99mTC-DPD bone scintigraphy in ATTR-CM: are we missing patients? can you suggest me more titles?

Introduction

99mTc-DPD scintigraphy is the standard non-invasive imaging modality for diagnosing transthyretin cardiac amyloidosis (ATTR-CM). However, its performance across the full phenotypic spectrum is not fully validated. Reduced sensitivity has been reported, particularly in early-stage hereditary disease. In such cases, reliance on scintigraphy alone may delay diagnosis, making endomyocardial biopsy (EMB) essential in selected patients.

Aim

To assess the diagnostic performance of 99mTc-DPD scintigraphy in hereditary (hATTR-CM) and wild-type (wtATTR-CM) disease and identify predictors of non-diagnostic scans.

Methods

We performed a single-center retrospective study of patients diagnosed with ATTR-CM between 2022 and 2024. Scans were classified as negative with a Perugini score of 0–1. All patients with negative scans underwent EMB. TTR genotyping was performed in all cases to distinguish hATTR-CM from wtATTR-CM.

Results

One hundred patients were included (51% hATTR-CM; 49% wtATTR-CM); 90% had positive scintigraphy. Patients with negative scans were younger (60 ± 5 vs 77 ± 1 years; p=0.009) and all had hereditary disease (10 [100%] vs 0). Sensitivity was 100% in wtATTR-CM and 77% in hATTR-CM, including 77% in Val30Met and 100% in non-Val30Met variants.

Patients with negative scans had lower symptom burden (NYHA III/IV: 0 vs 28%; p=0.06) and required less diuretic therapy (20% vs 53%; p=0.046). Echocardiography showed lower interventricular septal thickness (12.7 ± 0.5 vs 16.3 ± 0.5 mm; p=0.001) and a trend toward lower sPAP. Biomarkers were also lower: NT-proBNP (280 vs 1136 pg/mL; p=0.001) and troponin (14 vs 38 ng/L; p=0.02). EMB confirmed amyloid deposition in all patients with negative scans.

On multivariable analysis, septal thickness ≤13 mm independently predicted a negative scan (OR 6.77; 95% CI 1.25–36.53; p=0.026).

Conclusion

99mTc-DPD scintigraphy shows high diagnostic accuracy in ATTR-CM but reduced sensitivity in younger patients and hereditary disease, particularly Val30Met variants with limited remodeling. In this subgroup—especially with septal thickness ≤13 mm—EMB is crucial to avoid missed diagnoses and ensure timely therapy. These findings support a tailored diagnostic strategy integrating clinical assessment, genotyping, and myocardial histology.For image description, please refer to the figure legend and surrounding text.