Predicting Heart Failure After TIPS: Still More Questions Than Answers
Authors: Anna Baiges, Juan Carlos Garcia‐Pagán
Journal: Hepatology (2019)

See Article on Page 1928 Potential conflict of interest: Dr. Garcia‐Pagán advises Cook Medical and Shionogi. He is on the speakers' bureau for Gore. He received grants from Conatus, Theravance, Novartis, and Exalenz. The transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneous imaging‐guided procedure that effectively reduces portal pressure by diverting blood from the portal to the systemic circulation. Despite being a very effective treatment for portal hypertension–related complications, the use of TIPS was hampered for many years by the high rate of TIPS dysfunction, an issue that has become almost anecdotal since the introduction of covered stents.1 Currently, development of post‐TIPS hepatic encephalopathy and, much less frequently, post‐TIPS liver and cardiac failure, remain as the major complications of TIPS, limiting its use. Until effective preventive and/or therapeutic strategies are available, adequate patient selection is the best existing approach to diminish the rate of these TIPS complications. In this context, we must congratulate the work by Billey et al. published in the current issue of Hepatology,2 evaluating the incidence of post‐TIPS cardiac decompensation and searching for its predictive factors in a large cohort of patients with cirrhosis. TIPS results in large‐volume blood shift from the splanchnic to the systemic circulation, leading to an increase in cardiac output and right heart pressures.3 The abrupt and sudden increase in right heart pressures following TIPS placement is usually transient.3 However, although uncommon, in some patients the development of post‐TIPS cardiac failure can be a complication that is difficult to treat and usually life‐threatening.5 Several previous studies aiming to identify factors predicting post‐TIPS cardiac failure have suggested that patients with functional cardiac alterations,7 globally known as cirrhotic cardiomyopathy (CCM),9 are at highest risk of post‐TIPS cardiac failure. CCM is a condition characterized by an impaired cardiac function with blunted contractile responsiveness to stress, altered diastolic relaxation, and electrophysiological abnormalities in the setting of cirrhosis. By definition, to reach the diagnosis, a preexisting clinically significant structural cardiac disease must be excluded. CCM is usually a silent condition that can be difficult to identify in a stable setting but can become symptomatic under physical or pharmacological stress. Echocardiography, electrocardiography, and some serum biomarkers are the main tools available for its diagnosis. The study by Billey et al. evaluated data from 100 hemodynamically stable patients undergoing TIPS placement for different portal hypertension–related complications (refractory ascites, recurrent variceal bleeding) or prior to abdominal surgery. Before TIPS insertion, patients underwent a thorough cardiac evaluation consisting of electrocardiogram measuring QT interval corrected for the heart rate (QTc), transthoracic echocardiography, right heart catheterization, and brain natriuretic peptide (BNP)/pro‐BNP measurement. Patients were followed up for 1 year, and 20% of them were found to have evolved with severe post‐TIPS cardiac decompensation, requiring admission. Development of severe post‐TIPS cardiac decompensation was not related to the severity of liver disease (no relation with hepatic venous pressure gradient, Child‐Pugh, or Model for End‐Stage Liver Disease scores) or the final portosystemic pressure gradient (PPG). Conversely, a prolonged QTc interval, an elevated pre‐TIPS BNP, elevated E/A and E/e′ ratios, and a left atrial dilatation were all parameters independently associated with post‐TIPS cardiac failure. The study published herein suggests that cut‐off values of less than 40 pg/mL for BNP and less than 125 pg/mL for pro‐BNP could directly rule out the risk of developing post‐TIPS heart failure. For the remaining patients, a transthoracic echocardiogram evaluating left atrial volume index, left ventricular outflow tract, and the E/A and E/e′ indexes could help identify high‐risk patients in whom the adverse effects of TIPS could outweigh its benefits. All previous parameters have been associated with the presence of CCM. However, it is important to note that 28 of the 100 patients included in the study had a previous structural cardiomyopathy. Remarkably, while severe cardiac decompensation occurred in 9 of the 72 (12.5%) patients without previous cardiomyopathy—a prevalence similar to that previously reported—the vast majority of events were concentrated in patients with known structural cardiac disease (11 of 28 patients; 39%). More specifically, post‐TIPS cardiac failure developed in 8 of the 10 (80%) patients with aortic stenosis regardless of its severity (including even those with mild stenosis) and in 3 of the 18 (16.7%) patients with other underlying cardiomyopathies. This finding, as already stated by the authors, reveals the tremendously high risk of severe post‐TIPS cardiac decompensation in patients with aortic stenosis, leading the authors of the study to recommend avoiding TIPS placement in patients with aortic stenosis regardless of the grade. However, even though 2 of the 8 patients with aortic stenosis died, cardiac decompensation was well controlled and clinically managed in the remaining 6 patients: 2 with diuretics and 4 with transcatheter aortic valve implantation. Given the low number of patients included with aortic stenosis and due to the fact that 75% of those developing severe post‐TIPS cardiac decompensation were able to have a good outcome, it is our opinion that the available data are not strong enough to absolutely contraindicate TIPS in patients with asymptomatic aortic stenosis, especially in the acute setting of rescue TIPS where no other therapeutic alternatives exist. The current study also highlights that having an aortic stenosis (not so clear for other valvulopathies or other structural cardiopathies) conveys a risk of post‐TIPS cardiac failure that is much higher than that of the general population of patients with cirrhosis, and therefore these patients should be considered differently. Although the authors attempt to justify that factors predicting post‐TIPS cardiac failure remain the same in the subgroup of patients without aortic stenosis, it must be taken into account that when doing this subanalysis, the number of events was drastically diminished and, consequently, so was the strength of their results. As a good prospective study, the present study has contributed more to raising questions than to giving definitive answers. Indeed, many important issues remain unanswered. Do other valvulopathies, different from aortic stenosis, have the same bad prognosis? As already pointed out by the authors of the manuscript, in patients requiring elective TIPS, should we adopt the strategy of previously treating valvulopathies to improve TIPS outcome? If, despite the low number of patients and events, we accept that the identified factors are indeed accurately predicting severe post‐TIPS cardiac failure in patients without aortic stenosis, are the results of the present study still applicable to all patients undergoing TIPS placement? In that regard, we would like to point out several issues. First, in the studied cohort, refractory ascites was the main indication for TIPS placement, accumulating the higher incidence of cardiac decompensation. It has already been proven that patients with refractory ascites have a higher prevalence of CCM. Would the risk be similar for other TIPS indications? Second, most patients (74%) presented alcohol‐related liver cirrhosis. It is known that alcohol may directly affect cardiac function. Would the results of the study be applicable to other etiologies of cirrhosis? Finally, post‐TIPS PPG of the present cohort was 5 ± 2 mmHg, which is much lower than the recommended cut‐off threshold of 10‐12 mmHg. Could less severe reductions in PPG be associated with a lower incidence of cardiac decompensation? The study by Billey et al. provides a rationale to extend research in this field, encouraging the launch of multicentric studies that would allow for the prospective collection of a large number of patients with very good cardiological characterization. This will permit, among other things, the ability to validate the results of the present study and, if they are reproducible in patients without structural cardiomyopathy, to analyze the potential impact of other valvulopathies in post‐TIPS outcome, the etiology of the liver disease, and less pronounced reductions in PPG.