Hemodynamic Changes Following the Transjugular Intrahepatic Portosystemic Shunt

Chapter 16: Hemodynamic Changes Following the Transjugular Intrahepatic Portosystemic Shunt

Deddeh Ballah and Timothy W.I. Clark

Introduction

Transjugular intrahepatic portosystemic shunt (TIPS) has become the standard of care for portal decompression for the treatment of complications of portal hypertension (PHT), including bleeding varices and diuretic-resistant ascites. The hemodynamic changes associated with TIPS creation are complex and affect the portomesenteric venous and arterial systems as well as the heart. This chapter focuses on the hemodynamic changes that occur after TIPS and their clinical significance.

Hemodynamics of Cirrhosis and Portal Hypertension in Brief

The hemodynamic changes caused by cirrhosis and PHTs result from a complex interplay of neuorhormonal and structural changes. Cirrhosis creates increased resistance to portal blood flow, inducing portal venous dilatation and congestion of portal venous flow. The increased resistance to portal blood flow leads to the development of portosystemic collaterals. Ultimately, there is an increase in portal venous inflow, creating a hyperdynamic circulation that maintains and exacerbates PHT.1,2

The intrahepatic resistance caused by cirrhosis has both static and dynamic components. Hepatic stellate cells can cause sinusoidal vasoconstriction via contractile cytoplasmic processes through paracrine effects of endothelin-1 (ET-1) and relaxation via interactions with sinusoidal endothelial and paracrine effects of nitrous oxide (NO). The quantity of hepatic stellate cells increases in cirrhosis and induces sinusoidal vasoconstriction with increased vascular resistance. Although there is decreased hepatic NO production, there is increased systemic and splanchnic NO production, causing decreased systemic vascular resistance (SVR).¹ This causes a decrease in central blood volume.³ The systemic circulation attempts to compensate for the decrease in effective arterial blood volume by sympathetic activation, activation of the renin–angiotensin–aldosterone-system (RAAS), and an increase in antidiuretic hormone.¹ In response to the decreased SVR, cardiac output increases, producing a higher than normal cardiac index.³ Chronic increases in flow with vasodilatation causes endothelial signaling that leads to chronic increase in vessel diameter.³ Eventually, individuals experience cardiac insufficiency and are unable to maintain arterial pressure as vasodilatation progresses. The kidneys become underperfused, and patients go into renal failure.³

Similar to systemic circulation, the liver is equipped with an intrinsic mechanism to compensate for decreased total hepatic blood flow. When portal blood flow is decreased to the liver, the hepatic arterial buffer response (HABR) maintains hepatic perfusion by increasing hepatic artery flow. Cirrhotic patients have been observed via duplex Doppler ultrasound examination to have hepatofugal portal venous blood. Patients with hepatofugal portal venous blood flow have a statistically significant lower resistive index in their hepatic arteries compared with patients with hepatopedal flow indicating an active HABR. Interestingly, resistive index does not correlate inversely with the portosystemic gradient. Patients with hepatofugal flow elicit the HABR, which is accompanied by a decrease in the resistive index of the hepatic artery.⁴

Intrahepatic Hemodynamic Changes After TIPS

TIPS is a high-volume conduit connecting the portal and caval systems that causes acute portal decompression.² This low-resistance portal outflow tract allows for an increase in portal blood flow^2,5 and portal vein (PV) diameter.⁵ Low-dose galactose clearance and Doppler ultrasonography have been used to note the increase in portal venous flow to be 48% after TIPS placement. After TIPS placement, the velocities in the main PV increase up to 170%^2,5,6 and remain increased after shunt placement for at least up to 12 months.⁶ After TIPS placement, velocity through shunts is high velocity. Although peak velocities through shunts decrease slightly over time, they remain higher than pre-TIPS velocities.⁶ The low-resistance shunt also results in diversion of flow toward the shunt and away from the liver. Doppler ultrasonography demonstrates flow reversal in the right and left hepatic veins from hepatopedal flow to hepatofugal after TIPS insertion.⁶ This is consistent with the finding that low-dose galactose clearance after TIPS demonstrates a 48% increase in portal blood flow but a 60% decrease in effective hepatic blood flow within 4 to 6 days after shunt. Color-flow Doppler measures that portal flow proximal to the TIPS increased with shunting. The increased portal flow is diverted through the stent and away from the hepatic parenchyma.² Rosemurgy et al point out that most portal flow after the TIPS is non-nutrient because it is preferentially shunted to the systemic venous system and does not supply the liver.² Dynamic computed tomography has been used to measure changes in perfusion of the liver parenchyma. Compared with control participants, patients with cirrhosis showed increased arterial hepatic perfusion, decreased portal blood hepatic perfusion, and decreased total hepatic perfusion. Post-TIPS measurements revealed a significant increase in arterial blood hepatic perfusion and total hepatic perfusion, but portal venous hepatic perfusion remained the same.⁷ In contrast to other studies, liver scintigraphy evaluation after hepatic perfusion has shown portal venous blood flow velocity increased significantly as well as the contribution from portal venous blood flow for hepatic perfusion increased from 9.2% to 38.2%.⁸

TIPS creation does not only affect flow through the PVs but also affects flow through the hepatic arteries. Doppler ultrasound interrogation has found hepatofugal and hepatopedal portal venous flow in patients with cirrhosis. Gulberg et al³ noted that the hepatic artery resistive index was lower in patients with hepatofugal flow compared with those with hepatopedal flow before TIPS. After TIPS creation, the hepatic artery resistive index decreased in patients with hepatopedal flow but did not change in patients with hepatofugal flow. Because TIPS creation in patients with hepatofugal flow does not cause a further decrease in the amount of hepatic blood supply originating from the PV, there is no further hepatic artery dilatation.4 Twenty-four hours after TIPS placement, there is a statistically significant increase in hepatic artery peak systolic velocity (HAPSV). This increase in hepatic artery flow reflects the HABR because TIPS results in decreased portal venous flow delivered to the liver. The HAPSV decreases during 12-month follow-up but remains elevated above baseline.⁶ Similarly, Patel et al⁹ used Doppler ultrasonography to investigate hepatic arterial blood flow after TIPS. They found an increase in hepatic arterial peak systolic velocity and hepatic arterial blood flow after TIPS. Hepatic artery diameter did not change significantly after TIPS. There was no correlation between the change in average increase in hepatic arterial blood flow before and after TIPS and the change in portosystemic gradient before and after TIPS.⁹ It is interesting to note that TIPS placement causes similar portosystemic gradient reductions in patients with cirrhosis with hepatofugal portal venous flow compared with those with hepatopedal portal venous flow.⁴

Direct measurements of hepatic artery blood flow with intravascular Doppler sonography to investigate real-time changes in velocity during TIPS insertion reveal the same results as studies using indirect measurement methods. As seen in other studies, the average arterial peak velocity and maximum arterial peak velocities increased significantly after TIPS. Balloon occlusion of the shunt has been performed to determine the reversibility of average arterial peak velocity. Balloon occlusion resulted in restoration of the arterial average peak velocity not only to pre-TIPS velocity, but it also decreased to below baseline. Deflation of the balloon resulted in an increase of average peak velocity to post-TIPS values.¹⁰

Itkin et al investigated a new method for direct measurement of intrahepatic blood flow.¹¹ Their study validated and optimized the use of a thermodilutional catheter with the ability to measure retrograde blood flow in a domestic swine model. The authors demonstrated a high correlation between portal venous flow measurements taken with a thermodilutional catheter versus a gold standard of a surgically placed perivascular Doppler probe (r² = 0.96; P <0.001). Thermodilutional catheter blood flow rates of the PV and hepatic artery were measured before TIPS and 2 weeks after TIPS. In the swine with greater blood flow in the TIPS compared with the PV, an arteriogram was performed and demonstrated filling of the left and right PV with hepatofugal flow toward the proximal end of the TIPS. An occlusion balloon inflated at the common origin of the hepatic artery demonstrated decreased flow through the TIPS. When the balloon was completely deflated, flow returned to baseline. Similar to the study by Radeleff et al, the significant increase in blood flow after TIPS has been demonstrated to be secondary to increased hepatic artery blood flow. This experiment demonstrated arterioportal shunting both angiographically and hemodynamically.¹¹

A prospective clinical study quantified hepatic artery-to-PV shunting using a direct thermodilutional catheter-based technique and by measuring changes in blood oxygenation within the TIPS and PV in patients undergoing primary TIPS insertion or revision ( Fig. 16.1). The study quantified shunting assuming that flow in the TIPS (Q_TIPS) was the combination of main PV flow (Q_portal) plus the reversed intrahepatic portal flow from hepatic artery-to-portal shunting; that is, Q_TIPS = Q_portal + reversed flow. There was a 64% increase in mean portal flow after TIPS. Mean Q_TIPS was a 44% increase from final Q_portal ( Fig. 16.2).

Fig. 16.1 Completion transjugular intrahepatic portosystemic shunt (TIPS) portogram showing the location of thermodilutional catheter during flow measurements in a patient with hepatitis C and alcoholic cirrhosis. Initial portosystemic gradient was 22 mm Hg; the final gradient was 8 mm Hg. Note the TIPS flow is higher than the main portal vein flow. Reprinted with permission from Itkin M, Trerotola SO, Stavropoulos SW, et al. Portal flow and arterioportal shunting after transjugular intrahepatic portosystemic shunt creation. J Vasc Interv Radiol 2006;17(1):55–62.

Given that only three of 26 patients had imaging evidence of an umbilical vein, it is highly unlikely that flow within a recanalized paraumbilical vein increased flow in the TIPS. This group hypothesized that shunting from the hepatic arterial system at the sinusoidal or presinusoidal level into the right and left PVs with hepatofugal flow into the TIPS. If arterioportal shunting occurs at the transvasal level, oxygen tension in the TIPS will be higher than in the PV. Conversely, if arterioportal shunting occurs via sinusoids where the efficient oxygen exchange of the periportal triad occurs, the oxygen tension will be lower in TIPS. Because there was only a small reduction in oxygen saturation when comparing the TIPS with the PV shunting, the study concluded that shunting occurs at the level of the sinusoid.12