THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2002 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc. Vol. 97, No. 1, 2002 ISSN 0002-9270/02/$22.00 PII S0002-9270(01)04000-X Modifications of Cardiac Function in Cirrhotic Patients Treated With Transjugular Intrahepatic Portosystemic Shunt (TIPS) Manuela Merli, M.D., Valentina Valeriano, M.D., Stefania Funaro, M.D., Adolfo Francesco Attili, M.D., Andrea Masini, M.D., Cesare Efrati, M.D., Stefano De Castro, M.D., and Oliviero Riggio, M.D. Second Gastroenterology Unit and Cardiology Unit, Department of Clinical Medicine, University of Rome “La Sapienza,” Rome, Italy OBJECTIVES: The implantation of a transjugular intrahepatic portosystemic shunt (TIPS) has been shown to exacerbate the hyperdynamic circulation and might induce a significant cardiac overload. We investigated cardiac function before and 1, 3, 6, and 12 months after the TIPS procedure in cirrhotic patients. METHODS: Eleven patients with nonalcoholic cirrhosis were evaluated. Cardiovascular parameters were assessed by twodimensional Doppler echocardiography. RESULTS: After TIPS, the left ventricular diastolic diameter increased from 26.5 ⫾ 1.8 mm (basal) to 30.0 ⫾ 2.8 mm (6 months) (p ⬍ 0.05), whereas the ejection fraction showed a slight increase (basal, 64.5 ⫾ 3.3; 6 months, 68.1 ⫾ 3.2). The left ventricular pre-ejection period and the isovolumetric relaxation time decreased transiently at 1 month (p ⬍ 0.05). An increased velocity in all of the components of pulmonary venous flow (systolic, diastolic, and atrial) documented the accelerated fluxes induced by the procedure. The estimated pulmonary systolic arterial pressure also increased at 1 month (29.5 ⫾ 1.4 vs 44.1 ⫾ 1.4 mm Hg, p ⬍ 0.05). All of these modifications reverted after 6 months. CONCLUSIONS: Our study demonstrates that nonalcoholic cirrhotic patients, without cardiovascular pathologies, show transient modifications in cardiac dimension and function for 3– 6 months after TIPS caused by the increased volume load shunted to the heart. (Am J Gastroenterol 2002;97: 142–148. © 2002 by Am. Coll. of Gastroenterology) INTRODUCTION In recent years, the transjugular intrahepatic portosystemic shunt (TIPS), a new angiographic technique to achieve portal decompression, has been increasingly applied in patients with liver cirrhosis suffering from complications of portal hypertension (1, 2). It has been reported that the insertion of TIPS could, in the short term, lead to a worsening of the hyperdynamic circulation in cirrhotic patients, which is shown by an acute increase in cardiac output (CO) and decrease in systemic vascular resistance (3–7). Al- though initial observations were that these hemodynamic consequences are mainly confined to the first months (3–5), later studies showed that some of these alterations may persist for a longer period (8). These observations may explain the concern that has been raised by many authors about the possible consequences of TIPS procedure in cardiac function (4, 6 – 8). The occurrence of cardiac complications after TIPS is rather infrequent; however, episodes of acute pulmonary edema, cardiac failure, and myocardial infarction have occasionally been reported (9 –11). Few studies have specifically been performed to evaluate the short and long term modifications in cardiac morphology and function in cirrhotic patients after a TIPS insertion (7, 8). The aim of our study was to investigate the short and long term effects of the TIPS procedure on cardiac performance by using two-dimensional Doppler echocardiography. This technique, being a noninvasive approach, allowed us to perform serial examinations to assess the changes in the morphological and functional cardiac parameters during the first year after TIPS. PATIENTS AND METHODS Patients Eleven consecutive cirrhotic patients (six males and five females, mean age ⫽ 62 ⫾ 3 yr) were investigated. The origin of liver cirrhosis was hepatitis C virus in six patients, hepatitis B virus in two, primary biliary cirrhosis in one, and cryptogenetic in two patients. The severity of liver cirrhosis was classified according to the Child-Pugh classification (12). Two patients were Child-Pugh’s class A, seven were class B, and two were class C. The indication of TIPS was refractory ascites (13) in seven patients and recurrent variceal bleeding (i.e., more than two bleeding events), despite multiple sessions of sclerotherapy, in four. All patients were candidates for an elective TIPS, and the procedure was performed in stable clinical conditions. None of the patients had a history of cardiac and/or lung disease, renal disease, or arterial hypertension. The exclusion of cardiovascular diseases was based on a chest radiography, Cardiac Function After TIPS AJG – January, 2002 electrocardiography, and examination by a cardiologist. In patients with a previous bleeding episode the study was performed in stable hemodynamic conditions a minimum of 7 days after the bleeding had stopped and in the absence of severe anemia (Hb ⬎ 10 g/dl). Spontaneous bacterial peritonitis was always excluded by analysis of ascitic fluid. In patients with refractory ascites the study was performed at least 7 days after the last paracentesis. No patients had a diagnosis of hepatocellular carcinoma. No patients were taking cardioactive drugs, and diuretics were discontinued for at least 5 days before the study commenced. After, TIPS patients were observed according to a standardized protocol that is routinely adopted in our department (14). In brief, this protocol consists of a periodic assessment (after 1, 3, 6, 9, and 12 months) of the patient’s clinical status, liver function, and shunt patency through color Doppler ultrasonography. An upper endoscopy and angiography were routinely performed at 6 months to check the shunt’s function. Angiography was anticipated if shunt malfunction was suspected. This was the case when the flow in the shunt, checked by color Doppler ultrasonography, was reduced more than 25% of the value observed 24 h after the procedure, a change in the direction of the blood flow in the intrahepatic portal branches was detected, and/or esophageal varices or ascites had recurred or worsened. Angioplasty was performed when the portacaval gradient was higher than 12 mm Hg. Protocol All patients were studied prospectively before TIPS procedures and after 1, 3, 6, and 12 months. Echocardiographic examination was performed in the morning after an overnight fast, in a specially equipped quiet room after a 30-min period in the supine position. The heart rate (HR) and arterial pressure were simultaneously recorded, and the mean arterial pressure (MAP) was calculated as diastolic arterial pressure ⫹ 1/3 pulse pressure. The protocol of the study was designed and performed according to the principles of the Declaration of Helsinki. Informed consent was requested and obtained for all patients before they were included in the study. This study is part of a larger project investigating hemodynamic changes after TIPS. Plasma levels of vasoactive substances were not determined in these patients, as that was the aim of a different protocol. Techniques DOPPLER ECHOCARDIOGRAPHY. M-mode and twodimensional echocardiography with spectral and color flow Doppler analysis were performed using an ultrasound machine (Sonos 2500, Hewlett Packard, Andover, MA), with a 2.5- or 3.5-mHz transducer. All patients were examined in the left lateral decubitus position, and the data were obtained during postexpiratory apnea. The images were recorded on a super-VHS videotape and analyzed by two independent observers (15). The echocardiographic data were calculated as the mean values of three measurements of the cardiac 143 cycle. Standard left parasternal long and short axis and apical two-, four-, and five-chamber views were performed in all patients. The following morphological parameters were analyzed: left atrial (LA) and right (RA) diameters, left ventricular end diastolic diameter (LVDD/bs) and left ventricular end systolic diameter (LVSD), right ventricular end diastolic diameter (RVDD), and left ventricular ejection fraction (EF %) calculated using the area-length method. By using the spectral Doppler approach the systolic function was evaluated with the following parameters: pre-ejection period (PEP), which is the interval from the onset of the electrocardiographic QRS to the onset of aortic flow (ms); left ventricular ejection time (LVET), which is the interval from the onset to the cessation of the aortic flow (ms); and their ratio (PEP/LVET). The diastolic function was assessed by analyzing the mitral flow velocity curves: the peak flow velocity in early diastole (E), the peak flow velocity in late diastole (A), and their ratio (E/A); the deceleration time of E wave; and the duration of atrial contraction (ms). The pulmonary venous flow pattern was assessed by analyzing the peak velocity of systolic, diastolic, and atrial component flows. The pulmonary systolic arterial pressure (PSAP) was estimated in patients with tricuspid regurgitation by adding 10 mm Hg to the systolic gradient (4 ⫻ peak velocity2) between the right ventricle and right atrium. Reference values were obtained from 10 healthy subjects (controls) comparable for age and sex (16). The CO, the stroke volume (SV), the cardiac index (CI), and the peripheral vascular resistance (PVR) were calculated by applying the following formulae: CO ⫽ SV ⫻ HR SV ⫽ (left ventricular outflow tract area) ⫻ (mean blood velocity across the aortic valve) ⫻ (ejection time) CI ⫽ CO/BSA (body surface area) PVR ⫽ (MAP ⫻ 80)/CO TIPS PROCEDURE. The TIPS procedure was performed as previously described (1, 14). The stents used were Wallstents (Schneider, Bulach, Switzerland). An antibiotic prophylaxis was performed in all patients before the insertion of TIPS. Anticoagulant therapy with heparin was started immediately after TIPS and was prolonged for the first month for the prophylaxis of early thrombosis. Lactulose was given to all patients for the prevention of hepatic encephalopathy. Statistical Analysis All results were expressed as means ⫾ SDs. Modifications of the echocardiographic parameters at different time intervals, before and after TIPS, were statistically evaluated by analysis of variance and the Newman-Keuls test. p ⬍ 0.05 was considered statistically significant. Values recorded be- 144 Merli et al. AJG – Vol. 97, No. 1, 2002 Table 1. Cardiac Hemodynamic Parameters in Cirrhotic Patients Before and After TIPS MAP (mm Hg) HR (beats/min) CO (L/min) CI (L/min/BSA) PVR (dyne cm⫺5) Before TIPS (n ⫽ 9) Before TIPS (n ⫽ 11) First Month (n ⫽ 9) First Month (n ⫽ 11) Third Month (n ⫽ 9) Sixth Month (n ⫽ 9) 12th Month (n ⫽ 8) 80.9 ⫾ 10.9 76.8 ⫾ 8.7 4.4 ⫾ 0.8 2.7 ⫾ 0.5 1508 ⫾ 387 79.8 ⫾ 10.1 76.1 ⫾ 8.7 4.2 ⫾ 0.9 2.5 ⫾ 0.6 1587 ⫾ 403 84.3 ⫾ 7.3 73.1 ⫾ 7.2 5.6 ⫾ 1.3 3.4 ⫾ 0.9 1281 ⫾ 421 82.6 ⫾ 7.7 73.1 ⫾ 7.2 5.6 ⫾ 1.2 3.3 ⫾ 0.8 1247 ⫾ 384 82.8 ⫾ 10 79.2 ⫾ 8.0 5.04 ⫾ 1.08 3.02 ⫾ 0.7 1393 ⫾ 427 83.5 ⫾ 11 76.2 ⫾ 8.4 4.7 ⫾ 0.9 2.8 ⫾ 0.7 1496 ⫾ 474 88.5 ⫾ 1.6 75.2 ⫾ 4.8 4.6 ⫾ 0.8 2.7 ⫾ 0.61 1587 ⫾ 321 BSA ⫽ body surface area. fore TIPS were also compared to reference values obtained in healthy controls using the Student’s t test for unpaired data. RESULTS nine patients who completed an adequate follow-up were evaluated separately (Tables 1 and 2). One of these patients died of hepatorenal syndrome at 11 months. None of the patients showed clinical evidence of cardiac failure during the follow-up. Clinical Results The insertion of TIPS induced a mean reduction of the portocaval gradient from 20.3 ⫾ 1.8 to 8.4 ⫾ 0.6 mm Hg. The patients treated for refractory ascites showed an improvement after TIPS with disappearance of ascites or a significant reduction in the dose of diuretics administered. Mild ascites was still present in three patients at 6 months and in one at 12 months. No episodes of recurrent bleeding from esophageal varices were recorded. Four patients developed new episodes of hepatic encephalopathy after TIPS. All of the episodes occurred within the first 3 months and were successfully treated with oral lactulose. Shunt stenosis was suspected in two patients after 3 and 6 months of follow-up, respectively. The first patient refused to undergo further angiography; the second patient had evidence of severe shunt stenosis at angiography, but angioplasty could not be performed because of complications. The ecocardiographic parameters of these two patients were considered only in the analysis of the differences between basal state and 1 month after TIPS. The data of the Hemodynamic and Cardiac Function Hemodynamic parameters before TIPS procedure and during follow-up are reported in Table 1. MAP and HR were not significantly modified after TIPS. One month after TIPS placement CO was 28% increased, CI was 28% increased, and PVR was 18% decreased versus basal values. These parameters gradually returned to levels similar to pre-TIPS values after 3– 6 months. Before TIPS, LA diameter and RVDD were significantly increased in cirrhotic patients relative to healthy controls (LA diameter, 39.3 ⫾ 2.8 vs 30.4 ⫾ 4.5 mm; p ⬍ 0.001; RVDD, 30.4 ⫾ 4.5 vs 22.1 ⫾ 6.0 mm, p ⬍ 0.001). RA diameter values were within the upper limit of normal range (Table 2). A significant increase in LVDD/bs was observed at 1, 3, and 6 months after TIPS (Fig. 1). This parameter returned to baseline levels at 12 months. LVSD (Fig. 1) did not change after the procedure, whereas the EF showed a slight but nonsignificant increase. Before TIPS, flow velocities and systolic time intervals, Table 2. Cardiac Morphology and Function in Cirrhotic Patients Before and After TIPS LVDD/bs (mm/m2) LVSD (mm) RVDD (mm) LA (mm) RA (mm) EF (%) E (cm/s) A (cm/s) E/A IVRT (ms) PEP (ms) LVET (ms) PEP/LVET (ms) PSAP (mm Hg) Before TIPS (n ⫽ 9) Before TIPS (n ⫽ 11) First Month (n ⫽ 9) First Month (n ⫽ 11) Third Month (n ⫽ 9) Sixth Month (n ⫽ 9) 12th Month (n ⫽ 8) 26.3 ⫾ 1.9 25.1 ⫾ 2.8 30.3 ⫾ 5† 39 ⫾ 2.9† 40.2 ⫾ 6.5 64.6 ⫾ 3.7 57.5 ⫾ 9.6 61.9 ⫾ 13.6 0.95 ⫾ 0.2 127.6 ⫾ 21.4 82.1 ⫾ 14† 295.2 ⫾ 18.7 0.28 ⫾ 0.05 29.1 ⫾ 4.1 26.5 ⫾ 1.8 24.9 ⫾ 2.5 30.4 ⫾ 4.5† 39.3 ⫾ 2.8† 41 ⫾ 6.1 64.5 ⫾ 3.3 58.8 ⫾ 9.4 61.7 ⫾ 12.2 0.35 ⫾ 0.35 135 ⫾ 27.1 84.5 ⫾ 14.1† 301.4 ⫾ 25.4 0.27 ⫾ 0.01 29.5 ⫾ 3.7 31.5 ⫾ 1.6* 24.8 ⫾ 1.9 30.2 ⫾ 3.5 41.1 ⫾ 3.1 42.8 ⫾ 5.1 66.2 ⫾ 5.1 76.6 ⫾ 14* 70.3 ⫾ 14.5 1.15 ⫾ 0.3 106.3 ⫾ 17.4 65.4 ⫾ 10.7 306.6 ⫾ 33.5 0.20 ⫾ 0.03 43.7 ⫾ 5.0* 31.3 ⫾ 2.1* 25.1 ⫾ 2.4 29.7 ⫾ 3.4 40.8 ⫾ 3.3 42.8 ⫾ 4.6 65.7 ⫾ 5 76.9 ⫾ 14* 69.3 ⫾ 14.3 0.49 ⫾ 0.56 107 ⫾ 15.7 64 ⫾ 10.6* 304 ⫾ 34 0.20 ⫾ 0.00 44.1 ⫾ 4.6* 30.0 ⫾ 3.1* 27.5 ⫾ 4.5 30.1 ⫾ 4.4 42.5 ⫾ 3 42.7 ⫾ 4.4 68.2 ⫾ 2.8 66.4 ⫾ 13.4 70.7 ⫾ 13.8 0.94 ⫾ 0.2 102 ⫾ 26.5* 68.1 ⫾ 11.3 298.6 ⫾ 30.8 0.24 ⫾ 0.05 30.9 ⫾ 2.1 30.0 ⫾ 2.8* 25.6 ⫾ 4.0 28.5 ⫾ 3.8 40.6 ⫾ 2.6 41.5 ⫾ 3.4 68.1 ⫾ 3.2 66.3 ⫾ 12.1 68.6 ⫾ 15.8 0.99 ⫾ 0.27 111.1 ⫾ 28.1 75.3 ⫾ 18.2 296.4 ⫾ 23.9 0.24 ⫾ 0.05 31.1 ⫾ 5.1 28.0 ⫾ 1.6 26.2 ⫾ 4.8 28.9 ⫾ 4.2 40.5 ⫾ 2.8 43.1 ⫾ 3.0 66.0 ⫾ 3.5 62.9 ⫾ 12.9 69.5 ⫾ 13.6 0.93 ⫾ 0.4 120.8 ⫾ 21.7 70.5 ⫾ 18.6 288.3 ⫾ 9.8 0.24 ⫾ 0.06 29.7 ⫾ 4.3 A ⫽ peak flow velocity in late diastole; E ⫽ peak flow velocity in early diastole; IVRT ⫽ isovolumetric relaxation time. * p ⬍ 0.05 vs basal values in the same group. † p ⬍ 0.001 vs healthy controls. Cardiac Function After TIPS AJG – January, 2002 145 Figure 2. Modifications of isovolumetric relaxation time and PEP in nine patients before and after TIPS. *p ⬍ 0.05 vs basal. Figure 1. Modifications of LVDD/bs and LVSD in nine patients before and after TIPS. *p ⬍ 0.05 vs basal. analyzed by the Doppler approach, were substantially normal in cirrhotic patients, with the exception of the PEP, which was significantly shorter (84.5 ⫾ 14.1 ms) than in healthy controls (99.3 ⫾ 5.4 ms, p ⬍ 0.005). The TIPS procedure caused a further decrease of PEP at 1 month (p ⬍ 0.05). This parameter tended to return to baseline values thereafter (Fig. 2). The PEP/LVET ratio was normal before TIPS and showed minor, nonsignificant changes after TIPS. Regarding the indices of diastolic function, the E wave velocity of the mitral flow increased significantly at 1 month (p ⬍ 0.05). However, because of a parallel but nonsignificant increase in the A component, the E/A ratio did not show significant changes. Also, the E wave, the deceleration time of E wave, and the duration of atrial contraction did not change after TIPS. A reduction in the isovolumetric relaxation time was observed at 1 month (135 ⫾ 27.1 vs 107 ⫾ 15.7 ms, basal vs 1 month, respectively) and reached statistical significance at 3 months (102 ⫾ 26.5, p ⬍ 0.05) (Fig. 2). Pulmonary vein flow analysis showed a significant increase in the velocity of the three components (systolic, diastolic, and atrial) 1–3 months after TIPS (Fig. 3). The estimated values of PSAP were 29.5 ⫾ 3.7 mm Hg in the basal state and increased to 44.1 ⫾ 4.6 mm Hg 1 month after TIPS (p ⬍ 0.05), documenting a transient pulmonary hypertension. These changes showed a progressive normalization from 3 months after TIPS (Fig. 3). DISCUSSION A worsening of the hemodynamic alterations already present in cirrhotic patients has been reported when a portosystemic shunt is artificially created (3, 4, 6). In fact, the creation of a portosystemic shunt abruptly causes a further increase in the amount of blood volume that returns to the right atrium from the splanchnic area. In this case, if the cardiac reserve is reduced, a latent cardiomyopathy can be unmasked and clinical signs of heart failure may become apparent (9). 146 Merli et al. Figure 3. Modifications of transpulmonary systolic peak flow velocity (S, 䊐), transpulmonary diastolic peak flow velocity (D, ●), transpulmonary reverse peak flow velocity (A, ‚), and PSAP in nine patients before and after TIPS. *p ⬍ 0.05 vs basal. To evaluate if the hemodynamic changes induced by TIPS insertion may influence cardiac morphology and function, we performed serial Doppler echocardiography examinations in a group of nonalcoholic cirrhotic patients before and after TIPS implantation. Doppler echocardiography not only allows one to obtain both anatomical and functional information but is also a widely available, safe, inexpensive imaging modality. Moreover, a good relationship between echocardiography and more invasive techniques such as thermodilution, for the assessment of CO and PVR in cirrhotic patients, has been reported (7, 17). Our study shows that the insertion of TIPS causes modifications to cardiac morphology and function that can be clearly shown by echocardiography. Before TIPS, the main alterations presented in cirrhotic patients were a significant enlargement of the LA diameter and RVDD and a reduction in the left ventricular PEP. AJG – Vol. 97, No. 1, 2002 Similar findings have been previously reported in cirrhosis of various etiologies (16, 18 –22). The main changes we observed were those that occurred 1 month after TIPS implantation. At this time, although RA and LA diameters were unchanged versus pre-TIPS values, we observed a significant increase of the LVDD/bs that persisted around the 3- and 6-month marks and declined at 12 months. The increment of the end diastolic diameter of the left ventricle can be explained by the enhanced filling due to the greater amount of blood drained to the heart by the new shunt (23). An adequate adaptation of the left ventricular function can be suggested by the unchanged LVSD, which shows an adequate systolic emptying and a slight though statistically nonsignificant increment of the EF (Table 2). The adaptation to the increased cardiac and central vascular volume could also be suggested by the modifications of some Doppler parameters observed after TIPS. The PEP, which is the time between the closure of the atrioventricular valve and the opening of the aortic valve, showed a significant decrease after 1 month. This decrease may suggest a good cardiac contractility of the left ventricle, which is able to adapt to the increased central volume by accelerating this phase of the cardiac cycle. The concomitant reduction of the isovolumetric relaxation time (Fig. 2) seems to confirm the above explanation. Although a transient rise in the early component of the transmitral flow (E) was observed 1 month after TIPS, the E/A ratio, which was similar to that of controls at baseline, did not show significant changes during the follow-up. The E/A ratio has been considered a marker of diastolic function (24), and recent reports have indicated that it may be altered in cirrhotic patients (22). In a previous study we found that alteration in the E/A ratio was more typical of cirrhotics with tense ascites (16). In any case, the lack of modification of this parameter may once again suggest a good adaptation of cardiac function. In fact, not only the systolic function, but also the diastolic function, which is an early marker of cardiac impairment, seemed to be maintained. From our results, no reduction in cardiac performance occurred after the TIPS procedure. It should also be noted that our cohort’s patients’ diseases were not of alcoholic origin, and this may explain why alterations in the left ventricular diastolic or systolic functions were absent in the cardiac assessment of our patients (in the basal state), at variance with previous reports (18, 19, 25). Even the E/A ratio, which is an early index of diastolic dysfunction, was not altered in our patients before TIPS. An increase in all of the components of the pulmonary flow velocities (systolic, diastolic, atrial) was detected during the first month. A similar time course and pattern were observed for the estimated PSAP (Fig. 3). The occurrence of a transient pulmonary hypertension 1 month after TIPS implantation has already been described (7, 26), even if its mechanism is still unclear. Either a rise in CO or the effect of neuroumoral mediators with vasoconstrictor action on the Cardiac Function After TIPS AJG – January, 2002 pulmonary circulation may contribute to this phenomena. A high concentration of vasoconstrictor substances after TIPS could be due to a reduced hepatic clearance or increased secretion due to various stimuli associated with TIPS placement such as the damage of liver parenchyma by portal vein puncture, dilation of the intraparenchymal tract, and insertion of the metallic stent (26). This latter theory can explain the slow normalization of PSAP (time needed to repair) reported in this article, together with an adaptation of the heart to the new hemodynamic state. In summary, our data suggest that cirrhotic patients show changes of diastolic left ventricular dimensions and transvalvular flow velocities after TIPS implantation. These modifications are caused by an adaptation of the cardiac muscle to the increased cardiac preload that occurs after the procedure. The increase in central blood volume that is efficiently handled by the heart can also justify the marked elevation in Doppler flow velocities measured at different cardiac sites. These changes were confined to the first 6 months and all parameters tended to normalize within the first year, probably because of the stabilization of the new hemodynamic state. The time course of these changes is similar to what has been reported in other studies (8). Therefore, although an accurate assessment of cardiac function before TIPS is recommended, our study demonstrated that cirrhotic patients without evidence of cardiovascular pathologies are able to incrementally increase cardiac contractility to compensate for the increased volume load shunted to the heart after TIPS insertion. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. ACKNOWLEDGMENT 15. Supported by grant 99051501 146 from Finanziamento progetti di ricerca scientifica della Facoltà di Medicina e Chirurgia dell’Università di Roma “La Sapienza.” 16. Reprint requests and correspondence: Manuela Merli, M.D., II Gastroenterologia, Dipartimento di Medicina Clinica, Viale dell’Università 37, 00185 Roma, Italy. Received Jan. 15, 2001; accepted June 13, 2001. 17. 18. REFERENCES 1. Roessle M, Haag K, Ochs A, et al. The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding. N Engl J Med 1994;330:165–71. 2. Shiffman ML, Jeffers L, Hoofnagle JH, Tralka TS. The role of transjugular intrahepatic portosystemic shunt for treatment of portal hypertension and its complications: A conference sponsored by the National Digestive Diseases Advisory Board. Hepatology 1995;22:1591–7. 3. Azoulay D, Castaing D, Dennison A, et al. Transjugular intrahepatic portosystemic shunt worsen the hyperdynamic circulatory state of the cirrhotic patient: Preliminary report of a prospective study. Hepatology 1994;19:129 –32. 4. Rodriguez-Laiz JM, Banares R, Echenagusia A, et al. Effects of transjugular intrahepatic portosystemic stent-shunt (TIPS) on splanchnic and systemic hemodynamics and hepatic func- 19. 20. 21. 22. 23. 147 tion in patients with portal hypertension. Preliminary results. Dig Dis Sci 1995;40:2121–7. Quiroga J, Sangro B, Nunez M, et al. Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: Effect on clinical, renal, humoral and hemodynamic parameters. Hepatology 1995;21:986 –94. Colombato LA, Spahr L, Martinet JP, et al. Haemodynamic adaptation two months after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients. Gut 1996;39: 600 – 4. Huonker M, Schumacher YO, Ochs A, et al. Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic shunt. Gut 1999;44: 743– 8. Lotterer E, Wengert A, Fleig WE. Transjugular intrahepatic portosystemic shunt: Short-term and long-term effects on hepatic and systemic hemodynamics in patients with cirrhosis. Hepatology 1999;29:632–9. Braverman AC, Steiner MA, Picus D, White H. High output congestive heart failure following transjugular intrahepatic portal-systemic shunting. Chest 1995;107:1467–9. Hadengue A, Moreau R, Sogni P, et al. Risk of adverse hemodynamic effects after intrahepatic shunts (TIPS): Preliminary results. Hepatology 1992;16:241A. Helton WS, Belshaw A, Althaus S, et al. Critical appraisal of the angiographic portacaval shunt (TIPS). Am J Surg 1993;5: 566 –71. Pugh RNH, Murray-Lion IM, Dawson JL. Transection of oesophagus for bleeding oesophagus varices. Br J Surg 1973; 60:646 –9. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996;23:164 –76. Merli M, Salerno F, Riggio O, et al. Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: A randomised controlled trial. Hepatology 1998;27:40 –5. Henry VL, De Maria A, Gramiak R, et al. Report of the American Society of Echocardiography: Nomenclature and standards in two dimensional echocardiography. Circulation 1980;62:212–7. Valeriano V, Funaro S, Lionetti R, et al. Modification of cardiac function in cirrhotic patients with and without ascites. Am J Gastroenterol 2000;95:3200 –7. Rector WG, Hossack KF. Pathogenesis of sodium retention complicating cirrhosis: Is there room for diminished “effective” arterial blood volume? Gastroenterology 1988;95:1658 – 63. Finucci G, Desideri A, Sacerdoti D, et al. Left ventricular diastolic function in liver cirrhosis. Scand J Gastroenterol 1996;31:279 – 84. Askanas A, Udoshi M, Sadjadi SA. The heart in chronic alcoholism: A non-invasive study. Am Heart J 1980;99:9 –16. Keller H, Bezjak V, Stegaru B, et al. Ventricular function in cirrhosis and portosystemic shunt: A two-dimensional echocardiographic study. Hepatology 1988;8:658 – 62. Rector WG Jr, Adair O, Hossack KF, Rainguet S. Atrial volume in cirrhosis: Relationship to blood volume and plasma concentration of atrial natriuretic factor. Gastroenterology 1990;99:766 –70. Pozzi M, Carugo S, Boari G, et al. Evidence of functional and structural cardiac abnormalities in cirrhotic patients with and without ascites. Hepatology 1997;26:1131–7. Wong WW, Liu P, Blendis L, Wong F. Long-term renal sodium handling in patients with cirrhosis treated with transjugular intrahepatic portosystemic shunts for refractory ascites. Am J Med 1999;106:315–22. 148 Merli et al. 24. Nishimura RA, Housmans PR, Hatle LK, Tajik AJ. Assessment of diastolic function of the heart: Background and current applications of Doppler echocardiography. Physiologic and pathophysiologic features. Mayo Clin Proc 1989;64:71– 81. 25. Kelbaek H, Eriksen J, Brynjolf I, et al. Cardiac performance in AJG – Vol. 97, No. 1, 2002 patients with asymptomatic alcoholic cirrhosis of the liver. Am J Cardiol 1984;54:852–5. 26. Van der Linden P, Le Moine O, Ghysels M, et al. Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: Effects on right ventricular function. Hepatology 1996; 23:982–7.