The Study Of Cardiac Function And Its Influencing Factors In Patients With Liver Cirrhosis

BackgroundAs early as in1953, Kowalski found that there were cardiac dysfunction in patients with liver cirrosis for the first time.Then many research further confirmed the cardiovascular system in patients with cirrhosis or portal hypertension was abnormal. The circulation becomes hyperdynamic, characterized by increased cardiac output and decreased peripheral vascular resistance and arterial pressure. Moreover, despite the increased cardiac output at rest, with stressful stimuli such as hemorrhage, surgery or vasoactive drug administration, the ventricular response is blunted, a condition known as cirrhotic cardiomyopathy(CCM).These cardiovascular abnonnalities have been suggested to induce or aggravate several complications of cirrhosis such as renal salt and water retention, variceal bleeding,hepatopulmonary syndrome, and increased cardiovascular fragility under stress. Further more, the disfunction of heart could affect the prognosis of patients with liver cirrhosis.In a study of70patients with refractory ascites, half treated with transjugular intrahepatic portosystenic stent shunt (TIPSS) and the other half treated with repeated large volume paracentesis,12%patients in the former group developed cardiac failure,compared to none in the latter group. Also in the study reported by Schwartz,about13%of patients with liver cirrhosis appeared the signs and symptoms of heart failure after transjugular intrahepatic portosystenic stent shunt (TIPSS).Liver transplantation(LT) exerts enormous stresses on the heart, heart-related complications that can occur in the post-operative period include reperfusion syndrome, arrhythmias, sudden cardiac death, myocardial infarction and heart failure. But because of the marked peripheral vasodilatation characteristic of cirrhosis, the ventricular afterload is reduced. In other words, the cirrhotic patient is almost autoprotected from developing severe or overt heart failure, at least in the absence of a major cardiovascular challenge.So cirrhotic cardiomyopathy(CCM) does not cause the attention of clinical physicians.Looking for a effective index to monitor the cardiac dysfunction in patients with liver cirrosis have great clinical significance. Brain natriuretic peptide (BNP) is one of the important indicators to evaluation cardiac function.The United States and the European heart association recommend BNP as laboratory index to evaluation cardiac dysfunction.Some researches have founded that plasma BNP levels in patients with liver cirrhosis have close relation with liver function and the cardiac dysfunction, may be one of the potential diagnosis symbols of cirrhotic cardiomyopathy(CCM). In Yildiz’s study, fifty-two non-alcohol cirrhotic patients were detected BNP and cardiac echocardiographic, a significant correlation was observed between BNP concentration and Child-Turcotte-Pugh(CTP) score,interventricular septal thickness and left ventricular posterior wall thickness.Plasma BNP levels were significant higher in Child class B and C patients compared with class A patients.Increased levels of BNP were more likely related to the severity of disease in cirrhotic patients.The advanced cirrhosis was associated with more advanced cardiac dysfunction and BNP had prognostic value in progression of cirrhosis. Henriksen’s research also confirmed plasma BNP and proBNP were significantly increased in cirrhotic patients compared with age matched controls and healthy subjects.Circulating BNP and proBNP were close related to severity of liver disease(Child-Turcotte-Pugh score,serum albumin,hepatic venous pressure gradient) and to markers of cardiac dysfunction(QT interval,heart rate,plasma volume)but not to indicators of the hyperdynamic circulation.Elevated circulating levels of BNP and proBNP in patients with cirrhosis most likely reflected the presence of cardiac dysfunction. In conclusion, the detection of BNP may help to found cardiac dysfuntion in patients with cirrhosis.But NT-proBNP(N-terminal pro-brain natriuretic peptide) has been recently suggested to be a even better indicator of early cardiac dysfunction than BNP because of its stability and longer biological half-life.In Jeong’s study,plasma NT-proBNP levels were high in cirrhotic patients and were likely to be related to the severity of disease.Advanced cirrhosis was associated with advanced cardiac dysfunction,and NT-proBNP levels had predictive value for concomitant cardiac dysfunction and cirrhosis progression.Cirrhotic cardiomyopathy(CCM) as a recently proposed complication of cirrhosis, because of its clinical manifestation conceals, and lacking of specific diagnosis and treatment measures, have not get enough attention of clinical physicians. Our research aims to deepen the understanding of cirrhotic cardiomyopathy, search sensitive index of cirrhotic cardiomyopathy.So our research divide into two parts.The first part we investigate the cardiac function by echocardiography and the correlation with liver functon in cirrhotic patients, analysis its influencing factors to cardiac function. The second part, we detect serum NT-proBNP concentration of patients with liver cirrhosis, analysis the relationship between serum NT-proBNP concentration and the function of liver and the parameters of cardiac echocardiography, explore that NT-proBNP levels whether have predictive value for cardiac dysfunction and cirrhosis progression.Part1:The study of cardiac function by echocardiography and its influencing factors in patients with liver cirrhosisObjective To investigate the cardiac function by echocardiography and the correlation with liver functon in cirrhotic patients, analysis its influencing factors to cardiac function.Methods A total of70cirrhotic patients and25healthy controls were studied by two dimensional Doppler echocardiography.70cirrhotic patients were divided into group A, B and C(Child A group, Child B group and Child C group) according to the Child-Pugh score(22patients were Child class A,29patients were Child class B,19patients were Child class C). Cardiac dimensions and left and right ventricular functions were evaluated. All of the patients were conducted detection of routine blood, kidney and liver function, coagulation function before treatment. Data were expressed as mean+SD.Comparison between liver cirrhosis group and control group was performed by two-sample t-test. Comparison between Child A group, Child B group and Child C group was performed by a standard one-way analysis of variance. The Spearman correlation was used to analysis the relationship between different factors. A p value <0.05(two-tailed) was considered to be significant. All calculations were processed using the SPSS17.0software package.Results Comparison between cirrhotic patients and healthy controls,we discovered that LVd,LAs,LVPW, and AAO were increased as compared with that in the latter group,whereas the value of E/A was reduced(LVd:43.15±4.38mm vs41.38±2.93mm,(P=0.029);LAs:31.34±3.94mm vs27.52±2.69mm(P=0.000);AAO:28.76+2.99mm vs26.25+2.63mm(P=0.000);LVPW:9.86±1.04mm vs9.36+0.76mm(P=0.032);E/A:1.02+0.33vs1.19+0.35(P=0.033);) There were no significant difference between the Child A,B and C group for LVd, LVPW, AAO and the value of E/A.Compared the data of LAs in each group showed that Child A(31.10+4.14mm)<Child C(33.81+4.06mm) and Child B(29.91+2.91mm)<Child C(33.81+4.06mm)(P=0.013and P=0.000,respectively), but there was no significant difference between A and B group(P=0.223). According to the age, patients with liver cirrhosis were divided into groups of less than50years old,50-59years old,60years old or above. There was no significant difference between the three groups for LAs. By comparison between different ascites group,we found that LAs in patients with moderate-to-severe ascites increased than that in patients without ascite and patients with a few ascites. On the contrary, E/A ratio decreased. Correlation analysis showed that there was positive correlation between LAs and the levels of creatinine and there was negative correlation between E/A ratio and the levels of creatinine.Conclusion The cardiac systolic and diastolic function of patients with cirrhosis are deficient,and diastolic dysfunction is given priority to systolic dysfunction.The cardiac dysfunction confirmed the existence of cirrhotic cardiomyopathy. The degree of cardiac insufficiency is related to the damage of liver function, large ascites.We should pay attention to the possibility of cirrhotic cardiomyopathy if LAs increases, E/A<1. Part2:The serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with cirrhosis:relation to cardiac dysfunction and liver functionObjective Subtle cardiac abnormalities have been described in patients with cirrhosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) have been reported to be sensitive makers of early cardiac disease. The aim of our study was to evaluate the levels of NT-proBNP and the relationship with cardiac structure and function which was evaluated by echocardiography in patients with cirrhosis. Furthennore,we analysed the relationship between the levels of NT-proBNP and liver function.Therefor the aim of our study was to clarify the status of the NT-proBNP as makers of cardiac dysfunction in cirrhosis.Methods A total of50cirrhotic patients were studied by two dimensional Doppler echocardiography. Cirrhotic patients were divided into group A, B and C according to the Child-Pugh score(15patients were Child class A,20patients were Child class B,15patients were Child class C). Cardiac dimensions and left and right ventricular functions were evaluated. At the same time,we detected the serum NT-proBNP of50cirrhotic patients and11healthy controls.Data were expressed as mean±SD.Comparison between liver cirrhosis group and control group was performed by two-sample t-test. Comparison between Child A group, Child B group and Child C group was performed by a standard one-way analysis of variance. The Spearman correlation was used to analysis the relationship between different factors. A p value <0.05(two-tailed) was considered to be significant. All calculations were processed using the SPSS17.0software package.Results Comparison between cirrhotic patients and healthy controls, the levels of serum NT-proBNP in cirrhotic patients was higher than that in healthy controls (161.87+69.07pg/ml vs87.29+32.14pg/ml, P=0.000).There were no significant difference between the A,B and C group for LVd, RVd、IVS、LVPW、E wave A wave、AAO and the value of E/A.As for LAs, A group(31.74±4.04mm)<C group(34.97±3.58mm),P=0.015; B group(29.75±3.03mm)<C group(34.97±3.58mm),P=0.000;but there was no significant difference between A and B group.Then comparison the the levels of serum NT-pro BNP showed that A group (124.19±50.13pg/ml)<C group (222.87±76.25pg/ml),P=0.000; B group (144.38±42.28pg/ml)<C group (222.87±76.25pg/ml),P=0.000; there was no significant difference between A and B group(P=0.302). Correlation analysis showed that NT-proBNP had positive correlation with LAs and LVPW(r=0.540,P=0.000and r=0.309,P=0.029). In addition,we also found that NT-proBNP had close correlation with Child-Turcotte-Pugh score (r=0.454,P=0.001),the levels of albumin (r=-0.376,P=0.007) and the levels of total bilirubin (r=0.283, P=0.047)Conclusion Increased levels of serum NT-proBNP have significant clinical implications in patients with cirrhosis because it was found to be related to disease severity. Further more, it may be suggested that cardiac dysfunction is related to an increased serum NT-proBNP levels, and that NT-proBNP has predictive value in cases of concomitant cardiac dysfunction and cirrhotic progression.