Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis.

OBJECTIVES: Our aim was to evaluate the role and mechanism of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in identifying cardiac amyloidosis (CA) and to investigate associations between LGE and clinical, morphologic, functional, and biochemical features.

BACKGROUND: CA can be challenging to diagnose by echocardiography. Recent studies have demonstrated an emerging role for LGE-CMR.

METHODS: LGE-CMR was performed in 120 patients with amyloidosis. Cardiac histology was available in 35 patients. The remaining 85 patients were divided into those with and without echocardiographic evidence of CA.

RESULTS: Of the 35 patients with histologically verified CA, abnormal LGE was present in 34 (97%) patients and increased echocardiographic left ventricular wall thickness in 32 (91%) patients. Global transmural or subendocardial LGE (83%) was most common and was associated with greater interstitial amyloid deposition (p = 0.03). Suboptimal myocardial nulling (8%) and patchy focal LGE (6%) were also observed. LGE distribution matched the deposition pattern of interstitial amyloid. Among patients without cardiac histology, LGE was present in 86% of those with evidence of CA by echocardiography and in 47% of those without evidence of CA by echocardiography. In patients without echocardiographic evidence of CA, the presence of LGE was associated with worse clinical, electrocardiographic (ECG), and cardiac biomarker profiles. In all patients, LGE presence and pattern was associated with New York Heart Association functional class, ECG voltage, left ventricular mass index, right ventricular wall thickness, troponin-T, and B-type natriuretic peptide levels.

CONCLUSIONS: LGE is common in CA and detects interstitial expansion from amyloid deposition. Global transmural or subendocardial LGE is most common, but suboptimal myocardial nulling and focal patchy LGE are also observed. LGE-CMR may detect early cardiac abnormalities in patients with amyloidosis with normal left ventricular thickness. The presence and pattern of LGE is strongly associated with clinical, morphologic, functional, and biochemical markers of prognosis. 

PMID: 20159642

Posted in * Journal Club Selections, Magnetic Resonance Imaging.


  1. What was the objective of this investigation?
    To evaluate the role and mechanism of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) in identifying cardiac amyloidosis (CA); also to investigate the associations b/w LGE and clinical/morphologic/functional/and biochemical features

    What were inclusion/exclusion criteria?
    Patients with documented amyloidosis referred for CMR between Jan 2006 and Dec 2007 were screened for inclusion. CMR was performed at discretion of attending physician. Inclusion criteria included histologically proven amyloidosis, confirmatory evidence of monoclonal protein in serum or urine and or monoclonal plasma cells in the bone marrow. Patients with prior MI/myocarditis/prior peripheral blood stem cell Tx/or heart Tx were excluded.

    How was cardiac involvement defined? How were sub groups defined?
    Mean LV thickness of IVS and lateral wall > 12 mm on echo was taken as evidence of cardiac involvement. Patients were then divided into 3 groups: those with positive cardiac histology for CA (35), those without cardiac histology but with echocardiographic evidence of CA (49), and those without histology and no echo evidence of CA (36).

    How were histologic samples obtained?
    35 patients had cardiac histology; 33 of these were obtained by endomyocardial biopsy with 3-5 specimens of the RV. LV tissue was available in 5 patients (4 by autopsy, 1 explanted), with multiple samples from a mid level section. The extent of interstitial amyloid was graded semiquantitatively, as was vascular involvement. Immunohistochemical staining was performed to assess specific components (eg transthyretin) of the amyloid.

    What echocardiographic assessment was included? Does this raise any issues?
    Left ventricle thickness was recorded from parasternal long axis view (mean of septal and posterior walls). However, diastology was not assessed, and no strain imaging was performed, both of which may have helped better define CA. Also, thickness of LV could easily be confounded by patients with hypertension or infiltrative process other than amyloid.

    What did the CMR protocol consist of? Were there any possible limitations attributable to this?
    LGE was performed 7-12 m after administration of gadolinium. TI was optimized by use of multi-TI cine fast gradient echo sequence. As some other investigators have suggested, and the current authors noted, an alternate approach is to perform LGE imaging earlier (4-7 m range), as patients with diffuse amyloidosis have dramatically altered gadolinium kinetics. Imaging at 10-12 m could potentially lead to missing the dynamic post contrast changes noted with cardiac amyloidosis. The authors contention is that use of a more consistent approach is important when CA is not suspected.

    What were the imaging findings of patients with positive histology?
    Echocardiographic wall thickness was increased in 32/35 (91%) biopsy confirmed cases. LGE was present in 34/35 (97%); this was global and transmural in 21 (60%) of cases, global subendocardial in 8 (23%), and patchy focal in 2 (6%). In 3 (8%) of cases there was suboptimal nulling (SN) where adequately nulled images could not be obtained. Of the 3 patients with normal echo wall thickness but positive histology, 2 had LGE ( 1 global, 1 SN). Global transmural or subendocardial LGE was associated with greater amyloid deposition in RV. The one pt. without LGE and positive histology had mild amount of amyloid on tissue sample.

    Was there any correlation b/w histologic type of amyloid and pattern of LGE?
    No (p = 0.73)

    Was there any transmyocardial difference in amyloid deposition in LV samples?
    No – which is contrary to reported results from another investigator (Maceira et al). 1/5 did have patchy focal deposits corresponding to LGE.

    What were findings of patients without histology?
    85 pts – 49 of which were positive by echo criteria. 42 (86%) of these had LGE on CMR. Those with LGE had greater LV and RV wall thickness, lower LVEF, and trend toward greater symptoms.
    The remaining 36 pts without echocardiographic evidence of cardiac involvement were notable for 17 (47%) with LGE (8% global subendocardial, 17% SN, PF in 22%).

    What are some takeaway points from this investigation?
    – High sensitivity (97%) of LGE was noted in patients with positive cardiac histology. The one patient with positive biopsy but negative LGE suggests a threshold required to detect the amyloid infiltration with conventional IR post contrast imaging.
    – In this group of patients, global transmural or subendocardial LGE was associated with the greatest amyloid deposition and the worst clinical morphologic, functional, and biomarker profile. This also suggests prognostic significance of LGE (as NYHA functional class, LV thickness, LVEF, Troponin-T, and BNP have been shown to have prognostic value).
    – Reiteration of the causative role of amyloid infiltration leading to interstitial expansion and therefore LGE was noted. Interstitial fibrosis secondary to amyloid vascular involvement was not noted.
    – SN and PF LGE were associated with lesser degrees of amyloid deposition
    – A substantial proportion of patients with normal LV thickness by echocardiography were noted to have LGE, suggesting that CMR may allow early characterization of cardiac amyloidosis. This may have treatment implications, for example in pts with AL amyloid.

  2. What was the objective of this investigation?
    The objective of this study, in our opinion, was very mechanistic and prognostic which made it very interesting from the clinical point of view. The aim of the study is to investigate the role of late gadolinium enhancement in cardiac amyloidosis.

    What echocardiographic assessment was included?
    We felt that the echocardiographic assessment lacked some functional analysis, specifically diastolic function measurements. Approximately one-half of the patients (47%) with normal LV thickness (one of the echo parameters used for determining the presence of amyloid) without cardiac biopsy had LGE. If the number of patients classified as having no evidence of amyloid by echo had been assessed for diastolic dysfunction, this number would probably be much different with many more patients grouped as having echocardiographic evidence of amyloid in virtue of the presence of diastolic dysfunction.

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