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Functional Cardiac Recovery and Hematologic Response to Chemotherapy in Patients With Light-Chain Amyloidosis (from the Stanford University Amyloidosis Registry)

      Cardiac involvement is common in patients with light-chain (AL) amyloidosis and portends a poor prognosis, although little is known about the changes in cardiac mechanics after chemotherapy. We sought to explore the relation between amyloidosis staging and baseline cardiac mechanics and to investigate short-term changes in cardiac mechanics after chemotherapy. We identified 41 consecutive patients from the Stanford Amyloid Center who had echocardiograms and free light-chain values before and after chemotherapy, along with 40 age- and gender-matched controls. Echocardiographic assessment included left ventricular global longitudinal strain, E/e' ratio, and left atrial (LA) stiffness. Hematologic response to chemotherapy was defined as ≥50% reduction in the difference between the involved and the uninvolved free light chain (dFLC). The mean age was 66.9 ± 8.4 years and 66% were men. Before chemotherapy, global longitudinal strain, E/e' ratio, and LA stiffness were impaired in patients with amyloidosis compared with controls, and the severity of impairment worsened with advanced staging. After chemotherapy, hematologic response was observed in 30 (73%) patients. There was a significant association between the change in dFLC and cardiac function (E/e' ratio: r = −0.43, p = 0.01; LA stiffness: r = −0.35, p = 0.05). There was no significant improvement in cardiac mechanics in patients without a hematologic response to chemotherapy. In conclusion, amyloidosis stage correlated with noninvasive measurements of cardiac mechanics, and improvement in dFLC correlated with cardiac improvement on short-term follow-up echocardiography.
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      References

        • Shah K.B.
        • Inoue Y.
        • Mehra M.R.
        Amyloidosis and the heart: a comprehensive review.
        Arch Intern Med. 2006; 166: 1805-1813
        • Palladini G.
        • Lavatelli F.
        • Russo S.
        • Perlini S.
        • Perfetti V.
        • Bosoni T.
        • Obici L.
        • Bradwell A.R.
        • D'Eril G.M.
        • Fogari R.
        • Moratti R.
        • Merlini G.
        Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL.
        Blood. 2006; 107: 3854-3858
        • Liu D.
        • Niemann M.
        • Hu K.
        • Herrmann S.
        • Stork S.
        • Knop S.
        • Ertl G.
        • Weidemann F.
        Echocardiographic evaluation of systolic and diastolic function in patients with cardiac amyloidosis.
        Am J Cardiol. 2015; 108: 591-598
        • Koyama J.
        • Ray-Sequin P.A.
        • Falk R.H.
        Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue doppler echocardiography in patients with al (primary) cardiac amyloidosis.
        Circulation. 2003; 107: 2446-2452
        • Kurt M.
        • Wang J.
        • Torre-Amione G.
        • Nagueh S.F.
        Left atrial function in diastolic heart failure.
        Circ Cardiovasc Imaging. 2009; 2: 10-15
        • 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 V, S.
        • 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
        • Kumar S.
        • Dispenzieri A.
        • Lacy M.Q.
        • Hayman S.R.
        • Buadi F.K.
        • Colby C.
        • Laumann K.
        • Zeldenrust S.R.
        • Leung N.
        • Dingli D.
        • Greipp P.R.
        • Lust J.A.
        • Russell S.J.
        • Kyle R.A.
        • Rajkumar V.
        • Gertz M.A.
        Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements.
        J Clin Oncol. 2012; 20: 989-995
        • Palladini G.
        • Dispenzieri A.
        • Gertz M.A.
        • Kumar S.
        • Wechalekar A.
        • Hawkins P.N.
        • Schonland S.
        • Hegenbart U.
        • Comenzo R.
        • Kastritis E.
        • Dimopoulos M.A.
        • Jaccard A.
        • Klersy C.
        • Merlini G.
        New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes.
        J Clin Oncol. 2012; 30: 4541-4549
        • 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.
        • Sezar 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.
        • Badano L.P.
        • Mor-Avi V.
        • Afilalo J.
        • Armstrong A.
        • Ernande L.
        • Flachskampf F.A.
        • Foster E.
        • Goldstein S.A.
        • Kuznetsova T.
        • Lancellotti P.
        • Muraru D.
        • Picard M.H.
        • Rietzschel E.R.
        • Rudski L.
        • Spencer K.T.
        • Tsang W.
        • Voigt J.U.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2015; 28 (e14): 1-39
        • Kobayashi Y.
        • Ariyama M.
        • Kobayashi Y.
        • Giraldeau G.
        • Fleischman D.
        • Kozelj M.
        • Vrtovec B.
        • Ashley E.
        • Kuznetsova T.
        • Schnittger I.
        • Liang D.
        • Haddad F.
        Comparison of left ventricular manual versus automates derived longitudinal strain: implications for clinical practice and research.
        Int J Cardiovasc Imaging. 2016; 32: 429-437
        • Kobayashi Y.
        • Moneghetti K.
        • Boralkar K.
        • Amsallem M.
        • Tuzovic M.
        • Liang D.
        • Yang P.
        • Narayan S.
        • Wu J.
        • Schnittger I.
        • Haddad F.
        Challenging the complementarity of different metrics of left atrial function: insight from a cardiomyopathy based study.
        Eur Hear J Cardiovasc Imaging. 2016;
        • Comenzo R.L.
        • Reece D.
        • Palladini G.
        • Seldin D.
        • Sanchorawala V.
        • Landau H.
        • Falk R.
        • Wells K.
        • Solomon A.
        • Wechalekar A.
        • Zonder J.
        • Dispenzieri A.
        • Gertz M.
        • Streicher H.
        • Skinner M.
        • Kyle R.A.
        • Merlini G.
        Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis.
        Leukemia. 2012; 26: 2317-2325
        • Lachmann H.J.
        • Gallimore R.
        • Gillmore J.D.
        • Carr-Smith H.D.
        • Bradwell A.R.
        • Pepys M.B.
        • Hawkins P.N.
        Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy.
        Br J Haematol. 2003; 122: 78-84
        • Nagueh S.F.
        • Smiseth O.A.
        • Appleton C.P.
        • Byrd 3rd, B.F.
        • Dokainish H.
        • Edvardsen T.
        • Flachskampf F.A.
        • Gillebert T.C.
        • Klein A.L.
        • Lancellotti P.
        • Marino P.
        • Oh J.K.
        • Popescu B.A.
        • Waggoner A.D.
        Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2016; 29: 277-314
        • Klein A.L.
        • Hatle L.K.
        • Burstow D.J.
        • Seward J.B.
        • Kyle R.A.
        • Bailey K.R.
        Doppler characterization of left ventricular diastolic function in cardiac amyloidosis.
        J Am Coll Cardiol. 1989; : 1017-1026
        • Liao R.
        • Jain M.
        • Teller P.
        • Connors L.H.
        • Ngoy S.
        • Skinner M.
        Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts.
        Circulation. 2001; 104: 1594-1597
        • Brenner D.A.
        • Jain M.
        • Pimentel D.R.
        • Wang B.
        • Connors L.H.
        • Skinner M.
        • Apstein C.S.
        • Liao R.
        Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in the cellular oxidant stress.
        Circ Res. 2004; 94: 1008-1010
        • Kristen A.V.
        • Brokbals E.
        • Aus dem Siepen F.
        • Bauer R.
        • Hein S.
        • Aurich M.
        • Riffel J.
        • Behrens H.M.
        • Kruger S.
        • Schirmacher P.
        • Katus H.A.
        • Rocken C.
        Cardiac amyloid load: a prognostic and predictive biomarker in patients with light-chain amyloidosis.
        J Am Coll Cardiol. 2016; 68: 13-24
        • Salinaro F.
        • Meier-Ewert H.K.
        • Miller E.J.
        • Pandey S.
        • Sanchorawala V.
        • Berk J.L.
        • Seldin D.C.
        • Ruberg F.L.
        Longitudinal systolic strain, cardiac function improvement, and survival following treatment of light-chain (AL) cardiac amyloidosis.
        Eur Hear J Cardiovasc Imaging. 2016;