Study Cardiac Dysfunction as an Early Predictor of Esophageal Varices in Patients with Liver Cirrhosis ‎

• Due to the increased mortality and danger of bleeding, the presence of esophageal varices (EV) caused by portal hypertension is a serious concern in cirrhotic patients.
• EGD is an invasive, unpleasant procedure that occasionally has serious complications.
• LV mass index, E-wave deceleration time, LA volume, E/A ratio and ratio E/È were significantly increased among cirrhotic group with oesophageal varices than non-cirrhotic group without E.V.
• TDI did not significantly differ across the examined groups.
• Cardiac dysfunction though being a neglected entity can be used dependably for prediction of portal hypertension.

Numerous studies have tried to determine whether the existence esophageal varices may be detected by non-invasive measures, eliminating the requirement for screening endoscopy in all cirrhotic patients [3]. However, there is no universal consensus on the optimum variable for predicting EV risk [4]. In the absence of any other known causes of cardiac illness, cirrhotic patients frequently develop cirrhotic cardiomyopathy, a kind of chronic heart disease characterized by altered diastolic relaxation and/or impaired contractile response to stress [5]. Diastolic dysfunction has been associated with larger left ventricular (LV) walls, subendocardial edoema, fibrosis, and altered collagen structure, which finally leads to aberrant relaxation in cirrhotic individuals [6].

Table 1: Esophageal varices grades in relation to sociodemographic, clinical data and vital signs among the studied groups.

According to the evidence that is currently available, liver cirrhosis is commonly ignored until complications such as ascites, spontaneous bacterial peritonitis (SBP), variceal haemorrhage, or hepatic encephalopathy manifest themselves [17]. Nearly half of all cirrhotic patients had EV at the time of diagnosis. Varices expand from tiny to large at a rate of 5–12% per year, and once they have formed, they bleed at a rate of 5–12% per year [18]. Numerous studies have shown that when liver cirrhosis is found, patients should be checked for the presence of EV. However, endoscopy is an invasive and unpleasant procedure that can have uncommon but serious side effects [4].

Patients with liver cirrhosis may experience cirrhotic cardiomyopathy, a kind of chronic heart dysfunction that is defined by altered diastolic relaxation and/or decreased contractile responsiveness to stress in the lack of any other previously recognised causes of cardiac disease. Latent cardiac failure is the term used to describe cirrhotic cardiomyopathy. But more research is needed to determine whether cardiac dysfunction exists even while the patient is at rest [19,20]. Increased left ventricular (LV) wall thickness, subendocardial edoema, fibrosis, and altered collagen structure have all been linked to diastolic dysfunction in cirrhotic individuals, which eventually affects relaxation [21].

Cirrhosis-related cardiovascular alterations affect prognosis. Therefore, the assessment of subclinical cardiac involvement could aid in the early identification of cirrhotic individuals who are more likely to decompensate and experience complications, enabling more effective follow-up care [22]. Therefore, the goal of this study was to evaluate the cardiac dysfunction in cirrhotic patients and relate endoscopic evidence of portal hypertension with cardiac involvement using echocardiographic indicators of diastolic dysfunction. Between Journey 2021 and Journey 2022, a clinical trial research study including 40 patients with a confirmed diagnosis of liver cirrhosis and a control group of 20 volunteers of a matched age and sex was conducted to clarify our findings.

Considering electrocardiographic evaluation among the studied groups, we demonstrate that the QTc interval was considerably longer in all cirrhotic patients when compared to the control group. We also noticed that QTc interval did not differ significantly between cirrhotic patients with high and low grades of esophageal varices, however still a trend in high esophageal varices grade group to show a higher value.

A measurement of ventricular repolarization is the length of the QT interval as estimated by 12-lead electrocardiography. Ventricular repolarization abnormalities may be the basis for ventricular arrhythmia and sudden death; as a result, they are crucial for both ECG diagnosis and therapeutic decision-making [23]. At first, Patients with alcoholic cirrhosis had longer QT intervals and rapid deaths; later, it was further clarified in cirrhosis of other etiologies, coupled with the severity of the illness, the emergence of portosystemic shunts, and poor survival [24]. Nevertheless, well-compensated liver illness can also be observed as having a longer QTc interval [25].

The cause of the QT interval's extension is still a question. Modifications at the molecular level had been proposed. Other causes involve myocardial ischemia, altered electrolytes, and changes in the autonomic nervous system that may affect the heart rate and electromechanical coupling via a variety of mechanisms. Additionally, in advanced cirrhosis, abnormalities in gonadal hormone metabolism have been proposed to have a role in the development of QT prolongation [26].

On the echocardiographic evaluation, the findings of this study showed that cirrhotic patients had considerably higher LA volume, LV mass index, E-wave deceleration time, atrial (A wave) flow velocities, E/E′ ratio, and E/A ratio values than the control group. Yet, when comparing individuals with high grade esophageal varices to those with low grade esophageal varices, only the LA volume was considerably larger and Ratio E/E′ was significantly lower. Additionally, there were no notable variations in TDI, peak early (E wave), A velocity, or E velocity across the groups under study.

Our results are near to those of Marconi et al. study, which indicates that echocardiographic parameters including LA volume, LV mass index, and TDI S′-wave velocity may be beneficial in predicting the existence of esophageal varices [27]. They verify that patients with compensated cirrhosis have left atriums (LA) that are significantly larger, as determined by either the volume index or the AP diameter, and that the only independent indicator of LA enlargement is liver stiffness (LS). Furthermore, Merli et al. previously documented LA enlargement in cirrhotic individuals, along with an increase in LV diameters but not volumes [28].

Being a stronger predictor of chronic diastolic dysfunction, the LA enlargement reflects the effects of elevated filling pressures over time, regardless of hemodynamic changes. In the course of cirrhotic cardiomyopathy, LA enlargement may be used as a diagnostic marker for diastolic dysfunction [27]. additionally, Njideoforet al.found that CLD patients had a larger left atrial diameter, a higher LVMI that was related with diastolic dysfunction, and retained systolic performance at rest [29].

However, Kazankov et al.reported that the E/A ratio did not significantly differ between the cirrhotic and non-cirrhotic groups. Patients with cirrhosis who were primarily alcohol-related had increased left ventricular wall thickness, mass, and volumes [19]. These results might be a part of the well-known condition (alcoholic cardiomyopathy) in that particular group of patients. In such circumstances, the toxicity of ethanol is connected to cardiac hypertrophy and contractile dysfunction [30]. Besides, calculating tissue velocity and TDI in our investigation using the four-chamber apical view.

To evaluate its performance, the lateral mitral annulus' cardiac peak systolic velocity (S′) was recorded. Because all patients were selected with an EF of more than 55%, indicating that there was no systolic dysfunction in these people, there is no discernible difference in TDI across the tested groups. This finding is in line with the findings of Bodys-Peka et al. who has reported that systolic dysfunction in cirrhotic individuals is primarily latent [31]. Furthermore, Marconi et al.study’s revealed no variations in ventricular volumes or thicknesses, albeit the latter result may have been skewed by excluding outpatients with alcoholic cirrhosis from our group, which has been associated with altered LV diameters [27]. They were unable to link the Doppler trans mitral flow analysis results of the E/A ratio, deceleration time, and E/E′ to the level of liver fibrosis.

The ROC curve was applied to identify the sensitivity of electrocardiographic and echocardiographic finding to predict cardiac dysfunction in cirrhotic group and discriminating between cirrhotic and non-cirrhotic groups. The QTc interval, E-wave deceleration time and Ratio E/A had highest accuracy. This is in line with the findings of Somani et al.who found that the ratio of early-to-late diastolic filling (E/A) is the most often utilized metric and that cirrhotic individuals have lower E/A ratios than controls [32]. The Montreal definition's diagnostic criteria now include an E/A ratio of 1. This agrees with De et al.,who discovered that non-cirrhotic portal fibrosis also exhibits diastolic impairment. It suggests that the development of heart dysfunction is strongly influenced by portal hypertension [33].

Furthermore, we utilized the ROC curve to identify the applicability of electrocardiographic and echocardiographic finding to discriminate patients with high grade esophageal varices from those with low ones, we noticed that LA volume, Ratio E/È and QTc interval had the highest accuracy.  Even though multiple studies have been undertaken, EGD is currently the screening approach for all cirrhotic patients because no other noninvasive procedures have demonstrated an acceptable predictive value for signs of portal hypertension.

In a study by Marconi et al., who examined the relationship between echocardiographic and EGD data, they revealed that the existence of esophageal varices tends to be closely related to the cardiovascular alterations associated with cirrhotic cardiomyopathy [27]. In addition, a decrease in the peak S′-wave velocity on TDI, an increase in LV mass, and LA dilatation may be early indicators of portal hypertension and may be helpful for the early identification of patients who are at a higher risk of portal hypertension and its associated complications. Compared to liver elastography, echocardiography appears to perform better as a predictor of endoscopic findings of portal hypertension [30].

CONCLUSION

Despite being a frequent condition, cardiac dysfunction is the area of clinical examination ‎that receives the least attention. Therefore, all cirrhotic individuals should have their heart ‎function evaluated. Echocardiographic indicators of diastolic failure in liver cirrhosis include E-‎wave deceleration time, left atrial enlargement, E/E′, LV mass index, and E/A ratio. Cardiac ‎changes are closely related to endoscopic finding of portal hypertension. Possible early warning ‎signs of heart malfunction include QTc prolongation. A left atrium enlargement, a considerable ‎increase in E/E′, LV mass index, E/A ratio, and E-wave deceleration time are all characteristics ‎of cirrhotic individuals‎.

The present study has limitations, including its relatively small sample size and lack of a stress ‎test (such as one involving physical exertion or a pharmacological), which would have revealed ‎subclinical systolic dysfunction more clearly. Secondly, we currently lack prospective data that ‎would allow us to assess the potential use of echocardiographic findings as prognostic ‎indicators for patients with portal hypertension‎.

Abbreviations: 

ECG: Electrocardiographic

EV: Esophageal varices

HVPG: Hepatic venous pressure gradient

MAP: mean arterial pressure

DBP: Diastolic blood pressure

SBP: Systolic blood pressure

BMI: body mass index

WBCs: White blood cells

Hb: Hemoglobin

INR: international normalized ratio

AST: Aspartate aminotransferase

ALT: Alanine transaminase

E: E wave,

A: A wave,

TDI: Tissue Doppler imaging,

LV: Left ventricle,

LA: Left atrial

Ethical consideration: After outlining the purpose of the study, each participant was given information about it and given the opportunity to give their informed permission before being enrolled in the study. The institutional and/or national research committee's ethical requirements were followed in all procedures. The Menoufia University Committee on Human Rights in Research approved the project (IRB 8/2018 TROP40)   and it was performed in accordance with the Helsinki Declaration.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable. The study was fully non-funded from any organization.