Prognostic Utility of Troponin I and N Terminal-ProBNP among Patients with Heart Failure due to Non-Ischemic Cardiomyopathy and Important Correlations

Author(s): Tuoyo O. Mene-Afejuku*, Carissa Dumancas, Adedoyin Akinlonu, Olatunde Ola, Eder H. Cativo, Shushan Veranyan, Persio D. Lopez, Kwon S. Kim, Gerald Pekler, Savi Mushiyev, Ferdinand Visco

Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents

Volume 17 , Issue 2 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Heart Failure (HF) is accompanied by a high cost of care and gloomy prognosis despite recent advances in its management. Therefore, efforts to minimize HF rehospitalizations is a major focus of several studies.

Methods: We conducted a retrospective cohort study of 140 patients 18 years and above who had baseline clinical parameters, echocardiography, NT-ProBNP, troponin I and other laboratory parameters following a 3-year electronic medical record review. Patients with coronary artery disease, preserved ejection fraction, pulmonary embolism, cancer, and end-stage renal disease were excluded.

Results: Of the 140 patients admitted with HF with reduced Ejection Fraction (HFrEF) secondary to non-ischemic cardiomyopathy, 15 were re-hospitalized within 30 days of discharge while 42 were rehospitalized within 6 months after discharge for decompensated HF. Receiver operating characteristic (ROC) cutoff points were obtained for NT-ProBNP at 5178 pg/ml and serum troponin I at 0.045 ng/ml. After Cox regression analysis, patients with HFrEF who had higher hemoglobin levels had reduced odds of re-hospitalization (p = 0.007) within 30 days after discharge. NT-ProBNP and troponin I were independent predictors of re-hospitalization at 6 months after discharge (p = 0.047 and p = 0.02), respectively, after Cox regression analysis.

Conclusion: Troponin I and NT-ProBNP at admission are the best predictors of re-hospitalization 6 months after discharge among patients with HFrEF. Hemoglobin is the only predictor of 30 -day rehospitalization among HFrEF patients in this study. High-risk patients may require aggressive therapy to improve outcomes.

Keywords: Heart failure, re-hospitalization, troponin, cardiomyopathy, reduced ejection fraction, hemoglobin.

Gheorghiade, M.; Vaduganathan, M.; Fonarow, G.C.; Bonow, R.O. Rehospitalization for heart failure: Problems and perspectives. J. Am. Coll. Cardiol., 2013, 61(4), 391-403.
[] [PMID: 23219302]
Omar, H.R.; Guglin, M. Characteristics and outcomes of patients with acute systolic heart failure discharged within 48 hours: A qualification for “observation status” hospital admission. Int. J. Cardiol., 2016, 223, 129-132.
[] [PMID: 27537738]
Yancy, C.W.; Jessup, M.; Bozkurt, B. 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol., 2013, 62(16), 1495-1539.
[] [PMID: 23747642]
Go, A.S.; Mozaffarian, D.; Roger, V.L.; Benjamin, E.J.; Berry, J.D.; Borden, W.B.; Bravata, D.M.; Dai, S.; Ford, E.S.; Fox, C.S.; Franco, S.; Fullerton, H.J.; Gillespie, C.; Hailpern, S.M.; Heit, J.A.; Howard, V.J.; Huffman, M.D.; Kissela, B.M.; Kittner, S.J.; Lackland, D.T.; Lichtman, J.H.; Lisabeth, L.D.; Magid, D.; Marcus, G.M.; Marelli, A.; Matchar, D.B.; McGuire, D.K.; Mohler, E.R.; Moy, C.S.; Mussolino, M.E.; Nichol, G.; Paynter, N.P.; Schreiner, P.J.; Sorlie, P.D.; Stein, J.; Turan, T.N.; Virani, S.S.; Wong, N.D.; Woo, D.; Turner, M.B. Heart disease and stroke statistics-2013 update: A report from the American Heart Association. Circulation, 2013, 127(1), e6-e245.
[] [PMID: 23239837]
Dunlay, S.M.; Shah, N.D.; Shi, Q.; Morlan, B.; Van Houten, H.; Long, K.H.; Roger, V.L. Lifetime costs of medical care after heart failure diagnosis. Circ. Cardiovasc. Qual. Outcomes, 2011, 4(1), 68-75.
[] [PMID: 21139091]
Pitt, B.; Segal, R.; Martinez, F.A.; Meurers, G.; Cowley, A.J.; Thomas, I.; Deedwania, P.C.; Ney, D.E.; Snavely, D.B.; Chang, P.I. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet, 1997, 349(9054), 747-752.
[] [PMID: 9074572]
Follath, F. Nonischemic heart failure: Epidemiology, pathophysiology, and progression of disease. J. Cardiovasc. Pharmacol., 1999, 33(Suppl. 3), S31-S35.
[PMID: 10442682]
McMurray, J.J.; Adamopoulos, S.; Anker, S.D.; Auricchio, A.; Böhm, M.; Dickstein, K.; Falk, V.; Filippatos, G.; Fonseca, C.; Gomez-Sanchez, M.A.; Jaarsma, T.; Køber, L.; Lip, G.Y.; Maggioni, A.P.; Parkhomenko, A.; Pieske, B.M.; Popescu, B.A.; Rønnevik, P.K.; Rutten, F.H.; Schwitter, J.; Seferovic, P.; Stepinska, J.; Trindade, P.T.; Voors, A.A.; Zannad, F.; Zeiher, A. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur. Heart J., 2012, 33(14), 1787-1847.
[] [PMID: 22611136]
McKie, P.M.; Burnett, J.C. NT-proBNP: The gold standard biomarker in heart failure. J. Am. Coll. Cardiol., 2016, 68(22), 2437-2439.
[] [PMID: 27908348]
Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Simoons, M.L.; Chaitman, B.R.; White, H.D.; Thygesen, K.; Alpert, J.S.; White, H.D.; Jaffe, A.S.; Katus, H.A.; Apple, F.S.; Lindahl, B.; Morrow, D.A.; Chaitman, B.R.; Clemmensen, P.M.; Johanson, P.; Hod, H.; Underwood, R.; Bax, J.J.; Bonow, J.J.; Pinto, F.; Gibbons, R.J.; Fox, K.A.; Atar, D.; Newby, L.K.; Galvani, M.; Hamm, C.W.; Uretsky, B.F.; Steg, P.G.; Wijns, W.; Bassand, J.P.; Menasche, P.; Ravkilde, J.; Ohman, E.M.; Antman, E.M.; Wallentin, L.C.; Armstrong, P.W.; Simoons, M.L.; Januzzi, J.L.; Nieminen, M.S.; Gheorghiade, M.; Filippatos, G.; Luepker, R.V.; Fortmann, S.P.; Rosamond, W.D.; Levy, D.; Wood, D.; Smith, S.C.; Hu, D.; Lopez-Sendon, J.L.; Robertson, R.M.; Weaver, D.; Tendera, M.; Bove, A.A.; Parkhomenko, A.N.; Vasilieva, E.J.; Mendis, S.; Bax, J.J.; Baumgartner, H.; Ceconi, C.; Dean, V.; Deaton, C.; Fagard, R.; Funck-Brentano, C.; Hasdai, D.; Hoes, A.; Kirchhof, P.; Knuuti, J.; Kolh, P.; McDonagh, T.; Moulin, C.; Popescu, B.A.; Reiner, Z.; Sechtem, U.; Sirnes, P.A.; Tendera, M.; Torbicki, A.; Vahanian, A.; Windecker, S.; Morais, J.; Aguiar, C.; Almahmeed, W.; Arnar, D.O.; Barili, F.; Bloch, K.D.; Bolger, A.F.; Botker, H.E.; Bozkurt, B.; Bugiardini, R.; Cannon, C.; de Lemos, J.; Eberli, F.R.; Escobar, E.; Hlatky, M.; James, S.; Kern, K.B.; Moliterno, D.J.; Mueller, C.; Neskovic, A.N.; Pieske, B.M.; Schulman, S.P.; Storey, R.F.; Taubert, K.A.; Vranckx, P.; Wagner, D.R. Third universal definition of myocardial infarction. J. Am. Coll. Cardiol., 2012, 60(16), 1581-1598.
[] [PMID: 22958960]
Almeida, A.G. NT-proBNP and myocardial fibrosis: The invisible link between health and disease. J. Am. Coll. Cardiol., 2017, 70(25), 3110-3112.
[] [PMID: 29268925]
Richards, A.M. N-terminal B-type natriuretic peptide in heart failure. Heart Fail. Clin., 2018, 14(1), 27-39.
[] [PMID: 29153198]
Davarzani, N.; Sanders-van Wijk, S.; Karel, J.; Maeder, M.T.; Leibundgut, G.; Gutmann, M.; Pfisterer, M.E.; Rickenbacher, P.; Peeters, R.; Brunner-la Rocca, H.P. N-terminal Pro-B-type natriuretic peptide-guided therapy in chronic heart failure reduces repeated hospitalizations-results from TIME-CHF. J. Card. Fail., 2017, 23(5), 382-389.
[] [PMID: 28232046]
Januzzi, J.L.; Van Kimmenade, R.; Lainchbury, J.; Bayes-Genis, A.; Ordonez-Llanos, J.; Santalo-Bel, M.; Pinto, Y.M.; Richards, M. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: An international pooled analysis of 1256 patients: The international collaborative of NT-proBNP study. Eur. Heart J., 2006, 27(3), 330-337.
[] [PMID: 16293638]
Golcuk, Y.; Golcuk, B.; Velibey, Y.; Oray, D.; Atilla, O.D.; Colak, A.; Kurtulmus, Y.; Yildirim, A.; Eren, M. Predictive cutoff point of admission N-terminal pro-B-type natriuretic peptide testing in the ED for prognosis of patients with acute heart failure. Am. J. Emerg. Med., 2013, 31(8), 1191-1195.
[] [PMID: 23759684]
Potter, J.M.; Simpson, A.J.; Kerrigan, J.; Southcott, E.; Salib, M.M.; Koerbin, G.; Hickman, P.E. The relationship of plasma creatinine (as eGFR) and high-sensitivity cardiac troponin and NT-proBNP concentrations in a hospital and community outpatient population. Clin. Biochem., 2017, 50(15), 813-815.
[] [PMID: 28392226]
Menzorov, M.V.; Shutov, A.M.; Midlenko, V.I.; Larionova, N.V.; Morozova, I.V.; Akulova, O.V. Value of N-terminal pro brain natriuretic peptide in predicting acute kidney injury in patients with acute decompensated chronic heart failure Ter. Arkh., 2017, 89(3), 78-84.
[] [PMID: 28378735]
Ibrahim, N.E.; Gaggin, H.K.; Rabideau, D.J.; Gandhi, P.U.; Mallick, A.; Januzzi, J.L. Worsening renal function during management for chronic heart failure with reduced ejection fraction: Results from the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study. J. Card. Fail., 2017, 23(2), 121-130.
[] [PMID: 27469482]
Nagarajan, V.; Kohan, L.; Holland, E.; Keeley, E.C.; Mazimba, S. Obesity paradox in heart failure: A heavy matter. ESC Heart Fail., 2016, 3(4), 227-234.
[] [PMID: 27867523]
Van Kimmenade, R.; Van Dielen, F.; Bakker, J.; Nijhuis, J.; Crijns, H.; Buurman, W.; Van Dieijen-Visser, M.; Greve, J.W.; Pinto, Y. Is brain natriuretic peptide production decreased in obese subjects? J. Am. Coll. Cardiol., 2006, 47(4), 886-887.
[] [PMID: 16487862]
Lavie, C.J.; Alpert, M.A.; Arena, R.; Mehra, M.R.; Milani, R.V.; Ventura, H.O. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail., 2013, 1(2), 93-102.
[] [PMID: 24621833]
Horwich, T.B.; Hamilton, M.A.; Fonarow, G.C. B-type natriuretic peptide levels in obese patients with advanced heart failure. J. Am. Coll. Cardiol., 2006, 47(1), 85-90.
[] [PMID: 16386669]
Gaggin, H.K.; Belcher, A.M.; Gandhi, P.U.; Ibrahim, N.E.; Januzzi, J.L. Serial echocardiographic characteristics, novel biomarkers and cachexia development in patients with stable chronic heart failure. J. Cardiovasc. Transl. Res., 2016, 9(5-6), 429-431.
[] [PMID: 27631883]
Wettersten, N.; Maisel, A. Role of cardiac troponin levels in acute heart failure. Card. Fail. Rev., 2015, 1(2), 102-106.
[] [PMID: 28785441]
Kociol, R.D.; Pang, P.S.; Gheorghiade, M.; Fonarow, G.C.; O’Connor, C.M.; Felker, G.M. Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J. Am. Coll. Cardiol., 2010, 56(14), 1071-1078.
[] [PMID: 20863950]
Januzzi, J.L.; Filippatos, G.; Nieminen, M.; Gheorghiade, M. Troponin elevation in patients with heart failure: On behalf of the third Universal definition of myocardial infarction global task force: Heart failure section. Eur. Heart J., 2012, 33(18), 2265-2271.
[] [PMID: 22745356]
Hessel, M.H.; Atsma, D.E.; Van Der Valk, E.J.; Bax, W.H.; Schalij, M.J.; Van Der Laarse, A. Release of cardiac troponin I from viable cardiomyocytes is mediated by integrin stimulation. Pflugers Arch., 2008, 455(6), 979-986.
[] [PMID: 17909848]
Sato, Y.; Kita, T.; Takatsu, Y.; Kimura, T. Biochemical markers of myocyte injury in heart failure. Heart, 2004, 90(10), 1110-1113.
[] [PMID: 15367501]
Peacock, W.F.; De Marco, T.; Fonarow, G.C.; Diercks, D.; Wynne, J.; Apple, F.S.; Wu, A.H. Cardiac troponin and outcome in acute heart failure. N. Engl. J. Med., 2008, 358(20), 2117-2126.
[] [PMID: 18480204]
You, J.J.; Austin, P.C.; Alter, D.A.; Ko, D.T.; Tu, J.V. Relation between cardiac troponin I and mortality in acute decompensated heart failure. Am. Heart J., 2007, 153(4), 462-470.
[] [PMID: 17383280]
Perna, E.R.; Macín, S.M.; Parras, J.I.; Pantich, R.; Farías, E.F.; Badaracco, J.R.; Jantus, E.; Medina, F.; Brizuela, M. Cardiac troponin T levels are associated with poor short- and long-term prognosis in patients with acute cardiogenic pulmonary edema. Am. Heart J., 2002, 143(5), 814-820.
[] [PMID: 12040342]
Chan, W.W.; Waltman Johnson, K; Friedman, H.S. Association between cardiac, renal, and hepatic biomarkers and outcomes in patients with acute heart failure. Hosp. Pract. (1995)., 2016, 44(3), 138-145.
Wallenborn, J.; Marx, A.; Störk, S.; Güder, G.; Brenner, S.; Ertl, G.; Angermann, C.E. Prognostic significance of serial high-sensitivity troponin I measurements following acute cardiac decompensation-correlation with longer-term clinical outcomes and reverse remodelling. Int. J. Cardiol., 2017, 232, 199-207.
[] [PMID: 28094131]
Perna, E.R.; Aspromonte, N.; Cimbaro Canella, J.P.; Di Tano, G.; Macin, S.M.; Feola, M.; Coronel, M.L.; Milani, L.; Parras, J.I.; Milli, M.; García, E.H.; Valle, R. Minor myocardial damage is a prevalent condition in patients with acute heart failure syndromes and preserved systolic function with long-term prognostic implications: A report from the CIAST-HF (Collaborative Italo-Argentinean Study on cardiac Troponin T in Heart Failure) study. J. Card. Fail., 2012, 18(11), 822-830.
[] [PMID: 23141854]
Demissei, B.G.; Postmus, D.; Cleland, J.G.; O’Connor, C.M.; Metra, M.; Ponikowski, P.; Teerlink, J.R.; Cotter, G.; Davison, B.A.; Givertz, M.M.; Bloomfield, D.M.; Van Veldhuisen, D.J.; Dittrich, H.C.; Hillege, H.L.; Voors, A.A. Plasma biomarkers to predict or rule out early post-discharge events after hospitalization for acute heart failure. Eur. J. Heart Fail., 2017, 19(6), 728-738.
[] [PMID: 28251755]
Cheng, H.; Fan, W.Z.; Wang, S.C.; Geng, J.; Zang, H.L.; Shen, X.H.; Liu, Z.H.; Wang, L.Z. Prognostic utility of combination of NT-proBNP with high sensitive cTn I in patients with heart failure: Results from retrospective study in an emergency department. Scand. J. Clin. Lab. Invest., 2016, 76(5), 361-367.
[] [PMID: 27228479]
Busse, J.C.; Cohn, T.M.; Butao, R.; Lamoureux, J. Association between Severity of Anemia and 30-Day Readmission Rate: Archival Data of 847 Patients with Acute Decompensated Heart Failure., 2014.
Silverberg, D.S.; Wexler, D.; Iaina, A.; Schwartz, D. The role of correction of anaemia in patients with congestive heart failure: A short review. Eur. J. Heart Fail., 2008, 10(9), 819-823.
[] [PMID: 18703380]
Caramelo, C.; Justo, S.; Gil, P. Anemia in heart failure: Pathophysiology, pathogenesis, treatment, and incognitae. Rev. Esp. Cardiol., 2007, 60(8), 848-860.
[] [PMID: 17688854]
Zaya, M.; Phan, A.; Schwarz, E.R. Predictors of re-hospitalization in patients with chronic heart failure. World J. Cardiol., 2012, 4(2), 23-30.
[] [PMID: 22379534]
Felker, G.M.; Gattis, W.A.; Leimberger, J.D.; Adams, K.F.; Cuffe, M.S.; Gheorghiade, M.; O’Connor, C.M. Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am. J. Cardiol., 2003, 92(5), 625-628.
[] [PMID: 12943893]
Felker, G.M.; Adams, K.F.; Gattis, W.A.; O’Connor, C.M. Anemia as a risk factor and therapeutic target in heart failure. J. Am. Coll. Cardiol., 2004, 44(5), 959-966.
[] [PMID: 15337204]
Lelli, D.; Antonelli Incalzi, R.; Pedone, C. Hemoglobin concentration influences N-terminal pro B-type natriuretic peptide levels in hospitalized older adults with and without heart failure. J. Am. Geriatr. Soc., 2017, 65(11), 2369-2373.
[] [PMID: 28556898]
Stojcevski, B.; Celic, V.; Navarin, S.; Pencic, B.; Majstorovic, A.; Sljivic, A.; Magrini, L.; Cristofano, F.; Cavalieri, L.; Di Somma, S. The use of discharge haemoglobin and NT-proBNP to improve short and long-term outcome prediction in patients with acute heart failure. Eur. Heart J. Acute Cardiovasc. Care, 2017, 6(8), 676-684.
[] [PMID: 25943556]
Kansagara, D.; Dyer, E.; Englander, H.; Fu, R.; Freeman, M.; Kagen, D. Treatment of anemia in patients with heart disease: A systematic review. Ann. Intern. Med., 2013, 159(11), 746-757.
[] [PMID: 24297191]
Qaseem, A.; Humphrey, L.L.; Fitterman, N.; Starkey, M.; Shekelle, P. Treatment of anemia in patients with heart disease: A clinical practice guideline from the American College of Physicians. Ann. Intern. Med., 2013, 159(11), 770-779.
[] [PMID: 24297193]
Swedberg, K.; Young, J.B.; Anand, I.S.; Cheng, S.; Desai, A.S.; Diaz, R.; Maggioni, A.P.; McMurray, J.J.; O’Connor, C.; Pfeffer, M.A.; Solomon, S.D.; Sun, Y.; Tendera, M.; Van Veldhuisen, D.J. Treatment of anemia with darbepoetin alfa in systolic heart failure. N. Engl. J. Med., 2013, 368(13), 1210-1219.
[] [PMID: 23473338]

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [94 - 103]
Pages: 10
DOI: 10.2174/1871525717666190717160615

Article Metrics

PDF: 36