JACC: CARDIOVASCULAR IMAGING, VOL. 7, NO. 10, 2014

Letters to the Editor

OCTOBER 2014:1062–8

CMR-Based Characterization of

the blood pool into the systemic interstitial space,

Cardiac Amyloidosis

which is extremely enlarged by light chain deposition (3–5); similar indexes of contrast kinetics might have

Amyloidosis is a systemic disease caused by the

been investigated in the study.

deposition of misfolded proteins. Cardiac involve-

Overall, CMR showed high diagnostic accuracy

ment is a major cause of morbidity and mortality,

in

especially in the light chain (AL) and transthyretin

contrast enhancement was present in all patients

(ATTR) forms. Amyloidosis usually presents as a

except 1 patient with AL amyloidosis with positive

restrictive cardiomyopathy with progressive systolic/

extracardiac biopsy and echocardiographic criteria

diastolic dysfunction and arrhythmias but is often

for cardiac involvement but no proven cardiac

misdiagnosed as hypertrophic or hypertensive heart

involvement by endomyocardial biopsy. Similarly,

disease.

12 patients with a negative final diagnosis at CMR

Recent evidence has supported the value of car-

detecting

showed

cardiac

positive

amyloidosis.

contrast

In

particular,

enhancement,

making

diac magnetic resonance (CMR) as a noninvasive

contrast enhancement 100% sensitive to detect car-

diagnostic tool to detect cardiac amyloidosis, which

diac amyloidosis. On the other hand, there were only

is characterized by marked myocardial interstitial

6 patients with false-positive results, who presented

expansion leading to a typical early and diffuse

cardiac

contrast enhancement. Dungu et al. (1) wrote an

enhancement at CMR but interstitial collagen accu-

interesting paper describing the differential CMR

mulation rather than amyloid deposition at endo-

characteristics according to the amyloid type (46 AL,

myocardial biopsy (3 hypertensive, 2 hypertrophic, 1

51 ATTR, 2 serum amyloid A, 1 apolipoprotein A-I).

alcoholic cardiomyopathy); a subtly different gado-

Cardiac amyloidosis was confirmed by endomyo-

linium kinetics (an earlier enhancement in amyloid-

hypertrophy

with

gadolinium

contrast

cardial biopsy in 50 patients, whereas the other 50

osis vs. a later enhancement in fibrosis) could have

patients had a positive extracardiac biopsy combined

been hypothetically disclosed by a careful analysis of

with echocardiographic criteria for cardiac amyloid-

gadolinium enhancement over time.

osis (2). Contrast enhancement was present in 99

We agree with the authors that the increased

patients, was more extensive in ATTR amyloidosis

availability of CMR has led to increased detection of

than in AL amyloidosis, and was incorporated into a

cardiac amyloidosis, superior tissue characterization,

scoring system (Query Amyloid Late Enhancement)

and possible differentiation between interstitial dis-

that independently differentiated ATTR amyloidosis

eases (inflammation, fibrosis, amyloid). The different

from AL amyloidosis. Despite poorer left ventricular

biochemical properties of amyloid subtypes likely

systolic function and worse biventricular hypertro-

explain not only the variable imaging features but

phy, patients with ATTR amyloidosis experienced a

also the distinct prognosis. Further studies are

better outcome than did those with AL amyloidosis.

needed to expand the results of the present study,

Nevertheless, the study did not examine all

possibly investigating the complexity of cardiac in-

possible parameters provided by a standard CMR

terstitial remodeling with novel T1 mapping tech-

scan. Right ventricular volumes, mass, and ejection

niques and correlating CMR findings with established

fraction, which provide a more detailed character-

biohumoral (natriuretic peptides, troponins), func-

ization of right ventricular morphology and function

tional (peak oxygen consumption), electrocardio-

than right ventricular wall thickness alone, were not

graphic, and echocardiographic parameters.

measured.

Moreover,

the

Query

Amyloid

Late

Enhancement score did not include contrast enhancement of the atrial chambers, which is a common finding in patients with cardiac amyloidosis

Andrea Barison, MD, PhD* Pier Giorgio Masci, MD, PhD Giovanni Donato Aquaro, MD

and in this study resulted in a difference between

*Fondazione “G.Monasterio” CNR-Regione Toscana

patients with ATTR amyloidosis and patients with

Via Moruzzi, 1

AL amyloidosis. Finally, gadolinium kinetics in the

56124 Pisa

myocardium and in the blood pool is significantly

Italy

deranged in amyloid patients, but it was not taken

E-mail: [email protected]

into account when comparing patients with AL

http://dx.doi.org/10.1016/j.jcmg.2014.04.020

amyloidosis and patients with ATTR amyloidosis. As an example, blood pool early darkening after contrast administration is a typical feature of AL amyloidosis due to the rapid contrast washout from

REFERENCES 1. Dungu JN, Valencia O, Pinney JH, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. J Am Coll Cardiol Img 2014;7:133–42.

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JACC: CARDIOVASCULAR IMAGING, VOL. 7, NO. 10, 2014

Letters to the Editor

OCTOBER 2014:1062–8

2. Gertz MA, Comenzo R, Falk RH, et al. 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;

type. The thinness of the atrial chambers precludes

79:319–28.

kinetics, already widely reported in cardiac amyloi-

3. Maceira AM, Joshi J, Prasad SK, et al. Cardiovascular magnetic resonance

dosis, appear very similar between amyloid types (4),

in cardiac amyloidosis. Circulation 2005;111:186–93.

but further quantitative assessment in this multiple

4. Emdin M, Aquaro GD, Pugliese NR, et al. Myocardial gadolinium kinetics evaluation at magnetic resonance imaging for the diagnosis of cardiac amyloidosis (abstr). J Am Coll Cardiol 2013;61(10_S). http://dx.doi.org/10. 1016/S0735-1097(13)61237-1.

center, multiple protocol study was not feasible.

5. Aquaro GD, Pugliese NR, Perfetto F, et al. Myocardial signal intensity decay after gadolinium injection: a fast and effective method for the diagnosis of cardiac amyloidosis. Int J Cardiovasc Imaging 2014;30:1105–15.

the view that our findings were actually strengthened

their use as a reliable measurement when assessing late gadolinium enhancement. Altered gadolinium

Overall, the comments highlight the limitations of any retrospective study, but we would like to reinforce by the study design. The data were derived from nonstandardized protocols performed on various scanners; however, despite this, an obvious difference between the amyloid subtypes was shown. Our results

REPLY: CMR-Based Characterization of

are therefore relevant to nonspecialist CMR centers,

Cardiac Amyloidosis

which often raise the possibility of amyloidosis for the

We thank Barison et al. for their interest in our paper (1). Cardiac amyloidosis is gaining significant exposure in the cardiac magnetic resonance (CMR) community because of the characteristic and near pathognomonic findings with the technique. We reported the first study that specifically aimed to differentiate between the light chain (AL) and transthyretin (ATTR) subtypes of amyloidosis through retrospective analysis of studies performed in multiple hospitals referring to a specialist amyloidosis center (1). We did not include right ventricular volumes, mass, and ejection fraction in the analyses because not all studies included sufficient images to perform accurate analysis. Right ventricular morphology data (particularly right ventricular mass) are less reproducible, even in single center studies (2), and in this series axial data sets had rarely been routinely obtained (3). The Query Amyloid Late Enhancement score, a novel late gadolinium enhancement analysis, was designed to be a simple add-on to standard reporting. Various versions of the Query Amyloid Late

Enhancement

score

were

devised,

incor-

porating other CMR variables, but we and the reviewers decided to report the score independently, without including potentially confounding factors, because it was a standalone predictor of amyloid

clinicians who refer patients for CMR. Prospective studies with specialist amyloid protocols may seem ideal; however, in the real world, our results are applicable to all CMR operators. Jason N. Dungu, MBBS, BSc* Lisa J. Anderson, MD *St George’s University of London Cranmer Terrace London SW17 0RE England E-mail: [email protected] http://dx.doi.org/10.1016/j.jcmg.2014.04.021 Please note: Dr. Dungu was supported by British Heart Foundation Clinical Research Training Fellowship grant no. FS/09/063/28026. Dr. Anderson has reported that she has no relationships relevant to the contents of this paper to disclose.

REFERENCES 1. Dungu JN, Valencia O, Pinney JH, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. J Am Coll Cardiol Img 2014;7:133–42. 2. Mooij CF, de Wit CJ, Graham DA, Powell AJ, Geva T. Reproducibility of MRI measurements of right ventricular size and function in patients with normal and dilated ventricles. J Magn Reson Imaging 2008;28:67–73. 3. Clarke CJ, Gurka MJ, Norton PT, Kramer CM, Hoyer AW. Assessment of the accuracy and reproducibility of RV volume measurements by CMR in congenital heart disease. J Am Coll Cardiol Img 2012;5:28–37. 4. Dungu JN, Anderson LJ, Whelan CJ, Hawkins PN. Cardiac transthyretin amyloidosis. Heart 2012;98:1546–54.