Author + information
- Frederick L. Ruberg, MD∗ (, )
- Marianna Fontana, MD and
- Julian D. Gillmore, MD, PhD
- ↵∗Amyloidosis Center and Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, 88 East Newton Street, Boston, Massachusetts 02118
We read with interest the report of Kristen et al. (1), in which the prognostic usefulness of histologic amyloid load quantification by endomyocardial biopsy was described. Although the investigators stated that no significant variation was observed between biopsy sites, this observation was not quantified. Our collective experience is that Congo red staining of different biopsy specimens from within the same organ in the same patient can vary greatly in the so-called amyloid load, reflecting the patchy nature of amyloid deposition, which is well described (2) and introduces the likelihood of sampling error. Furthermore, quantification of amyloid load from a single slide does not control for variation in sample size, because a true load would require normalization to total heart size as determined by myocardial mass. In addition, immunohistochemistry in light-chain (AL) amyloidosis is associated with both false negative and considerable background nonspecific staining, which potentially confounds quantification of amyloid burden by the method described. Because the investigators found no survival advantage with chemotherapy in AL amyloidosis in the context of higher levels of amyloid load (>20%), we are concerned that clinicians may choose to withhold life-extending chemotherapy treatment from patients with advanced cardiac AL amyloidosis because of perceived futility, when it remains clear that some such patients do undoubtedly benefit from it. Cardiac magnetic resonance (CMR) with extra cellular volume (ECV) determination is an attractive noninvasive modality that can be used to quantify amyloid burden because the entire heart is imaged, yielding a truer average that has been shown to strongly correlate with cardiac specific biomarkers such as N-terminal pro−brain natriuretic peptide (3). Importantly, CMR with ECV measurement also lends itself readily to repeat measurements, does not have the attendant risks of an invasive procedure, and is likely to afford a more sensitive means to follow amyloid regression with treatment (4). We agree with the investigators that precursor protein identification is an essential step in the management of cardiac amyloid patients, and that endomyocardial biopsy has a definite role both in diagnosis and typing of cardiac amyloid. However, we would strongly suggest that caution must be exercised when making management decisions based upon quantification of amyloid from a histological specimen.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Kristen A.V.,
- Brokbals E.,
- Aus dem Siepen F.,
- et al.
- Fontana M.,
- Pica S.,
- Reant P.,
- et al.
- ↵Martinez-Naharro A KD, Treibel TA, Abdel-Gadir A, et al. Regression of cardiac AL amyloidosis demonstrated by cardiovascular magnetic resonance: a new era of understanding. Paper Presented at: XVth International Symposium on Amyloidosis; July 3-7, 2016; Uppsala, Sweden.