Comparison of B Type Natriuretic Peptide and ‎Echocardiographic Findings among Patients ‎with Various Stages of Liver Diseases

Troponin-I, atrial natriuretic peptide (ANP), and B type natriuretic peptide (BNP), were elevated in cirrhotic patients, which may be explained by the hyperactivity of the renin-angiotensin-aldosterone system resulting in indirect diastolic dysfunction [6]. There is limited information regarding the exact definition, prevalence, diagnosis, and management of this syndrome, which requires more robust research [7]. Our study aims to determine prevalence of cirrhotic cardiomyopathy among Egyptian chronic liver disease patients as well as to identify the best methods for early diagnosis.

DISCUSSION

Patients having stable liver disease typically possess minor myocardial dysfunction that ‎may not be obvious during a routine examination. However, a cardiac manifestation of ‎liver cirrhosis may present either as the disease progresses or in the presence of ‎physiological/ pharmacological stress [7]. During the last years, several studies have ‎concentrated their attention on the existence of specific cardiac abnormalities in cirrhotic ‎patients.‎

In this cross-sectional study, we evaluated cardiac functions of 72 cirrhotic patients using ‎echocardiography and ECG in addition to serum BNP level.  ‎

In our study, liver cirrhosis was more prevalent in males holding 54.6 ± 9.3 years as mean ‎age. This is comparable to studies done in other countries. Similarly, Kumar et al. reported ‎that 78% of 90 cirrhotic patients were males having 46.2 ± 10.8 years as mean age [10]. ‎Bhatti et al. stated that 58% of 166 cirrhosis patients were male, having a mean age of ‎‎57.05 ± 12.03 years [11].‎

The Egyptian demographic health survey demonstrated an increased viremia prevalence ‎with age and gender (particularly males) [12]. In Egypt, hepatitis C virus (HCV) is mostly ‎prevalent among lower socioeconomic groups [13]. In our study, the most prevalent CLD ‎etiology was hepatitis C infection, which was expected since hepatitis C is hyperendemic in ‎Egypt. The majority of our patients resided in rural areas (75%), which may be associated ‎with the higher prevalence of hepatitis C and bilharziasis in these areas. It should be noted ‎that even though cirrhotic cardiomyopathy is clinically unremarkable at rest, during ‎stressful conditions such as exercise, infections, specific medications, hemorrhage, as well ‎as any intervention, such as the insertion of TIPS, and liver transplantation, which may ‎result in the conversion of latent cirrhotic cardiomyopathy into heart failure [14].‎

There is a need for more accurate and alternative screening tests in order to determine the ‎severity of cirrhotic cardiomyopathy, which may prove useful in managing liver cirrhosis ‎patients. Considering the gradual course of cirrhotic cardiomyopathy, there may be a ‎benefit to using new laboratory markers, ECG, in addition to echocardiography, mainly in ‎combination [15]. One of the electrophysiological abnormalities found in cirrhotic patients ‎is prolonged repolarization, which manifests as a prolonged QTc interval. This finding was ‎demonstrated in our cirrhotic patients. A strong positive correlation existed between QTc ‎and advanced Child class (r = 0.6, p <0.0001), degree of diastolic dysfunction (r = 0.373, p ‎‎= 0.001), and LT atrium diameter (r =0.312, p<0.008). ‎

We found that diagnostic accuracy of QTc duration for discrimination between ‎compensated (Child A) and decompensated liver cirrhosis (child B + C) revealed an AUC ‎of 0.81 (95% confidence interval [CI], 0.707 – 0.897), with 91.6% sensitivity (95% CI, ‎‎80.0 - 97.7), and a specificity of 58.3% (95% CI, 36.6 – 77.9).  ‎

Our results are consistent with previously published studies, which found that QTc ‎prolongation is prevalent among cirrhotic patients and directly correlated with liver ‎dysfunction severity (Child-Pugh score), ascites, in addition to portal hypertension .‎

Prolonged QT interval and defective electromechanical coupling found in cirrhotic patients ‎was linked to a volume overload [16], as well as a combination of ion-channel dysfunction, ‎autonomic dysfunction, plasma membrane abnormalities, in addition to receptor-related ‎pathway defects [17].

Diastolic dysfunction is defined as failure of left ventricular relaxation, which impedes ‎blood flow through ventricle, thereby an increase in left ventricular end-diastolic ‎pressure [18].

Using conventional Doppler echo, we found that different grades (grade I- II) of diastolic ‎dysfunction existed in most cirrhotic patients (82%). A significant difference existed among ‎patients in different child groups (p>0.008), correlated with cirrhosis severity.‎

‎ Our study demonstrated that increased Lt atrium diameter (OR, 7.96; 95% CI, 2.11–30.07, ‎p = 0.002), advanced Child class (OR, 13.80; 95% CI, 1.58–120.38, p = 0.0017), ‎increased BNP level (OR, 5.56; 95% CI, 1.51–20.51, p = 0.001), and prolonged QTc ‎duration (OR, 10.12; 95% CI, 1.24–82.96, p = 0.03) were significant predictors for ‎diastolic dysfunction. ‎

Møller and colleagues found that many patients with cirrhosis exhibited various diastolic ‎dysfunction degrees. Diastolic dysfunction in cirrhosis patients may be explained by ‎increased myocardial wall stiffness resulted from myocardial hypertrophy, fibrosis, as well ‎as subendothelial edema, which further results in elevated left heart (atrium and ventricle) ‎filling pressures [7]. LV hypertrophy results in impaired diastolic relaxation, leading to ‎lowered compliance and higher diastolic pressures [19]. ‎

Another research assessed HCV cardiovascular impact on Egyptian patients and noticed a ‎significant increase in diastolic dysfunction among patients [20]. This goes in accordance ‎with our findings. ‎

There is limited evidence that supports pathogenesis of cirrhosis induced diastolic ‎dysfunction.  It is suggested that the cardiac impairment may be as a result of collagen ‎configuration alteration, sodium retention in addition to activation of renin aldosterone ‎system [21].‎

Diastolic dysfunction may progress to systolic dysfunction [22]. At rest, systolic function is ‎either normal or increased in most cirrhotic patients, along with hyperdynamic circulation ‎highlighted by elevated cardiac output as well as tachycardia. Stressors ‎‎(pharmacological/ physiological) may exacerbate underlying systolic dysfunction in this ‎patient group [23].‎

Our study found statistically significant differences in Ejection fraction between Child A ‎and Child B group patients (p-value = 0.028).‎

Pagourelias et al. found that EF was significantly higher in cirrhosis patients (77 men) in ‎comparison to the controls (20 healthy), which was accounted for by increased blood ‎volume and cardiac adaptation [24].‎

Ziada and coworkers demonstrated that LVEF% has no difference among cirrhotic groups ‎as well as controls [25]. Moreover, Eldeeb and coworkers stated that mean left ventricular ‎systolic function parameters exhibited within normal range among the three Child groups’ ‎patients [26]. Systolic function is maintained in patients with cirrhosis with normal or even ‎the presence of elevated ejection fraction at rest [14], as reported by Baik et al.‎

Lt atrial dilatation was seen in most of our studied patients, with significant difference ‎among patients in different Child groups (p-value = 0.001, <0.0001) between Child A and ‎B, Child B and C, respectively. Dilation was linked to cirrhosis severity. These findings ‎were in line with studies conducted by Wong et al. and Pozzi et al. [23, 27]. ‎

Cardiac natriuretic peptides are considered markers of volume overload and cardiac ‎dysfunction.  Several researches have demonstrated that cirrhotic patients have elevated ‎plasma concentrations of BNP as well as NT-pro-BNP, suggesting their use as markers of ‎early cardiac dysfunction in cirrhotic patients [28]. ‎

Regarding levels of BNP among the three study groups, a statistically significant difference ‎was indicated and higher in Child C group patients (p<0.001).  BNP levels augmented with ‎cirrhosis severity. ‎

In this study, BNP was found to be a valid marker toward diastolic dysfunction in patients ‎with cirrhosis (p<0.002, 95% CI 0.63–0.84), exhibiting 66.1% sensitivity and 84.6% ‎specificity, at 78 pg./ml cutoff value.‎

The diagnostic accuracy of circulating BNP for discrimination of between compensated ‎‎(Child A) and decompensated liver cirrhosis (Child B + C) revealed an AUC of 0.78 (95% ‎confidence interval [CI], 0.671 - 0.872), with 79.1% sensitivity (95% CI, 65.0 - 89.5), a ‎specificity of 83.3% (95% CI, 62.6 - 95.3).‎

Our study demonstrated that HCV-related disease (OR = 0.24; 95%CI, 0.08–0.75, p = ‎‎0.013), diastolic dysfunction (OR, 5.56; 95% CI, 1.51–20.51, p = 0.01), increased LT ‎atrium diameter (OR, 23.62; 95% CI, 6.30–88.54, p = 0.0001), and advanced child class ‎‎(OR, 10.0; 95% CI, 2.54–39.29, p = 0.0009) are significant predictors for increased BNP ‎level. Another study done in Egypt showed that BNP level was significantly higher in ‎patients with cirrhosis than controls, but liver disease state, whether compensated or not, ‎had no effect on its level [29]. Other researchers reported association between the level of ‎BNP and pro-BNP and liver disease severity [30].‎

In multivariate analysis, adjusted for diastolic dysfunction, liver disease etiology, and Child ‎C, risk of increased BNP was 18 times higher in patients Grade I-II LT atrium diameter ‎than patients with normal diameter (OR, 18.17; 95% CI, (3.93–84.05, p = 0.0002), table ‎‎(3).‎

Our findings are consistent with those of preceding researches, indicating that BNP level ‎was significantly elevated with liver cirrhosis degree, liver failure, in addition to portal ‎hypertension [30]. ‎

CONCLUSION

Our findings suggest that cardiac dysfunction is directly proportional to cirrhosis severity ‎and linked to electrophysiological, echo-cardiographic, in addition to laboratory changes. ‎Diastolic dysfunction, as well as Lt atrial dilatation, are mostly prevalent cardiac ‎abnormalities, worsening with cirrhosis development. BNP is a highly specific and ‎sensitive marker, and may be utilized toward the early detection of cardiac dysfunction in ‎patients with cirrhosis.‎

Funding: ‎none declared.

Conflict of interest: ‎none declared.

Ethical considerations :

-confidentiality was assured.

-every individual was asked for a permission to do interview.

-examination steps of interview and examination was explained to the patient.

-patients faced no physical or psychological risks