Study finds gaps in recommended cardiac amyloidosis testing

Many patients evaluated for two common forms of cardiac amyloidosis never received the testing recommended to confirm or rule out the diseases, a large analysis of U.S. electronic health records found. This gap can delay treatment for conditions in which timely care is crucial, according to the study authors.

The retrospective study, published in eJHaem, drew on de-identified electronic health record (EHR) and integrated claims-clinical data covering January 2017 through June 2023. Investigators led by Muhamed Baljevic, M.D., of Vanderbilt University Medical Center, examined the diagnostic workups recorded in the 24 months before a first diagnosis of light chain (AL) amyloidosis, wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), or both.

The two conditions can have similar manifestations but differ in prognosis and treatment, the authors noted, which makes an accurate, early diagnosis important. Untreated AL amyloidosis carries a median survival of a year or less, while untreated individuals with ATTRwt-CM survive a median of about five years, according to figures cited in the study.

“AL amyloidosis and ATTR-CM are challenging to diagnose as initial symptoms are often nonspecific, which could lead to misdiagnosis, mistreatment, or delayed appropriate treatment,” the authors wrote. “Prompt and accurate diagnosis is critical, especially for patients with AL amyloidosis, due to poor survival.”

Across the three cohorts — 1,653 patients with AL amyloidosis, 1,055 with ATTRwt-CM, and 59 with both — roughly half to two-thirds underwent any relevant test: 53%, 61% and 66%, respectively. Fewer received a workup specific to AL amyloidosis, at 42%, 40% and 49%.

The gap was most pronounced for the testing that guidelines recommend. Complete monoclonal protein testing, which includes a serum free light chain assay paired with serum and urine immunofixation electrophoresis and is roughly 99% sensitive for detecting AL amyloid, was documented for 17% of the AL cohort, 15% of the ATTRwt-CM cohort, and 17% of those with both diagnoses.

On the ATTRwt-CM side, half of that cohort and 46% of the dual-diagnosis group received any ATTRwt-CM–specific test. Among patients who had a 99m-technetium pyrophosphate (PYP) scan, a noninvasive route to an ATTR-CM diagnosis, only 9% in the ATTRwt-CM cohort and 5% in the combined group also had complete monoclonal protein testing within the recommended window of before or up to seven days after the scan.

Where testing did occur, it was often handled outside specialty cardiology. Cardiac specialists were associated with at least 34% of workups and general medicine providers with at least 29%, the investigators found.

“As notable proportions of the workups were completed outside cardiac specialties, raising disease and diagnostic awareness for [cardiac amyloidosis], AL amyloidosis, and ATTR-CM in general or non-cardiology healthcare settings could improve compliance with guideline-recommended diagnostic pathways,” the authors wrote. “This could potentially contribute to early and improved diagnosis, more prompt treatment initiation, and better patient outcomes.”

The researchers flagged limitations common to claims and HER-based research, including coding errors, incomplete data, and the possibility that some diagnosis codes reflected rule-out evaluations rather than confirmed disease. Tests performed more than 24 months before diagnosis, or outside the captured health systems, would also have been missed.

Still, the authors concluded that notable shares of patients did not receive testing that guidelines recommend and that better disease and diagnostic education for clinicians across specialties and subspecialties is needed to support earlier, more accurate diagnosis and timely treatment.