Hydroxychloroquine exposure and downstream confirmation of transthyretin cardiac amyloidosis following nuclear imaging: a real-world analysis
C Tabaja, S Myers, W JaberAbstract
Background
Hydroxychloroquine (HCQ) cardiotoxicity can phenotypically and scintigraphically mimic transthyretin cardiac amyloidosis (ATTR), resulting in positive PYP scans in the absence of true amyloid infiltration and raising concern for potential diagnostic misclassification. We sought to evaluate the frequency of downstream ATTR diagnosis and biopsy confirmation among HCQ-exposed patients undergoing nuclear cardiac imaging.
Methods
We performed a retrospective analysis using the TriNetX Research Network. Adult patients with documented HCQ exposure who underwent nuclear cardiac imaging for suspected infiltrative cardiomyopathy were identified. The index event was the first nuclear imaging study. The primary outcome was downstream confirmation of ATTR-CA, defined as transthyretin amyloidosis diagnosis, tafamidis initiation, or endomyocardial biopsy occurring after imaging. Patients were followed longitudinally over 1 year.
Results
Among 376 HCQ-exposed patients undergoing nuclear cardiac imaging, 42 (11.2%) met criteria for downstream ATTR-CA diagnosis or treatment. However, only 12 of these 42 patients (28.6%) underwent endomyocardial biopsy. The majority of patients diagnosed with ATTR-CA were treated with Tafamidis without histological confirmation. Representative multimodality imaging illustrating phenotypic and scintigraphic overlap is shown in Figure 1.
Conclusions
In HCQ-exposed patients, a positive PYP scan may not reliably distinguish ATTR from drug-induced cardiotoxicity. In our cohort, most patients diagnosed or treated for ATTR lacked histologic confirmation. These findings suggest that reliance on scintigraphy alone in this population may lead to diagnostic misclassification and exposure to costly, potentially unnecessary disease-specific therapy. Tissue confirmation should be strongly considered before treatment initiation.Figure