Abstract
Background
Liver dysfunction is associated with an increased risk of mortality after cardiac interventions. The Fibrosis-4 (FIB-4 index), a marker of hepatic fibrosis, has been associated with a worse prognosis in heart failure. The prognostic relevance of the index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. The aim of this study was to evaluate the clinical implications associated with the FIB-4 index in patients undergoing TAVR.
Methods
Between May 2012 and June 2019, 941 patients undergoing TAVR were stratified into a low or high FIB-4 index group, based on a cutoff value that was determined according to a receiver operating characteristic curve predicting 1-year all-cause mortality.
Results
Patients with a high FIB-4 index (n = 480), based on the cutoff value of 1.82, showed higher rates of pulmonary hypertension (43.8% vs. 31.8%, p < 0.01), right-ventricular systolic dysfunction (29.5% vs. 19.2%, p < 0.01) and larger inferior vena cava diameter (1.6 ± 0.6 cm vs. 1.3 ± 0.6 cm, p < 0.01) than patients with a low FIB-4 index (n = 461). Furthermore, a high FIB-4 index was associated with a significantly higher cumulative 1-year all-cause mortality (17.5% vs. 10.2%, p < 0.01) and non-cardiovascular mortality (12.1% vs. 2.5%, p < 0.01), compared to a low FIB-4 index. Multivariable analysis revealed that a high FIB-4 index was independently associated with all-cause mortality (HR: 1.75 [95% CI: 1.18–2.59], p < 0.01).
Conclusions
A high FIB-4 index is associated with right-sided heart overload and an increased risk of mortality in patients undergoing TAVR. The FIB-4 index may be useful as an additional predictor of outcomes in these patients.
Graphical abstract
Similar content being viewed by others
References
Mack MJ, Leon MB, Smith CR et al (2015) 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 385(9986):2477–2484. https://doi.org/10.1016/S0140-6736(15)60308-7
Mack MJ, Leon MB, Thourani VH et al (2019) Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 380(18):1695–1705. https://doi.org/10.1056/NEJMoa1814052
Araujo L, Dombrovskiy V, Kamran W et al (2017) The effect of preoperative liver dysfunction on cardiac surgery outcomes. J Cardiothorac Surg 12(1):73. https://doi.org/10.1186/s13019-017-0636-y
Sterling RK, Lissen E, Clumeck N et al (2006) Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43(6):1317–1325. https://doi.org/10.1002/hep.21178
Park HJ, Park JY, Jung SM et al (2019) Fibrosis-4 index at diagnosis is associated with all-cause mortality in patients with microscopic polyangiitis and granulomatosis with polyangiitis. BMC Gastroenterol 19(1):90. https://doi.org/10.1186/s12876-019-1007-z
Kim M, Jun DW, Park H, Kang BK, Sumida Y (2020) Sequential combination of FIB-4 followed by M2BPGi enhanced diagnostic performance for advanced hepatic fibrosis in an average risk population. J Clin Med. https://doi.org/10.3390/jcm9041119
Maeda D, Sakane K, Ito T et al (2020) Fibrosis-4 index reflects right-sided filling pressure in patients with heart failure. Heart Vessel 35(3):376–383. https://doi.org/10.1007/s00380-019-01505-y
Saito Y, Okumura Y, Nagashima K et al (2020) Impact of the Fibrosis-4 index on risk stratification of cardiovascular events and mortality in patients with atrial fibrillation: findings from a Japanese multicenter registry. J Clin Med. https://doi.org/10.3390/jcm9020584
Sinning JM, Werner N, Nickenig G, Grube E (2012) Next-generation transcatheter heart valves: current trials in Europe and the USA. Methodist Debakey Cardiovasc J 8(2):9–12. https://doi.org/10.3390/jcm9020584
Nishimura RA, Otto CM, Bonow RO et al (2017) 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. J Am Coll Cardiol 70(2):252–289. https://doi.org/10.1016/j.jacc.2017.03.011
Baumgartner H, Falk V, Bax JJ et al (2017) 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 38(36):2739–2791. https://doi.org/10.1093/eurheartj/ehx391
Ponikowski P, Voors AA, Anker SD et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200. https://doi.org/10.1093/eurheartj/ehw128
Sawada N, Kawata T, Daimon M et al (2019) Detection of pulmonary hypertension with systolic pressure estimated by doppler echocardiography. Int Heart J 60(4):836–844. https://doi.org/10.1536/ihj.18-453
Kappetein AP, Head SJ, Genereux P et al (2012) Updated standardized endpoint definitions for transcatheter aortic valve implantation: the valve academic research consortium-2 consensus document. J Am Coll Cardiol 60(15):1438–1454. https://doi.org/10.1016/j.jacc.2012.09.001
Compagnone M, Moretti C, Marcelli C et al (2019) Surgical risk scores applied to transcatheter aortic valve implantation: friends or foes? short-term and long-term outcomes from a single-center registry. J Invasive Cardiol 31(10):E282–E288
Nakashima M, Sakuragi S, Miyoshi T et al (2021) Fibrosis-4 index reflects right ventricular function and prognosis in heart failure with preserved ejection fraction. ESC Heart Fail 8(3):2240–2247. https://doi.org/10.1002/ehf2.13317
Alushi B, Beckhoff F, Leistner D et al (2019) Pulmonary hypertension in patients with severe aortic stenosis: prognostic impact after transcatheter aortic valve replacement: pulmonary hypertension in patients undergoing TAVR. JACC Cardiovasc Imaging 12(4):591–601. https://doi.org/10.1016/j.jcmg.2018.02.015
Sannino A, Gargiulo G, Schiattarella GG et al (2014) Increased mortality after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and low ejection fraction: a meta-analysis of 6898 patients. Int J Cardiol 176(1):32–39. https://doi.org/10.1016/j.ijcard.2014.06.017
Yamamoto M, Hayashida K, Mouillet G et al (2013) Prognostic value of chronic kidney disease after transcatheter aortic valve implantation. J Am Coll Cardiol 62(10):869–877. https://doi.org/10.1016/j.jacc.2013.04.057
Witberg G, Codner P, Landes U et al (2021) Effect of transcatheter aortic valve replacement on concomitant mitral regurgitation and its impact on mortality. JACC Cardiovasc Interv 14(11):1181–1192. https://doi.org/10.1016/j.jcin.2021.02.030
Shamekhi J, Sugiura A, Tabata N et al (2020) Impact of tricuspid regurgitation in patients undergoing transcatheter aortic valve replacement. JACC Cardiovasc Interv 13(9):1135–1137. https://doi.org/10.1016/j.jcin.2019.09.045
McPherson S, Hardy T, Dufour JF et al (2017) Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol 112(5):740–751. https://doi.org/10.1038/ajg.2016.453
Wai CT, Greenson JK, Fontana RJ et al (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38(2):518–526. https://doi.org/10.1053/jhep.2003.50346
Angulo P, Hui JM, Marchesini G et al (2007) The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 45(4):846–854. https://doi.org/10.1002/hep.21496
Xanthopoulos A, Starling RC, Kitai T, Triposkiadis F (2019) Heart failure and liver disease: cardiohepatic interactions. JACC Heart Fail 7(2):87–97. https://doi.org/10.1016/j.jchf.2018.10.007
Styczynski G, Milewska A, Marczewska M et al (2016) Echocardiographic correlates of abnormal liver tests in patients with exacerbation of chronic heart failure. J Am Soc Echocardiogr 29(2):132–139. https://doi.org/10.1016/j.echo.2015.09.012
Saito Y, Kato M, Nagashima K et al (2018) Prognostic relevance of liver stiffness assessed by transient elastography in patients with acute decompensated heart failure. Circ J 82(7):1822–1829. https://doi.org/10.1253/circj.CJ-17-1344
Taniguchi T, Sakata Y, Ohtani T et al (2014) Usefulness of transient elastography for noninvasive and reliable estimation of right-sided filling pressure in heart failure. Am J Cardiol 113(3):552–558. https://doi.org/10.1016/j.amjcard.2013.10.018
Tirado-Conte G, Rodes-Cabau J, Rodriguez-Olivares R et al (2018) Clinical outcomes and prognosis markers of patients with liver disease undergoing transcatheter aortic valve replacement: a propensity score-matched analysis. Circ Cardiovasc Interv 11(3):e005727. https://doi.org/10.1161/CIRCINTERVENTIONS.117.005727
Simonetto DA, Piccolo Serafim L, Gallo de Moraes A, Gajic O, Kamath PS (2019) Management of sepsis in patients with cirrhosis: current evidence and practical approach. Hepatology 70(1):418–428. https://doi.org/10.1002/hep.30412
Tandon P, Garcia-Tsao G (2008) Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis 28(1):26–42. https://doi.org/10.1055/s-2008-1040319
Stein JH, Neumann A, Preston LM et al (1997) Echocardiography for hemodynamic assessment of patients with advanced heart failure and potential heart transplant recipients. J Am Coll Cardiol 30(7):1765–1772. https://doi.org/10.1016/s0735-1097(97)00384-7
Acknowledgements
We thank Dr. Meghan Lucas for her critical reading of the manuscript.
Funding
Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Grant No. 397484323–TRR259.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Drs. Sinning, Grube, Tiyerili, Zimmer, Adam and Nickenig have received speaker honoraria and research grants from Abbott, Abiomed, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Veulemans has received speaker and/or study honoraria from Edwards Lifesciences and Medtronic. Dr. Kelm has received institutional grant support and/or personal fees from Philips, Abott, Medtronik, Boston Scientific, Mars, Boehringer Ingelheim, Daiichi-Sankyo GmbH, Amgen, Ancora Heart, and B. Braun. Dr. Grube is a proctor for Boston Scientific and Medtronic. Dr. Sudo has received manuscript fees from Boston Scientific Japan KK. The other authors report no conflicts of interest.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sudo, M., Shamekhi, J., Sedaghat, A. et al. Predictive value of the Fibrosis-4 index in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Clin Res Cardiol 111, 1367–1376 (2022). https://doi.org/10.1007/s00392-022-02055-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00392-022-02055-6