Cardiopulmonary Exercise Testing Correlates with Quantitative Left Ventricular [99mTc]-DPD Uptake in Transthyretin Amyloid Cardiomyopathy

<b>Background/Objectives</b>: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and ^99mTc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools for diagnostic and disease monitoring. We aimed to investigate the complementary role and correlation between both methods, focusing on their combined potential as a strong prognostic framework for monitoring disease progression and evaluating treatment efficacy. <b>Methods</b>: A total of 44 patients with diagnosed ATTR-CM, who underwent ^99mTc-DPD scintigraphy and SPECT/CT imaging as well as CPET, were included. All patients were divided into two groups based on the median DPD retention index (low DPD uptake: ≤5.0, n = 22; high DPD uptake: >5.0, n = 22). <b>Results</b>: The mean age was 78 years, with 82% of participants being male. Significant correlations were observed between peak VO₂ and DPD retention index (r = -0.355, <i>p</i> = 0.018) as well as between peak VO₂ at anaerobic threshold with DPD retention index (r = -0.391, <i>p</i> = 0.009). Interestingly, there was no strong correlation between VE/VCO₂ slope and the retention index. A strong association was identified between cardiac biomarkers and peak VO₂, specifically for NT-proBNP (r = -0.530, <i>p</i> < 0.001) and Troponin T (r = -0.431, <i>p</i> < 0.001). <b>Conclusions</b>: In ATTR-CM, significant correlations were observed between key CPET parameters and quantitative cardiac DPD uptake, which further reflects on disease severity and functional impairment. Our findings highlight the utility of integrating CPET and SPECT/CT for comprehensive patient assessment in ATTR-CM.