How to Diagnose ATTR Cardiac Amyloidosis
March 1, 2023 4 minutes read
By Michael H. Crawford, MD, Editor
SYNOPSIS: A retrospective study of patients with confirmed cardiac amyloidosis showed negative light chain biomarkers and a typical pattern of cardiac amyloid on cardiac MRI was highly specific for the diagnosis of the transthyretin subtype and may obviate the need for further testing before starting treatment.
SOURCE: Slivnick JA, Alvi N, Singulane CC, et al. Non-invasive diagnosis of transthyretin cardiac amyloidosis utilizing typical late gadolinium enhancement pattern on cardiac magnetic resonance and light chains. Eur Heart J Cardiovasc Imaging 2023; Jan 10: jeac249. doi: 10.1093/ehjci/jeac249. [Online ahead of print].
When it comes to cardiac amyloidosis (CA) caused by the deposition of immunoglobulin light chain (AL) or transthyretin (ATTR) proteins, consider how treatment is different. This means it is important to identify the subtype of CA. One could use cardiac MRI to diagnose CA, but can it differentiate AL from ATTR CA? Slivnick et al hypothesized including serum light chain biomarkers with cardiac MRI may provide an accurate diagnosis of the CA subtype.
To test this hypothesis, they retrospectively evaluated patients at three medical centers with confirmed ATTR or AL CA (2011 to 2021). Patients exhibited the typical findings of CA on cardiac MRI. Subendocardial or transmural late gadolinium enhancement and the Look-Locker sequence was used to identify the optimal nulling point of normal myocardium. Researchers confirmed CA subtype using a combination of biopsy, technetium pyrophosphate (PYP) nuclear scan, and kappa/lambda light chain biomarkers in serum or urine. Clinical characteristics of patients were obtained from the electronic medical record. Patients with incomplete, inconclusive, or inadequate data were excluded.
The final patient population was 147 with confirmed CA (mean age = 70 years, 76% were men, and 51% were Black). ATTR CA was present in 61% of the population and AL CA in 39%. Compared to the AL patients, ATTR patients were older; they also exhibited more ventricular enlargement and dysfunction, thicker ventricular walls, and higher extracellular volumes by cardiac MRI. The presence of the typical cardiac MRI pattern and negative light chains carried a sensitivity of 73% and a specificity of 98% for ATTR CA.
Among the 73% with biopsy-proven CA, the cardiac MRI/light chain algorithm carried a sensitivity of 69% and a specificity of 98%. Among the 11% with a positive PYP scan and biopsy, the algorithm carried a sensitivity of 93% and a specificity of 100%. The authors concluded using cardiac MRI and a light chain biomarkers algorithm to diagnose CA subtype was highly specific for ATTR, which could prevent diagnostic delays and lower costs for identifying these patients.
COMMENTARY
After viewing advertisements for tafamidis, more of my patients are concerned they have CA. If there is a legitimate clinical suspicion for CA, I order an echocardiogram; if it is suspicious, I order a cardiac MRI and light chains. If these tests are negative for CA, unless clinical suspicion is high I don’t move on to a PYP scan or biopsy (usually of peripheral fat). What Slivnick et al addressed is how far cardiologists have to go to diagnose the subtype of CA. This is important because AL CA means a referral to hematology/oncology, and ATTR CA means the patient could be a candidate for tafamidis. PYP involves radiation and does not help clinicians diagnose alternate conditions when it is negative. Biopsy is invasive, especially of the heart.
This is why Slivnick et al tested a different approach. In their algorithm, the authors recommended starting with light chains measurements. If they are present, refer the patient to hematology/oncology. If negative, order a cardiac MRI. If the cardiac MRI pattern is typical for ATTR, the work is finished. If the cardiac MRI pattern is atypical, further evaluation with PYP scan or biopsy is indicated. The authors showed this algorithm is highly specific for ATTR CA and modestly specific for AL CA.
The strength of the Slivnick et al study is the high number of ATTR CA patients. About half the patient population was Black; hereditary ATTR commonly afflicts this population in the United States.1 The authors also comprehensively evaluated light chains in serum and urine, including immunofixation or electrophoresis. Beyond these strengths, there are weaknesses to consider. The authors excluded 30% of the potential study population for missing, inadequate, or inconclusive data. Thus, the raw sensitivity and specificity may not be as good as that observed in their more selective population. This underscores the difficulty in diagnosing CA in some patients and why some are going to need PYP and biopsy.
Further, this was a retrospective study, so researchers did not assess the confounders. In addition, their patients presented with more advanced disease; thus, false-positives attributed to other hypertrophic cardiomyopathies were minimized.
In the final analysis, the Slivnick et al study suggests that perhaps we can adopt a less is more approach to the diagnosis of ATTR CA, but this concept needs to be confirmed in a prospective study.
REFERENCE
1. Shah KB, Mankad AK, Castano A, et al. Transthyretin cardiac amyloidosis in Black Americans. Circ Heart Fail 2016;9:e002558.
A retrospective study of patients with confirmed cardiac amyloidosis showed negative light chain biomarkers and a typical pattern of cardiac amyloid on cardiac MRI was highly specific for the diagnosis of the transthyretin subtype and may obviate the need for further testing before starting treatment.
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