Yield and Predictors of Conversion on Serial Amyloid Nuclear SPECT/CT in At-Risk Populations for Transthyretin Cardiac Amyloidosis

Abstract Background and Objective Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure, yet data guiding surveillance strategies in high-risk individuals remain limited. This study evaluated the incidence, imaging patterns, and clinical predictors of SPECT/CT conversion among patients undergoing serial Tc-99m PYP/HMDP imaging. Methods We conducted a retrospective cohort study of 106 patients who underwent repeat Tc-99m PYP or HMDP cardiac SPECT/CT between 2018 and 2025. Patients with a positive initial scan or repeat imaging within less than 12 months were excluded. Conversion was defined as new Perugini grade ≥1 with any myocardial radiotracer uptake on follow-up. Clinical characteristics, biomarkers, genetic testing, and extracardiac biopsy findings were analyzed. Univariable and multivariable Cox regression identified predictors of conversion. Results Over a mean follow-up of 3.2 years, 14 patients (13.2%) showed imaging conversion. Echocardiographic parameters and absolute biomarker levels were comparable between groups; however, a ≥30% rise in NT-proBNP was more frequent among converters (71.4% vs. 38.1%, p=0.018). On univariable analysis, hypertension was associated with a lower hazard of conversion (HR 0.27; p=0.023), while co-occurrence of carpal tunnel syndrome and spinal stenosis was associated with a significantly higher hazard (HR 3.90; p=0.024). In multivariable analysis adjusted for age and sex, this musculoskeletal phenotype remained independently associated with conversion (adjusted HR 5.95; p=0.019). Conclusions The combined presence of carpal tunnel syndrome and spinal stenosis identifies a high-risk phenotype for future imaging conversion. These exploratory findings support serial amyloid SPECT/CT for surveillance and highlight the value of musculoskeletal comorbidities in refining risk stratification for ATTR-CA.