Results

Table 1 summarises the results of the echocardiographic examination before and nine hours after the stent implantation. Before TIPS, left atrial diameter, left ventricular end diastolic volume, stroke volume, and cardiac output were distinctly above the upper normal limit. Left ventricular end systolic volume and left ventricular ejection fraction were within the upper limit of the normal range. Nine hours after the TIPS procedure a significant increase in left atrial diameter (2.5 (1.5) mm; 6%), left ventricular end diastolic volume (11.0 (13.1) ml; 7%), stroke volume (12.2 (12.1) ml; 12%), cardiac output (1.27 (1.13) l/min; 16%), and left ventricular ejection fraction (3.2 (2.6)%; 5%) was found. The cardiac output before and nine hours after TIPS, calculated by two dimensional echocardiography (7.9 (1.7) v 9.1 (2.2) l/min), was comparable with the corresponding invasively determined values (8.5 (1.7) v 10.0 (1.7) l/min) (fig1).

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Figure 1

Time course of cardiac output (CO), systemic vascular resistance (SVR), and total pulmonary resistance (TPR) before and within nine hours of a transjugular intrahepatic portosystemic stent shunt (TIPS) in nine patients with portal hypertension. Values are expressed as mean (SD).

Table 2 summarises the haemodynamic data obtained with the Swan-Ganz catheter before and after TIPS. TIPS implantation induced a significant sharp rise in heart rate (change 9.5 (10.1) beats/min; 13%), systolic blood pressure (16.8 (23.1) mm Hg; 15%), and right atrial pressure (5.9 (2.6) mm Hg; 101%), whereas the diastolic blood pressure did not change significantly. Systolic (change 15.3 (5.5) mm Hg; 81%), diastolic (9.7 (4.8) mm Hg; 107%), and mean (12.8 (5.3) mm Hg; 92%) pulmonary artery pressures, as well as pulmonary capillary wedge pressure (10.5 (4.0) mm Hg; 111%), cardiac output (3.7 (1.6) l/min; 47%), stroke volume (30.5 (14.5) ml; 28%), and total pulmonary resistance (48.3 (43.7) dyn·s·cm⁻⁵; 34%) increased significantly. Systemic vascular resistance decreased significantly (change 226 (171) dyn·s·cm⁻⁵; 27%).

In the subgroup of nine patients for whom the period of catheter measurements was extended to nine hours, immediate haemodynamic changes comparable with the main study group were observed after the TIPS procedure. During the nine hour follow up period, the pulmonary artery pressures, the right atrial pressure, and the cardiac output returned towards the preshunt values, but remained significantly elevated (change at nine hours: mean pulmonary artery pressure, 4.0 (2.4) mm Hg, 27%; pulmonary capillary wedge pressure, 2.6 (3.1) mm Hg, 27%; right atrial pressure, 2.5 (2.5) mm Hg, 39%; cardiac output, 1.4 (1.3) l/min, 16%). The systemic vascular resistance remained significantly reduced (change at nine hours: 219 (129.8) dyn·s·cm⁻⁵, 27 %), whereas the total pulmonary resistance did not differ significantly from preshunt values (table 2, fig 1).

Table 3 compares the haemodynamic variables in the splanchnic and systemic circulations of the subgroup of nine patients before and nine hours after the TIPS procedure. The shunt resulted in a significant reduction in portoatrial pressure gradient (change 8.8 (2.7) mm Hg; 43%) and the portohepatic vascular resistance (1370 (357) dyn·s·cm⁻⁵; 72%). Portal vein blood flow increased significantly (1.4 (0.53) l/min; 127%).

Discussion

The baseline echocardiographic data suggest an alteration in the diastolic, but not the systolic, left ventricular function in the patients with alcoholic cirrhosis. These findings are supported by another echocardiographic study18 of cirrhotic patients, mainly chronic alcoholics, with an elevated left ventricular end diastolic volume index, whereas the left ventricular end systolic volume index was almost unchanged compared with healthly adults. In contrast, Askansis et al 19showed increased end diastolic and end systolic left ventricular volumes in chronic alcoholics, indicating an additional systolic dysfunction. Estruch et al 20observed increased left ventricular end diastolic diameters in active alcoholics, but not in non-alcoholic cirrhotic patients. Dancyet al 21 found that the increased left ventricular dimensions observed in alcoholics were directly related to alcohol, but were independent of the presence and severity of liver disease.

Liver cirrhosis is characterised by a hyperdynamic circulation, with an increased cardiac preload22 and a decreased cardiac afterload.23 For healthy hearts, the diastolic filling of the left ventricle and the systolic emptying would be enhanced under these haemodynamic conditions. However, in rats with cirrhosis, a limited cardiac preload reserve was shown.22 Our echocardiographic findings and the additional catheter data support the existence of a similar haemodynamic situation in our patients with alcoholic cirrhosis. The increased right atrial pressures up to nine hours after the intervention indicate that the acute blood volume shift from the splanchnic to the systemic circulation induced by the TIPS procedure exceeds the filling capacity of the right ventricle. The persistent increase in the pulmonary capillary wedge pressure and the significantly increased left atrial diameter nine hours after the intervention indicates a diminished left ventricular preload reserve, which triggers secondary effects on the pulmonary circulation. These are reflected in a persistent moderate increase in the pulmonary artery pressures and the total pulmonary resistance. However, the fact that right atrial pressure, pulmonary artery pressures, pulmonary capillary wedge pressure, and total pulmonary resistance returned towards the baseline value during the nine hour follow up period indicates extensive cardiac compensation by rapid distribution and excretion of the shunted blood volume.

Another factor that may influence the haemodynamic effects of the TIPS procedure is the impairment of β-adrenergic receptor function in cirrhotic cardiomyopathy.6 ,24 It has been well recognised that blood noradrenaline levels are elevated in cirrhotic patients25 ,26 and that baseline noradrenaline levels correlate positively with the severity of the cirrhosis.3Elevation of the sympathetic tone may be responsible for the decreased β₂-adrenergic density in circulating lymphocytes of cirrhotic patients27 and in cardiomyocyte plasma membranes in the cirrhotic rat model.28 ,29 These findings are assumed to play a causal role in the inadequacy of the heart rate increase to compensate for the increased cardiac preload found after the creation of a TIPS.

It has been hypothesised that a portosystemic shunt may diminish the hepatic clearance of gut derived vasoactive agents30—for example, endotoxin31—which contribute to the activation of nitric oxide synthase of endothelial and smooth muscle cells.32-34 In addition, a further increase in the concentration of glucagon and other mediators, such as prostaglandins and vasointestinal polypeptides, may contribute to a shunt induced diffuse vasodilatation.35 ,36 These vasoactive agents have been reported to be additional relevant factors influencing the pulmonary and systemic circulations after creation of a portosystemic shunt. However, the differential effects of the shunt-induced blood volume shift on the pulmonary and systemic circulations argues against a predominant role for these humoral factors in the haemodynamic changes after TIPS in our study. One would expect that these vasoactive substances, once eliminated by hepatic clearance, would affect the systemic and pulmonary vascular beds in the same way.

In our patients, the increase in portal vein blood flow (1.4 l/min; table 3) nine hours after the TIPS implantation was associated with a comparable increase in cardiac output (1.5 l/min; table 2). These haemodynamic changes were associated with a substantial reduction in the portohepatic vascular resistance (72%; table 3) and the systemic vascular resistance (27%; table 2). Thus one major explanation for the persistent decrease in systemic vascular resistance after TIPS implantation is assumed to be the haemodynamic effects of the shunt itself. Our data suggest that the fall in portohepatic vascular resistance after the creation of a portosystemic stent shunt in portal hypertension is mainly responsible for the further decrease in the systemic vascular resistance. This effect on systemic vascular resistance, which has been confirmed in other studies,37 ,38 may be of great clinical importance because of its possible negative effects on renal function.

In contrast with these effects on the systemic circulation, there are somewhat conflicting results on the effects of TIPS on the pulmonary circulation. In our study, the total pulmonary resistance significantly and sharply increased and remained moderately elevated nine hours after the TIPS procedure. Van der Linden et al 37 reported an acute increase in pulmonary vascular resistance immediately after opening of the shunt and a delayed decrease towards the preshunt values within 30 days of the shunt procedure in patients with alcoholic (n = 13) and non-alcoholic (n = 3) cirrhosis, including six cases with ascites. However, Colombatoet al 38 observed a decrease in pulmonary vascular resistance immediately after the shunt procedure in patients with alcoholic (n = 10) and non-alcoholic (n = 5) cirrhosis, including seven cases with ascites. The inconsistency of the findings in the various studies might be explained by differing underlying cardiac and circulatory states in the cirrhotic patients, dependent on the cause and severity of the liver disease. Whereas diastolic function of the left ventricle has an effect on total pulmonary resistance, systemic vascular resistance is more dependent on the systolic left ventricular function. Therefore, a pre-existing clinically not apparent diastolic dysfunction in a hyperdynamic left ventricle, as in our patients with alcoholic cirrhosis, may explain the opposite reactions of total pulmonary resistance and systemic vascular resistance immediately after TIPS.

In summary, our results indicate that, in our patients with alcoholic cirrhosis, the acute blood volume shift from the splanchnic to the systemic circulation after the TIPS procedure was sufficient to unmask a diastolic dysfunction of the already hyperdynamic left ventricle. In addition, it must be taken into consideration that the TIPS procedure was associated with a further reduction in the already decreased systemic vascular resistance found in portal hypertension. However, all of these acute haemodynamic changes were, to a great extent, compensated for within nine hours of the intervention, and were not of major clinical relevance in our study population.

Altogether, the findings suggests a coexisting clinically not apparent diastolic myocardial dysfunction in our patients with alcoholic cirrhosis, which, at a later stage may be complicated by a concomitant impairment of myocardial contractility, leading to so called “alcoholic cardiomyopathy”.21 In this situation, the TIPS procedure could be complicated by high output congestive heart failure as described in a case study.13 Future studies investigating haemodynamic effects of TIPS procedures in portal hypertension should rigorously define the inclusion criteria for patients in order to categorise the haemodynamic effects of TIPS according to the cause of the cirrhosis (non-alcoholicv alcoholic) and severity of the disease.