the sham group [i.e., left ventricle (LV) 205.56 ± 40.30 vs. 131.36 ± 7.94 ms; right ventricle (RV) 206.78 ± 33.07 vs. 136.79 ± 15.15 ms; left atrium (LA) 140.56 ± 28.75 vs. 67.71 ± 14.29 ms; and right atrium (RA) 133.78 ± 40.58 vs. 65.43 ± 19.49 ms, all p < 0.01], respectively. The VA inducibility was elevated in the LC group when compared with the sham group (i.e., 21.53 ± 7.71 vs. 7.76 ± 2.44%, p = 0.013). Sympathetic innervation (102/μm2/mm2) was increased in all cardiac chambers of the LC group compared with the sham group (i.e., LV 9.11 ± 4.86 vs. 0.17 ± 0.15, p < 0.01; RV 4.36 ± 4.95 vs. 0.18 ± 0.12, p = 0.026; LA 6.79 ± 1.02 vs. 0.44 ± 0.20, p = 0.018; and RA 15.18 ± 5.12 vs. 0.10 ± 0.07, p = 0.014), respectively. Early LC is presented with an increased ventricular vulnerability, structural heterogeneity, and sympathetic innervation. Close monitoring for fatal arrhythmias is warranted in patients with early stages of LC.

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.

Peptidylglycine α-Amidating Monooxygenase And Adrenomedullin Measurement In Cirrhosis Suggesting Cardiomyopathy

Peptidylglycine α-amidating monooxygenase (PAM) is a processing enzyme involved in maturation of regulatory peptides. One product of PAM activity is adrenomedullin (bio-ADM), which regulates vascular tone and endothelial integrity. In this study, we examined PAM activity and bio-ADM concentrations in patients with various degrees of hepatic cirrhosis including the role of the liver in net release of the two markers. We enrolled 48 patients with cirrhosis and 16 control subjects: The patients were evenly distributed according to the Child-Turcotte classification. PAM activity was progressively increased in cirrhotic patients but without a net release across the liver, leg, or kidney. In contrast, bio-ADM concentrations were not only associated to severity of disease but also found to be directly released by the liver. Given the major expression of PAM in the heart, we propose that increased PAM activity in plasma from patients with cirrhosis may reflect cardiac involvement, e.g. cirrhotic cardiomyopathy.

A STUDY OF ECHOCARDIOGRAPHIC CHANGES IN PATIENTS WITH CIRRHOSIS OF LIVER

Background/Aims: Cirrhosis is associated with a significant number of cardiac abnormalities but, the information available is scanty about the changes associated with it in India. Which include increased cardiac output, increased wall thickness of cardiac chambers, left ventricular diastolic dysfunction, and PAH. These cardiac abnormalities in patients with Cirrhosis have been termed as Cirrhotic Cardiomyopathy. Cirrhotic Cardiomyopathy may be a significant cause of morbidity and mortality in patients with Cirrhosis. With the advent of increased liver transplantation in India, this entity may have an impact on transplantation success. The present study aims to evaluate the cardiac abnormalities in patients with cirrhosis using 2D Echocardiography to detect the occurrence of LV dysfunction, pulmonary hypertension, pericardial effusion, and to assess the contribution of cardiac dysfunction on mortality, if any. Methodology: Thirty patients with Cirrhosis (alcoholic and non-alcoholic) were enrolled. Thirty age and sex-matched controls without cardiovascular disease were included for comparison. Data collection was done by clinical history taking, examination, and investigations. All subjects underwent Echo study was at 0, 6 and12 months and controls at the start of the study. Observations and Results: 1. The mean age of study group was 54.5 ± 15 yrs among them, males constituted 93 % of the study population, the majority of patients were in Child class B (43.3%), and Child A (40%). None of the study population died during follow up. 2. The salient Echocardiographic abnormalities noted in the study population were a) Interventricular septal thickness showed significant change compared to control (9.80 ± 1.06 vs. 8.00 ± 1.00mm mm). b) Doppler echocardiography detected elevated pulmonary arterial pressure (PAP) in the study population compared to control (20.73 ±2.43mm Hg vs.18.26 ± 2.1mm Hg). c) Diastolic dysfunction occurred in the form of increased Deceleration time (223.17 ± 13.93 ms vs. 190.83 ± 14.0ms) and increased E: A ratio (1.10±0.1 vs. 1.04±0.12) was noted in subjects with Cirrhosis. Two of the study subjects had pericardial effusion. (6.7%) 3. There is no evidence of systolic dysfunction noted in the study population. 4. There is no correlation between the severity of Cirrhosis and echocardiographic changes. 5. There were no differences in echo parameters among patients with alcoholic or non-alcoholic etiology of Cirrhosis. 6. There was no fatality recorded due to cardiac dysfunction Conclusion: 1. This study demonstrates that Indian patients with cirrhosis do have diastolic dysfunction. In the absence of other cardiac disease risk factors, this dysfunction can be attributed only to cirrhotic cardiomyopathy. 2. Echocardiography plays a significant role in detecting early cardiac changes in cirrhosis however, these changes do not seem to be a predictor of increased mortality in cirrhosis patients.

Cardiomyopathy in Cirrhotic Patients and Its Relationship with the Severity of Cirrhosis

Study Objectives: To determine the frequency of cirrhotic cardiomyopathy in patients with liver cirrhosis and to compare it across varying grades of cirrhosis on Child Turcotte Pugh classification. Study Design and Settings: It was a descriptive cross-sectional study carried at Department of Medicine, Lahore General Hospital Lahore over 1 year from Jan 2018 to Dec 2018. Patients and Methods: The present research involved 100 male and female patients aged between 16-70 years having liver cirrhosis diagnosed at least 6 months ago. These patients underwent echocardiographic screening of cardiomyopathy which was diagnosed by the presence of diastolic dysfunction (i.e. increased E/A ratio>1). An informed written consent was obtained from every patient. Results of the Study: There was a male predominance (M:F, 1.6:1) among cirrhotic patients with a mean age of 51.9±9.8 years. The mean BMI was 26.5±3.7 Kg/m2 while the mean duration of cirrhosis was 22.0±10.9 months. Majority (49.0%) of the patients belonged to CTP Class C followed by Class-B (39.0%) and Class-A (12.0%). Cirrhotic cardiomyopathy was observed in 41.0% patients with cirrhosis. There was statistically insignificant difference in the observed frequency of cirrhotic cardiomyopathy among various subgroups of cirrhotic patients depending upon patient’s age (p-value=0.928), gender (p-value=0.997), BMI (p-value=0.983) and duration of disease (p-value=0.782). However, it increased considerably with worsening of disease on CTP Classification; Class-A vs. Class-B vs. Class-C (8.3% vs. 35.9% vs. 53.1%; p-value=0.013). Conclusion: Cirrhotic cardiomyopathy was observed in a substantial proportion of cirrhotic patients and was more frequent in patients with more severe disease which warrants routine echocardiographic screening of cirrhotic patients so that timely recognition and anticipated treatment of this complication may improve the case outcome in future medical practice. Keywords: Cirrhosis, Cardiomyopathy, Child Turcotte Pugh Class