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Cardiac amyloidosis: in search of the ideal diagnostic tool

  • Sophie I. MavrogeniEmail author
  • Vasiliki Vartela
  • Argyrios Ntalianis
  • Rosa Vretou
  • Ignatios Ikonomidis
  • Marini Tselegkidou
  • Ioannis Paraskevaidis
  • George Markousis-Mavrogenis
  • Michel Noutsias
  • Angelos Rigopoulos
  • Genovefa Kolovou
  • Efstathios Kastritis
Review articles

Abstract

Background

Cardiac amyloidosis (CA) is due to amyloid deposition in the myocardium. Transthyretin (ATTR) and light-chain (AL) amyloidosis are the main types of CA. Here, we present the clinical and imaging findings in patients with CA and discuss the controversies with the aim of finding the ideal diagnostic tool.

Methods

Ten patients suspected of having CA on the basis of electrocardiographic (ECG) and echocardiographic findings were evaluated via cardiovascular magnetic resonance imaging (CMR; 1.5 T) using cine, late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction. N‑terminal pro-B-type natriuretic peptide (NT-proBNP) levels were also assessed in all patients.

Results

All ten patients had an echocardiogram suggestive of CA. The CMR study documented ventricular hypertrophy leading to small ventricular volumes, as assessed by echocardiography. Diffuse subendocardial LGE, supporting the diagnosis of CA, was identified in all except one patient, who had subepicardial LGE due to myocarditis that was verified by endomyocardial biopsy (EMB). Right ventricular (RV) involvement was identified in four of the ten patients, whose condition deteriorated rapidly over the next 6 months. The NT-proBNP levels were >332 pg/ml in all except two patients. Light-chain amyloidosis was identified via fat tissue biopsy in two patients and through renal biopsy in one patient. In two patients with positive technetium-99m, EMB confirmed the diagnosis of ATTR.

Conclusion

NT-proBNP may be a sensitive but nonspecific biomarker for assessing CA. However, CMR is the only imaging modality that can assess the pathophysiologic background of cardiac hypertrophy and the severity of CA, irrespective of NT-proBNP level.

Keywords

Cardiac amyloidosis Cardiovascular magnetic resonance imaging N‑terminal pro-BNP Electrocardiography Echocardiography 

Abbreviations

CA

Cardiac amyloidosis

CMR

Cardiovascular magnetic resonance

ECG

Electrocardiogram

ECV

Extracellular volume fraction

LGE

Late gadolinium enhancement

LVEF

Left ventricular ejection fraction

RVEF

Right ventricular ejection fraction

Kardiale Amyloidose: Suche nach dem idealen diagnostischen Verfahren

Zusammenfassung

Hintergrund

Der kardialen Amyloidose (CA) liegt eine Amyloidablagerung im Myokard zugrunde. Transthyretin- (ATTR) und Leichtketten(AL)-Amyloidose sind die Hauptursachen der CA. Ziel der Autoren war es, klinische und bildgebende Befunde bei Patienten mit CA zu präsentieren und die entsprechenden Kontroversen mit dem Ziel darzustellen, das ideale Diagnoseinstrument zu erkennen.

Methoden

Es wurden 10 Patienten, bei denen die Verdachtsdiagnose CA aufgrund von Elektrokardiogramm (EKG) und Echokardiographie bestand, mittels kardiovaskulärer Magnetresonanzbildgebung (CMR; 1,5 T) mit Cine-Funktion, Beurteilung des Late Gadolinium Enhancement (LGE), T1-, T2-Mapping und Bestimmung der extrazellulären Volumenfraktion untersucht. Der Wert für NT-proBNP („N-terminal pro-B-type natriuretic peptide“) wurde ebenfalls bei allen gemessen.

Ergebnisse

Bei allen (n = 10) Patienten gab es in der Echokardiographie Hinweise auf CA. In der CMR wurde eine ventrikuläre Hypertrophie dokumentiert, die zu kleinen ventrikulären Volumina führte, was durch die Echokardiographie festgestellt wurde. Diffuses subendokardiales LGE, das für die Diagnose einer CA spricht, wurde bei allen mit Ausnahme eines Patienten, der subepikardiales LGE aufgrund einer Myokarditis aufwies, durch eine Endomyokardbiopsie (EMB) bestätigt. Eine rechtsventrikuläre (RV-)Beteiligung wurde bei 4/10 Patienten festgestellt, deren Zustand sich innerhalb der nächsten 6 Monate rasch verschlechterte. Der NT-proBNP-Spiegel war insgesamt >332 pg/ml, mit Ausnahme von 2 Patienten. Eine AL-Amyloidose wurde durch Fettgewebebiopsie bei 2/10 und durch Nierenbiopsie bei 1/10 Patienten identifiziert. Bei 2/10 Patienten mit positiver 99mTc-Szintigraphie wurde die Diagnose einer ATTR-Amyloidose durch die EMB bestätigt.

Schlussfolgerung

NT-proBNP ist möglicherweise ein sensitiver, aber nicht spezifischer Biomarker für die Beurteilung einer CA. Die CMR ist jedoch das einzige Bildgebungsverfahren, mit dem der pathophysiologische Hintergrund der Herzhypertrophie und der Schweregrad der CA unabhängig von den NT-proBNP-Spiegeln beurteilt werden kann.

Schlüsselwörter

Kardiale Amyloidose Kardiovaskuläre Magnetresonanztomographie N‑terminales proBNP Elektrokardiogramm Echokardiographie 

Notes

Author Contribution

All authors read and approved the final manuscript. S.M: CMR scanning evaluation and manuscript writing; VV: Echo assessment and writing; A.N: Cardiac data assessment and writing; RV: Cardiac, echo and nuclear data assessment and writing; I.I: Cardiac data assessment and writing; MT: Biopsy data assessment and writing; E.K: Biopsy assessment; I.P: Coordination of echo assessment, manuscript writing; G.M.M: CMR image analysis and manuscript writing; M.N: Coordination of manuscript writing; G.K: Coordination of manuscript writing.

Compliance with ethical guidelines

Conflict of interest

S.I. Mavrogeni, V. Vartela, A. Ntalianis, R. Vretou, I. Ikonomidis, M. Tselegkidou, I. Paraskevaidis, G. Markousis-Mavrogenis, M. Noutsias, A. Rigopoulos, G. Kolovou and E. Kastritis declare that they have no competing interests.

All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards and have been approved by the Onassis Cardiac Surgery Center ethics committee. Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S et al (2007) A primer of amyloid nomenclature. Amyloid 14(3):179–183CrossRefGoogle Scholar
  2. 2.
    Buxbaum JN (2004) The systemic amyloidoses. Curr Opin Rheumatol 16(1):67–75CrossRefGoogle Scholar
  3. 3.
    Mohammed SF, Mirzoyev SA, Edwards WD et al (2014) Left ventricular amyloi deposition in patients with heart failure and preserved ejection fraction. Jacc Heart Fail 2(2):113–122CrossRefGoogle Scholar
  4. 4.
    Java AP, Greason KL, Dispenzieri A, Grogan M, King KS, Maleszewski JJ, Daly RC, Eleid MF, Pochettino A, Schaff HV (2018) Aortic valve replacement in patients with amyloidosis. J Thorac Cardiovasc Surg 156(1):98–103CrossRefGoogle Scholar
  5. 5.
    Maurer MS (2015) Noninvasive identification of ATTRwt cardiac amyloid: the re-emergence of nuclear cardiology. Am J Med 128(12):1275–1280CrossRefGoogle Scholar
  6. 6.
    Quarta CC, Buxbaum JN, Shah AM et al (2015) The amyloidogenic V122I transthyretin variant in elderly black Americans. N Engl J Med 372(1):21–29CrossRefGoogle Scholar
  7. 7.
    Rapezzi C, Lorenzini M, Longhi S et al (2015) Cardiac amyloidosis: the great pretender. Heart Fail Rev 20(2):117–124CrossRefGoogle Scholar
  8. 8.
    Westphal JG, Rigopoulos AG, Bakogiannis C, Ludwig SE, Mavrogeni S, Bigalke B, Doenst T, Pauschinger M, Tschope C, Schulze PC, Noutsias M (2017) The MOGE(S) classification for cardiomyopathies: current status and future outlook. Heart Fail Rev 22((6):743–752CrossRefGoogle Scholar
  9. 9.
    Bokhari S, Castaρo A, Pozniakoff T et al (2013) 99mTc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging 6(2):195–201CrossRefGoogle Scholar
  10. 10.
    Maurer MS, Grogan DR, Judge DP et al (2015) Tafamidis in transthyretin amyloid cardiomyopathy: effects on transthyretin stabilization and clinical outcomes. Circ Heart Fail 8(3:519–526CrossRefGoogle Scholar
  11. 11.
    Noutsias M, Seeberg B, Schultheiss HP, Kühl U (1999) Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation 99(16):2124–2131CrossRefGoogle Scholar
  12. 12.
    Cheng Z, Zhu K, Tian Z, Zhao D, Cui Q, Fang Q (2013) The findings of electro-cardiography in patients with cardiac amyloidosis. Ann Noninvasive Electrocardiol 18(2):157–162CrossRefGoogle Scholar
  13. 13.
    Ton V, Mukherjee M, Judge DP (2014) Transthyretin cardiac amyloidosis: pathogenesis, treatments, and emerging role in heart failure with preserved ejection fraction. Clin Med Insights Cardiol 8(Suppl 1):39–44PubMedGoogle Scholar
  14. 14.
    Ruberg FL, Transthyretin BJL (2012) (TTR) cardiac amyloidosis. Circulation 126(10):1286–1300CrossRefGoogle Scholar
  15. 15.
    Gertz MA, Benson MD, Dyck PJ, Grogan M, Coelho T, Cruz M et al (2015) Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol 66(21):2451–2466CrossRefGoogle Scholar
  16. 16.
    Grogan M, Dispenzieri A, Gertz MA (2017) Light-chain cardiac amyloidosis: strategies to promote early diagnosis and cardiac response. Heart 103(14):1065–1072CrossRefGoogle Scholar
  17. 17.
    Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B et al (2012) AL amyloidosis. Orphanet Journal of Rare Diseases 7:54CrossRefGoogle Scholar
  18. 18.
    Mollee P, Renaut P, Gottlieb D, Goodman H (2014) How to diagnose amyloidosis. Intern Med J 44(1):7–17CrossRefGoogle Scholar
  19. 19.
    Sanchorawala V (2006) Light-chain (AL) amyloidosis: diagnosis and treatment. Clin J Am Soc Nephrol 1(6):1331–1341CrossRefGoogle Scholar
  20. 20.
    Marcoux J, Mangione PP, Porcari R, Degiacomi MT, Verona G, Taylor GW et al (2015) A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis. EMBO Mol Med 7(10):1337–1349CrossRefGoogle Scholar
  21. 21.
    Loo D, Mollee PN, Renaut P, Hill MM (2011) Proteomics in molecular diagnosis: typing of amyloidosis. J Biomed Biotechnol 2011:754109CrossRefGoogle Scholar
  22. 22.
    Karamitsos TD, Piechnik SK, Banypersad SM, Fontana M, Ntusi NB, Ferreira VM et al (2013) Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. JACC Cardiovasc Imaging 6:488–497CrossRefGoogle Scholar
  23. 23.
    Fontana M, Banypersad SM, Treibel TA, Maestrini V, Sado DM, White SK et al (2014) Native T1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging 7(2):157–165CrossRefGoogle Scholar
  24. 24.
    Banypersad SM, Sado DM, Flett AS, Gibbs SDJ, Pinney JH, Maestrini V et al (2013) Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging 6:34–39CrossRefGoogle Scholar
  25. 25.
    Fontana M, Pica S, Reant P, Abdel-Gadir A, Treibel TA, Banypersad SM et al (2015) Prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 132:1570–1579CrossRefGoogle Scholar
  26. 26.
    Fontana M, Banypersad SM, Treibel TA, Abdel-Gadir A, Maestrini V, Lane T et al (2015) Differential myocyte responses in patients with cardiac transthyretin amyloidosis and light-chain amyloidosis: a cardiac MR imaging study. Radiology 277:388–397CrossRefGoogle Scholar
  27. 27.
    Treibel TA, Fontana M, Gilbertson JA, Castelletti S, White SK, Scully PR et al (2016) Occult transthyretin cardiac amyloid in severe calcific aortic stenosis: prevalence and prognosis in patients undergoing surgical aortic valve replacement. Circ Cardiovasc Imaging 9(8):eoo5066CrossRefGoogle Scholar
  28. 28.
    Messroghli DR, Moon JC, Ferreira VM, Grosse-Wortmann L, He T, Kellman P, Mascherbauer J, Nezafat R, Salerno M, Schelbert EB, Taylor AJ, Thompson R, Ugander M, van Heeswijk RB, Friedrich MG (2017) Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: a consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). J Cardiovasc Magn Reson 19(1):75CrossRefGoogle Scholar
  29. 29.
    Lin L, Li X, Feng J, Shen KN, Tian Z, Sun J, Mao YY, Cao J, Jin ZY, Li J, Selvanayagam JB, Wang YN (2018) The prognostic value of T1 mapping and late gadolinium enhancement cardiovascular magnetic resonance imaging in patients with light chain amyloidosis. J Cardiovasc Magn Reson 20(1):2CrossRefGoogle Scholar
  30. 30.
    Wan K, Sun J, Han Y, Luo Y, Liu H, Yang D, Cheng W, Zhang Q, Zeng Z, Chen Y (2018) Right ventricular involvement evaluated by cardiac magnetic resonance imaging predicts mortality in patients with light chain amyloidosis. Heart Vessels 33(2):170–179CrossRefGoogle Scholar
  31. 31.
    Porciani MC, Lilli A, Perfetto F, Cappelli F, Massimiliano Rao C, Del Pace S et al (2009) Tissue Doppler and strain imaging: a new tool for early detection of cardiac amyloidosis. Amyloid 16:63–70CrossRefGoogle Scholar
  32. 32.
    Koyama J, Ray-Sequin PA, Falk RH (2003) Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 107:2446–2452CrossRefGoogle Scholar
  33. 33.
    Baccouche H, Maunz M, Beck T, Gaa E, Banzhaf M, Knayer U et al (2012) Differentiating cardiac amyloidosis and hypertrophic cardiomyopathy by use of three-dimensional speckle tracking echocardiography. Echocardiography 29:668–677CrossRefGoogle Scholar
  34. 34.
    Kotecha T, Martinez-Naharro A, Treibel TA, Francis R, Nordin S, Abdel-Gadir A, Knight DS, Zumbo G, Rosmini S et al (2017) Multiparametric mapping to understand pathophysiology in cardiac amyloidosis. Heart 103(Suppl 1):A1–A25CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • Sophie I. Mavrogeni
    • 1
    Email author
  • Vasiliki Vartela
    • 1
  • Argyrios Ntalianis
    • 2
  • Rosa Vretou
    • 3
  • Ignatios Ikonomidis
    • 3
  • Marini Tselegkidou
    • 2
  • Ioannis Paraskevaidis
    • 2
  • George Markousis-Mavrogenis
    • 1
  • Michel Noutsias
    • 4
  • Angelos Rigopoulos
    • 4
  • Genovefa Kolovou
    • 1
  • Efstathios Kastritis
    • 2
  1. 1.Onassis Cardiac Surgery CenterAthensGreece
  2. 2.Alexandra’s HospitalAthensGreece
  3. 3.Attikon HospitalAthensGreece
  4. 4.Mid-German Heart Center, Department of Internal Medicine III (KIM-III), Division of Cardiology, Angiology and Intensive Medical Care, University Hospital HalleMartin-Luther-University HalleHalle (Saale)Germany

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