Light-Chain Abnormalities Associated with Final ATTR-CM Diagnosis in Patients with Positive PYP/Abnormal PCD

Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a significant cause of heart failure, particularly among older adults with heart failure with preserved ejection fraction. It can be noninvasively diagnosed using Tc-99m pyrophosphate (PYP) imaging, but only when normal markers of plasma cell dyscrasia (PCD) have helped exclude light-chain amyloidosis as the cause of cardiomyopathy. Recognizing that PCD testing abnormalities are common in patients with ATTR-CM, Cozzolino and colleagues sought to define the distribution of PCD testing abnormalities, and the extent to which light-chain abnormalities are associated with a final diagnosis of ATTR-CM among patients who have received a positive PYP scan.

The investigators conducted a retrospective, cohort study of 378 patients from October 2014 to January 2019. These patients had suspected ATTR-CM and had been referred for PYP imaging. PCD markers consisted of serum-free light-chain assays and serum/urine immunofixation electrophoresis. The investigators reported finding abnormal results in approximately one-third (36%) of the cases. Laboratory, echocardiogram, tissue biopsy, and electrocardiogram data were also collected from these patients. Final diagnosis of amyloidosis was determined by either a tissue biopsy or multidisciplinary clinical evaluation at the Amyloidosis Center at Boston Medical Center.

After patients were screened for exclusion factors, including incomplete data, the final study population was 82 cases. Positive PYP scans were present in 62 cases, all of whom on final adjudication were diagnosed with ATTR-CM. No patients in either group had light-chain amyloidosis, and the majority of the negative PYP scan group had no final diagnosis of cardiac amyloidosis. The baseline characteristics of the full study population were predominantly male patients with an average age of 75 years. When comparing the PYP-positive and PYP-negative groups, most clinical factors were relatively similar; there were minor differences in average age, body mass index, troponin levels, inferolateral wall thickness, and total voltage.

The adjudication of ATTR-CM was accomplished ultimately by endomyocardial biopsy in 39% (N = 25), extracardiac biopsy in 25% (N = 16), and multidisciplinary clinical evaluation in 36% (N = 23).

The range of PCD abnormalities among patients with positive PYP scans and ATTR-CM was evaluated. Overall, although 26% of patients had ≥1 abnormal PCD markers, the majority (68%) of patients with adjudicated ATTR-CM had free light chain ratio elevation between 1.65 and 3.1, with negative serum/urine immunofixation electrophoresis suggesting that endomyocardial biopsy may be avoidable in these cases of patients with similar PCD test results.

Source: Cozzolino M, Alreshq R, Lilleness B, et al. Abnormal light chain testing and diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) among patients referred for technetium-99M pyrophosphate imaging. Presented at: ACC.21, American College of Cardiology 70th Annual Scientific Session & Expo, May 15-17, 2021.

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