Avoiding Unnecessary Cardiac Biopsy by Developing an Algorithm for Amyloidosis

There is consensus that a wild-type transthyretin amyloidosis (ATTRwt) diagnosis can be made without a biopsy as long as there are negative monoclonal protein studies and a positive technetium-99m pyrophosphate (Tc- 99m PYP) scan. Monoclonal proteins can be found in as many as 25% to 30% of patients with ATTR. More invasive biopsies, including endomyocardial biopsy, may be required because fat aspirate is only positive in approximately 15% of patients with ATTR. Furthermore, free light chain (FLC) ratios can increase in renal insufficiency cases, and it has been suggested that a ratio of 0.37:3.1 would account for the modified catabolism in renal failure cases. In addition, light chain amyloidosis (AL) with a difference between involved and uninvolved FLC (dFLC) under 5 mg/dL is not uncommon, occurring in 15% of AL patients. Therefore, it is critical that diagnostic algorithms be both sensitive and precise, because ATTRwt and AL are different diseases that require different clinical approaches for management. A cohort of amyloidosis patients was used to develop a decision-making algorithm that helps avoid unnecessary heart biopsies.

Included in the analysis were patients with AL and ATTRwt who had been examined between January 2012 and July 2018, within 90 days of their diagnosis. If patients did not have FLCs or serum immunofixation (IFE) within 90 days of diagnosis, they were excluded from the analysis. dFLC was defined as the absolute value of κ−λ for all patients.

The study included 998 patients divided into 3 cohorts for analysis. In the first, presumed ATTR was defined as a normal serum IFE and FLC ratio. The second cohort was “indeterminate,” defined as not meeting criteria for group 1 or 3. In the third cohort, presumed AL was defined as an abnormal FLC ratio and a dFLC >5 mg/dL.

In the first group (presumed ATTR group), which comprised 20% of the overall population, there were a total of 24 patients with AL. The researchers noted that the AL patients in this group were younger, more likely to be female, and more likely to have proteinuria, thinner interventricular septa, and positive urine IFE.

In the third cohort, however, the presumed AL group made up 60% of the total population. Finally, the indeterminate cohort 2 represented 20% of the population. AL patients in this cohort were more predominantly female, had thinner interventricular septa, positive urine IFE, and lower N-terminal-pro hormone B-type natriuretic peptide.

Of the 21 “presumed AL” patients who were diagnosed with ATTR, 5 had positive Tc- 99m PYP scans. In all of the “miscategorized” patients, biopsy clarified diagnoses.

The development of an effective algorithm to interpret and manage abnormal monoclonal protein studies in the context of presumed ATTR can be based on these variables.

Source: Dispenzieri A, Ezzeddine OA, Muchtar E, et al. Working towards an algorithm to avoid unnecessary cardiac biopsy. Presented at: XVII International Symposium on Amyloidosis 2020; September 14-18, 2020. Abstract PW137.

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