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Liver dysfunction as predictor of prognosis in patients with amyloidosis: utility of the Model for End-stage Liver disease (MELD) scoring system

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Abstract

Amyloidosis prognosis is often related to the onset of heart failure and a worsening that is concomitant with kidney–liver dysfunction; thus the Model for End-stage Liver disease (MELD) may be an ideal instrument to summarize renal–liver function. Our aim has been to test the MELD score as a prognostic tool in amyloidosis. We evaluated 128 patients, 46 with TTR-related amyloidosis and 82 with AL amyloidosis. All patients had a complete clinical and echocardiography evaluation; overall biohumoral assessment included troponin I, NT-proBNP, creatinine, total bilirubin and INR ratio. The study population was dichotomized at the 12 cut-off level of MELD scores; those with MELD score >12 had a lower survival compared to controls in the study cohort (40.7 vs 66.3 %; p = 0.006). Either as a continuous and dichotomized variable, MELD shows its independent prognostic value at multivariable analysis (HR = 1.199, 95 % CI 1.082–1.329; HR = 2.707, 95 % CI 1.075–6.817, respectively). MELD shows a lower prognostic sensitivity/specificity ratio than troponin I and NT-proBNP in the whole study population and AL subgroup, while in TTR patients MELD has a higher sensitivity/specificity ratio compared to troponin and NT-proBNP (ROC analysis-AUC: 0.853 vs 0.726 vs 0.659). MELD is able to predict prognosis in amyloidosis. A MELD score >12 selects a subgroup of patients with a higher risk of death. The predictive accuracy seems to be more evident in TTR patients in whom currently no effective scoring systems have been validated.

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References

  1. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, Laumann K, Zeldenrust SR, Leung N, Dingli D, Greipp PR, Lust JA, Russell SJ, Kyle RA, Rajkumar SV, Gertz MA (2012) Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 30:989–995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, Greipp PR, Witzig TE, Lust JA, Rajkumar SV, Fonseca R, Zeldenrust SR, McGregor CG, Jaffe AS (2004) Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol 22:3751–3757

    Article  CAS  PubMed  Google Scholar 

  3. Kumar SK, Gertz MA, Lacy MQ, Dingli D, Hayman SR, Buadi FK, Short-Detweiler K, Zeldenrust SR, Leung N, Greipp PR, Lust JA, Russell SJ, Kyle RA, Rajkumar SV, Dispenzieri A (2011) Recent improvements in survival in primary systemic amyloidosis and the importance of an early mortality risk score. Mayo Clin Proc 86:12–18

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kristen AV, Scherer K, Buss S, Aus dem Siepen F, Haufe S, Bauer R, Hinderhofer K, Giannitsis E, Hardt S, Haberkorn U, Katus HA, Steen H (2014) Noninvasive risk stratification of patients with transthyretin amyloidosis. JACC Cardiovasc Imaging 7:502–510

    Article  PubMed  Google Scholar 

  5. Palladini G, Lavatelli F, Russo P, Russo P, Perlini S, Perfetti V, Bosoni T, Obici L, Bradwell AR, D’Eril GM, Fogari R, Moratti R, Merlini G (2006) Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 107:3854–3858

    Article  CAS  PubMed  Google Scholar 

  6. Palladini G, Barassi A, Klersy C, Pacciolla R, Milani P, Sarais G, Perlini S, Albertini R, Russo P, Foli A, Bragotti LZ, Obici L, Moratti R (2010) Melzi d’Eril GV, Merlini G. The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood 116:3426–3430

    Article  CAS  PubMed  Google Scholar 

  7. Dispenzieri A, Gertz MA, Kumar SK, Lacy MQ, Kyle RA, Saenger AK, Grogan M, Zeldenrust SR, Hayman SR, Buadi F, Greipp PR, Leung N, Russell SR, Dingli D, Lust JA, Rajkumar SV, Jaffe AS (2014) High sensitivity cardiac troponin T in patients with immunoglobulin light chain amyloidosis. Heart 100:383–388

    Article  CAS  PubMed  Google Scholar 

  8. Buss SJ, Emami M, Mereles D, Korosoglou G, Kristen AV, Voss A, Schellberg D, Zugck C, Galuschky C, Giannitsis E, Hegenbart U, Ho AD, Katus HA, Schonland SO, Hardt SE (2012) Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers. J Am Coll Cardiol 60:1067–1076

    Article  PubMed  Google Scholar 

  9. Bellavia D, Pellikka PA, Dispenzieri A, Scott CG, Al-Zahrani GB, Grogan M, Pitrolo F, Oh JK, Miller FA Jr (2012) Comparison of right ventricular longitudinal strain imaging, tricuspid annular plane systolic excursion, and cardiac biomarkers for early diagnosis of cardiac involvement and risk stratification in primary systematic (AL) amyloidosis: a 5-year cohort study. Eur Heart J Cardiovasc Imaging 13:680–689

    Article  PubMed  Google Scholar 

  10. Bellavia D, Abraham RS, Pellikka PA, Dispenzieri A, Burnett JC Jr, Al-Zahrani GB, Green TD, Manske MK, Gertz MA, Miller FA Jr, Abraham TP (2011) Utility of Doppler myocardial imaging, cardiac biomarkers, and clonal immunoglobulin genes to assess left ventricular performance and stratify risk following peripheral blood stem cell transplantation in patients with systemic light chain amyloidosis (Al). J Am Soc Echocardiogr 24:444–454

    Article  PubMed  PubMed Central  Google Scholar 

  11. Perlini S, Salinaro F, Musca F, Mussinelli R, Boldrini M, Raimondi A, Milani P, Foli A, Cappelli F, Perfetto F, Palladini G, Rapezzi C, Merlini G (2014) Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis. J Hypertens 32:1121–1131

    Article  CAS  PubMed  Google Scholar 

  12. Cappelli F, Porciani MC, Bergesio F, Perlini S, Attanà P, Moggi Pignone A, Salinaro F, Musca F, Padeletti L, Perfetto F (2012) Right ventricular function in AL amyloidosis: characteristics and prognostic implication. Eur Heart J Cardiovasc Imaging 13:416–422

    Article  PubMed  Google Scholar 

  13. Perfetto F, Cappelli F, Bergesio F, Ciuti G, Porciani MC, Padeletti L, Moggi Pignone A (2013) Cardiac amyloidosis: the heart of the matter. Intern Emerg Med 8:191–203

    Article  PubMed  Google Scholar 

  14. Kamath PS, Wiesner RH, Malinhoc M, Kremers W, Therneau TM, Kosberg CL, D’Amico G, Dickson ER, Kim WR (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470

    Article  CAS  PubMed  Google Scholar 

  15. Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P, Kremers W, Lake J, Howard T, Merion RM, Wolfe RA, Krom R, United Network for Organ Sharing Liver Disease Severity Score Committee (2003) Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124:91–96

    Article  PubMed  Google Scholar 

  16. Kim MS, Kato TS, Farr M, Wu C, Givens RC, Collado E, Mancini DM, Schulze PC (2013) Hepatic dysfunction in ambulatory patients with heart failure: application of the MELD scoring system for outcome prediction. J Am Coll Cardiol 61:2253–2261

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bonde P, Ku NC, Genovese EA, Bermudez CA, Bhama JK, Ciarleglio MM, Cong X, Teuteberg JJ, Kormos RL (2012) Model for end-stage liver disease score predicts adverse events related to ventricular assist device therapy. Ann Thorac Surg 93:1541–1547

    Article  PubMed  Google Scholar 

  18. Yang JA, Kato TS, Shulman BP, Takayama H, Farr M, Jorde UP, Mancini DM, Naka Y, Schulze PC (2012) Liver dysfunction as a predictor of outcomes in patients with advanced heart failure requiring ventricular assist device support: use of the Model of End-stage Liver Disease (MELD) and MELD eXcluding INR (MELD-XI) scoring system. J Heart Lung Transplant 31:601–610

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tsuda K, Koide M, Kunii Y, Watanabe K, Miyairi S, Ohashi Y, Harada T (2013) Simplified model for end-stage liver disease score predicts mortality for tricuspid valve surgery. Interact CardioVasc Thorac Surg 16:630–635

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kato TS, Stevens GR, Jiang J, Schulze PC, Gukasyan N, Lippel M, Levin A, Homma S, Mancini D, Farr M (2013) Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation. J Heart Lung Transplant 32:333–340

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chokshi A, Cheema FH, Schaefle KJ, Jiang J, Collado E, Shahzad K, Khawaja T, Farr M, Takayama H, Naka Y, Mancini DM, Schulze PC (2012) Hepatic dysfunction and survival after orthotopic heart transplantation: application of the MELD scoring system for outcome prediction. J Heart Lung Transplant 31:591–600

    Article  PubMed  PubMed Central  Google Scholar 

  22. Van Deursen VM, Damman K, Hillege HL, van Beek AP, van Veldhuisen DJ, Voors AA (2010) Abnormal liver function in relation to hemodynamic profile in heart failure patients. J Card Fail 16:84–90

    Article  PubMed  Google Scholar 

  23. Ronco C, Cicoira M, McCullough PA (2012) Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol 60:1031–1042

    Article  PubMed  Google Scholar 

  24. Cappelli F, Baldasseroni S, Bergesio F, Padeletti L, Attanà P, Pignone AM, Grifoni E, Ciuti G, Fabbri A, Tarantini F, Marchionni N, Gensini GF, Perfetto F (2014) Biohumoral markers as predictor of right ventricular dysfunction in AL Amyloidosis. Amyloid 21:97–102

    Article  CAS  PubMed  Google Scholar 

  25. Falk RH (2005) Diagnosis and management of the cardiac amyloidoses. Circulation 112:2047–2060

    Article  PubMed  Google Scholar 

  26. Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L, Leone O, Farsad M, Ciliberti P, Bacchi-Reggiani L, Fallani F, Branzi A, Rapezzi C (2005) Non invasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol 46:1076–1084

    Article  PubMed  Google Scholar 

  27. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ, Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18:1440–1463

    Article  PubMed  Google Scholar 

  28. Braunwald E (2013) Heart Failure. JACC Heart Fail 1:1–20

    Article  PubMed  Google Scholar 

  29. Cappelli F, Baldasseroni S, Bergesio F, Perlini S, Salinaro F, Padeletti L, Attanà P, Paoletti Perini A, Moggi Pignone A, Grifoni E, Fabbri A, Marchionni N, Gensini GF, Perfetto F (2015) Echocardiographic and biohumoral characteristics in patients with AL and TTR amyloidosis at diagnosis. Clin Cardiol. 38(2):69–75

    Article  PubMed  Google Scholar 

  30. Cappelli F, Frusconi S, Bergesio F, Grifoni E, Fabbri A, Giuliani C, Falconi S, Bonifacio S, Perfetto F (2016) The Val142Ile transthyretin cardiac amyloidosis: not only an Afro-American pathogenic variant? A single-centre Italian experience. J Cardiovasc Med (Hagerstown). 17(2):122–125

    Article  CAS  Google Scholar 

  31. Perfetto F, Cappelli F, Bergesio F (2011) Asymptomatic homozygous gene carrier in a family with Ile68Leu ATTR amyloidosis: a new endemic region in northern Tuscany? J Cardiovasc Med (Hagerstown) 12(6):450–451

    Article  Google Scholar 

  32. Fontana M, Banypersad SM, Treibel TA, Maestrini V, Sado DM, White SK, Pica S et al (2014) Native T1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging 7:157–165

    Article  PubMed  Google Scholar 

  33. Hutt DF, Quigley AM, Page J, Hall ML, Burniston M, Gopaul D, Lane T et al (2014) Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging 15:1289–1298

    Article  PubMed  Google Scholar 

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Correspondence to Francesco Cappelli.

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All patients gave written informed consent for their clinical records to be used for research purposes, in accordance with Institutional Review Board guidelines.

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F. Cappelli and S. Baldasseroni equally contributed to the present manuscript.

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Supplementary material 1 Figure 1: Survival curves (KM) according to MELD score cut-off. (JPEG 25 kb)

11739_2016_1500_MOESM2_ESM.jpg

Supplementary material 2 Figure  2: Survival curves (KM) according to MELD score cut-off in the two amyloidosis etiologies. (JPEG 29 kb)

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Cappelli, F., Baldasseroni, S., Bergesio, F. et al. Liver dysfunction as predictor of prognosis in patients with amyloidosis: utility of the Model for End-stage Liver disease (MELD) scoring system. Intern Emerg Med 12, 23–30 (2017). https://doi.org/10.1007/s11739-016-1500-0

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  • DOI: https://doi.org/10.1007/s11739-016-1500-0

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