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Clinical and Echocardiographic Correlates of Elevated Troponin in Amyloid Light-Chain Cardiac Amyloidosis

      Increased troponin is associated with poor survival in patients with amyloid light-chain (AL) amyloidosis with cardiac involvement (CAL). The purpose of this investigation was to define the relation between increased troponin and clinical, morphologic, and functional features. The comparative utility of clinical, echocardiographic, and biochemical measurements in predicting survival in CAL was also investigated. One hundred seventeen patients with CAL were divided into 2 groups: normal troponin I (<0.06 ng/ml, n = 42) or increased troponin I (≥0.06 ng/ml, n = 75). Patients in the high troponin I group were older (63 vs 58 years, p = 0.04), with higher B-type natriuretic peptide levels (1,417 vs 936 pg/ml, p = 0.0004). The high troponin I group also had higher echocardiography-determined early/late mitral inflow velocity ratio (2.2 vs 1.4, p = 0.005) and myocardial performance index (0.59 vs 0.45, p = 0.04) and lower stroke index (28 vs 38 ml/beat/m2, p <0.0001) and left atrial systolic force (5.9 vs 8.4 k-dynes, p = 0.037) than the normal troponin group. Median survival was significantly shorter in the high troponin group (11 vs 45 months, p <0.001). At time of CAL diagnosis, univariate predictors of all-cause mortality included increased troponin, older age, male gender, New York Heart Association class III to IV, >2 organs involved, higher B-type natriuretic peptide, lower creatinine clearance, greater ventricular septal thickness, and higher myocardial performance index. However, by multivariate Cox survival analysis, only increased troponin was a significant predictor for all-cause mortality (hazard ratio 3.1, p = 0.002). In conclusion, increased troponin is associated with worse left ventricular and left atrial functions by echocardiography in patients with CAL. Among baseline variables, it is the strongest predictor of all-cause mortality in multivariate analysis. Troponin is a powerful tool in clinical and prognostic assessments of patients with CAL.
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      References

        • Roberts W.C.
        • Waller B.F.
        Cardiac amyloidosis causing cardiac dysfunction: analysis of 54 necropsy patients.
        Am J Cardiol. 1983; 52: 137-146
        • Bahlis N.J.
        • Lazarus H.M.
        Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted?.
        Bone Marrow Transplant. 2006; 38: 7-15
        • Kyle R.A.
        • Gertz M.A.
        Primary systemic amyloidosis: clinical and laboratory features in 474 cases.
        Semin Hematol. 1995; 32: 45-59
        • Kyle R.A.
        • Gertz M.A.
        • Greipp P.R.
        • Witzig T.E.
        • Lust J.A.
        • Lacy M.Q.
        • Therneau T.M.
        Long-term survival (10 years or more) in 30 patients with primary amyloidosis.
        Blood. 1999; 93: 1062-1066
        • Dispenzieri A.
        • Kyle R.A.
        • Gertz M.A.
        • Therneau T.M.
        • Miller W.L.
        • Chandrasekaran K.
        • McConnell J.P.
        • Burritt M.F.
        • Jaffe A.S.
        Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins.
        Lancet. 2003; 361: 1787-1789
        • Palladini G.
        • Campana C.
        • Klersy C.
        • Balduini A.
        • Vadacca G.
        • Perfetti V.
        • Perlini S.
        • Obici L.
        • Ascari E.
        • D'Eril G.M.
        • Moratti R.
        • Merlini G.
        Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis.
        Circulation. 2003; 107: 2440-2445
        • Selvanayagam J.B.
        • Hawkins P.N.
        • Paul B.
        • Myerson S.G.
        • Neubauer S.
        Evaluation and management of the cardiac amyloidosis.
        J Am Coll Cardiol. 2007; 50: 2101-2110
        • Comenzo R.L.
        How I treat amyloidosis.
        Blood. 2009; 114: 3147-3157
        • Lebovic D.
        • Hoffman J.
        • Levine B.M.
        • Hassoun H.
        • Landau H.
        • Goldsmith Y.
        • Maurer M.S.
        • Steingart R.M.
        • Cohen A.D.
        • Comenzo R.L.
        Predictors of survival in patients with systemic light-chain amyloidosis and cardiac involvement initially ineligible for stem cell transplantation and treated with oral melphalan and dexamethasone.
        Br J Haematol. 2008; 143: 369-373
        • Cueto-Garcia L.
        • Reeder G.S.
        • Kyle R.A.
        • Wood D.L.
        • Seward J.B.
        • Naessens J.
        • Offord K.P.
        • Greipp P.R.
        • Edwards W.D.
        • Tajik A.J.
        Echocardiographic findings in systemic amyloidosis: spectrum of cardiac involvement and relation to survival.
        J Am Coll Cardiol. 1985; 6: 737-743
        • Klein A.L.
        • Hatle L.K.
        • Taliercio C.P.
        • Oh J.K.
        • Kyle R.A.
        • Gertz M.A.
        • Bailey K.R.
        • Seward J.B.
        • Tajik A.J.
        Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis.
        Circulation. 1991; 83: 808-816
        • Kyle R.A.
        • Greipp P.R.
        • O'Fallon W.M.
        Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases.
        Blood. 1986; 68: 220-224
        • Tei C.
        • Dujardin K.S.
        • Hodge D.O.
        • Kyle R.A.
        • Tajik A.J.
        • Seward J.B.
        Doppler index combining systolic and diastolic myocardial performance: clinical value in cardiac amyloidosis.
        J Am Coll Cardiol. 1996; 28: 658-664
        • Gertz M.A.
        • Comenzo R.
        • Falk R.H.
        • Fermand J.P.
        • Hazenberg B.P.
        • Hawkins P.N.
        • Merlini G.
        • Moreau P.
        • Ronco P.
        • Sanchorawala V.
        • Sezer O.
        • Solomon A.
        • Grateau G.
        Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18–22 April 2004.
        Am J Hematol. 2005; 79: 319-328
        • Lang R.M.
        • Bierig M.
        • Devereux R.B.
        • Flachskampf F.A.
        • Foster E.
        • Pellikka P.A.
        • Picard M.H.
        • Roman M.J.
        • Seward J.
        • Shanewise J.S.
        • Solomon S.D.
        • Spencer K.T.
        • Sutton M.S.
        • Stewart W.J.
        • Chamber Quantification Writing Group, American Society of Echocardiography's Guidelines and Standards Committee, European Association of Echocardiography
        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. 2005; 18: 1440-1463
        • Manning W.J.
        • Silverman D.I.
        • Katz S.E.
        • Douglas P.S.
        Atrial ejection force: a noninvasive assessment of atrial systolic function.
        J Am Coll Cardiol. 1993; 22: 221-225
        • Cantwell R.V.
        • Aviles R.J.
        • Bjornsson J.
        • Wright R.S.
        • Freeman W.K.
        • Oh J.K.
        • Hoyer J.D.
        • Markovic S.
        • Jaffe A.S.
        Cardiac amyloidosis presenting with elevations of cardiac troponin I and angina pectoris.
        Clin Cardiol. 2002; 25: 33-37
        • Miller W.L.
        • Wright R.S.
        • McGregor C.G.
        • Dispenzieri A.
        • McConnell J.P.
        • Burritt M.F.
        • Jaffe A.S.
        Troponin levels in patients with amyloid cardiomyopathy undergoing cardiac transplantation.
        Am J Cardiol. 2001; 88: 813-815
        • Syed I.S.
        • Glockner J.F.
        • Feng D.
        • Araoz P.A.
        • Martinez M.W.
        • Edwards W.D.
        • Gertz M.A.
        • Dispenzieri A.
        • Oh J.K.
        • Bellavia D.
        • Tajik A.J.
        • Grogan M.
        Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis.
        JACC Cardiovasc Imaging. 2010; 3: 155-164
        • Capone R.
        • Amsterdam E.A.
        • Mason D.T.
        • Zelis R.
        Systemic amyloidosis, functional coronary insufficiency, and autonomic impairment.
        Ann Intern Med. 1972; 76: 599-603
        • Kinnunen P.
        • Vuolteenaho O.
        • Ruskoaho H.
        Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching.
        Endocrinology. 1993; 132: 1961-1970
        • Takemura G.
        • Takatsu Y.
        • Doyama K.
        • Itoh H.
        • Saito Y.
        • Koshiji M.
        • Ando F.
        • Fujiwara T.
        • Nakao K.
        • Fujiwara H.
        Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis.
        J Am Coll Cardiol. 1998; 31: 745-765
        • Nordlinger M.
        • Magnani B.
        • Skinner M.
        • Falk R.H.
        Is elevated plasma B-natriuretic peptide in amyloidosis simply a function of the presence of heart failure?.
        Am J Cardiol. 2005; 96: 982-984
        • Dispenzieri A.
        • Gertz M.A.
        • Kyle R.A.
        • Lacy M.Q.
        • Burritt M.F.
        • Therneau T.M.
        • Greipp P.R.
        • Witzig T.E.
        • Lust J.A.
        • Rajkumar S.V.
        • Fonseca R.
        • Zeldenrust S.R.
        • McGregor C.G.
        • Jaffe A.S.
        Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: A staging system for primary systemic amyloidosis.
        J Clin Oncol. 2004; 22: 3751-3757
        • Kristen A.V.
        • Perz J.B.
        • Schonland S.O.
        • Hegenbart U.
        • Schnabel P.A.
        • Kristen J.H.
        • Goldschmidt H.
        • Katus H.A.
        • Dengler T.J.
        Non-invasive predictors of survival in cardiac amyloidosis.
        Eur J Heart Fail. 2007; 9: 617-624
        • Bellavia D.
        • Pellikka P.A.
        • Al-Zahrani G.B.
        • Abraham T.P.
        • Dispenzieri A.
        • Miyazaki C.
        • Lacy M.
        • Scott C.G.
        • Oh J.K.
        • Miller F.A.
        Independent predictors of survival in primary systemic (Al) amyloidosis, including cardiac biomarkers and left ventricular strain imaging: an observational cohort study.
        J Am Soc Echocardiogr. 2010; 23: 643-652