Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis
Thomas A Treibel, Steve Bandula, Marianna Fontana, Steven K White, Janet A Gilbertson, Anna S Herrey, Julian D Gillmore, Shonit Punwani, Philip N Hawkins, Stuart A Taylor, James C Moon, Thomas A Treibel, Steve Bandula, Marianna Fontana, Steven K White, Janet A Gilbertson, Anna S Herrey, Julian D Gillmore, Shonit Punwani, Philip N Hawkins, Stuart A Taylor, James C Moon
Abstract
Background: Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed.
Objectives: To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT.
Methods: Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area).
Results: ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001).
Conclusion: Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis.
Keywords: Amyloidosis; CCT; CMR; Cardiac imaging techniques; Extracellular space.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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References
- Banypersad S.M., Moon J.C., Whelan C., Hawkins P.N., Wechalekar A.D. Updates in cardiac amyloidosis: a review. J Am Heart Assoc. 2012;1:e000364.
- Merlini G., Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583–596.
- Ng B., Connors L.H., Davidoff R., Skinner M., Falk R.H. Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med. 2005;165:1425–1429.
- Dubrey S.W., Cha K., Skinner M., LaValley M., Falk R.H. Familial and primary (al) cardiac amyloidosis: Echocardiographically similar diseases with distinctly different clinical outcomes. Heart. 1997;78:74–82.
- Rapezzi C., Merlini G., Quarta C.C. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120:1203–1212.
- Hanna M. Novel drugs targeting transthyretin amyloidosis. Curr Heart Fail Rep. 2014 Mar;11(1):50–57.
- Wechalekar A.D., Hawkins P.N. Al amyloidosis: new drugs and tests, but old challenges. Oncology (Williston Park) 2012;26 161–162, 164.
- Syed I.S., Glockner J.F., Feng D. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging. 2010;3:155–164.
- Pinney J.H., Whelan C.J., Petrie A. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2:e000098.
- Perugini E., Guidalotti P.L., Salvi F. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mtc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005;46:1076–1084.
- Hutt D.F., Quigley A.M., Page J. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging. 2014
- Maceira A.M., Prasad S.K., Hawkins P.N., Roughton M., Pennell D.J. Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis. J Cardiovasc Magn Reson. 2008;10:54.
- Banypersad S.M., Sado D.M., Flett A.S. Quantification of myocardial extracellular volume fraction in systemic al amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging. 2013;6:34–39.
- Bandula S., White S.K., Flett A.S. Measurement of myocardial extracellular volume fraction by using equilibrium contrast-enhanced ct: validation against histologic findings. Radiology. 2013;269:396–403.
- Nacif M.S., Kawel N., Lee J.J. Interstitial myocardial fibrosis assessed as extracellular volume fraction with low-radiation-dose cardiac ct. Radiology. 2012;264:876–883.
- Nacif M.S., Liu Y., Yao J. 3d left ventricular extracellular volume fraction by low-radiation dose cardiac ct: assessment of interstitial myocardial fibrosis. J Cardiovasc Comput Tomogr. 2013;7:51–57.
- Nagueh S.F., Appleton C.P., Gillebert T.C. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10:165–193.
- Gertz M.A., Comenzo R., Falk R.H. 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.
- Fontana M., Banypersad S.M., Treibel T.A. Native t1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging. 2014;7:157–165.
- Hausleiter J., Meyer T., Hermann F. Estimated radiation dose associated with cardiac ct angiography. Jama. 2009;301:500–507.
- Piechnik S.K., Ferreira V.M., Dall'Armellina E. Shortened modified look-locker inversion recovery (shmolli) for clinical myocardial t1-mapping at 1.5 and 3 t within a 9 heartbeat breathhold. J Cardiovasc Magn Reson. 2010;12:69.
- Flett A.S., Hayward M.P., Ashworth M.T. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122:138–144.
- Moon J.C., Messroghli D.R., Kellman P. Myocardial t1 mapping and extracellular volume quantification: a society for cardiovascular magnetic resonance (scmr) and cmr working group of the european society of cardiology consensus statement. J Cardiovasc Magn Reson. 2013;15:92.
- Sado D.M., Flett A.S., Banypersad S.M. Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart. 2012;98:1436–1441.
- Kuruvilla S., Janardhanan R., Antkowiak P. Increased extracellular volume and altered mechanics are associated with lvh in hypertensive heart disease, not hypertension alone. JACC Cardiovasc Imaging. 2015;8:172–180.
- Brouwer W.P., Baars E.N., Germans T. In-vivo t1 cardiovascular magnetic resonance study of diffuse myocardial fibrosis in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson. 2014;16:28.
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