Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study.

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Cardiac sympathetic neuronal dysfunction is an early marker in wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM). [123I]-MIBG imaging evaluates cardiac sympathetic innervation but lacks volumetric activity quantification in current methods. This study aims to quantify cardiac sympathetic neuronal dysfunction in ATTRwt-CM using [123I]-MIBG SPECT/CT and correlate findings with functional and structural cardiac parameters from echocardiogram and cardiac magnetic resonance imaging (CMR). We conducted a single-center, descriptive, cross-sectional study to quantify absolute myocardial sympathetic function in ATTRwt-CM using [123I]-MIBG SPECT/CT. Retrospective reconstruction allowed for absolute tracer-uptake quantification of the left ventricle, overall and segmented, in kBq/mL, SUV and percentage of the injected dose (%ID). Echocardiography, CMR, and bone scintigraphy were performed according to clinical standards. Segmented [123I]-MIBG SPECT/CT values were correlated with global longitudinal strain (GLSS) on echocardiography, native-T1, and extracellular volume (ECV) on CMR using SPECT/CT fused with CMR. Twenty-nine ATTRwt-CM patients (75.8±6.6 years, 90% male) were prospectively included. All exhibited cardiac sympathetic neuronal dysfunction, with a median late heart-to-mediastinum ratio of 1.69[1.45-1.89] and a washout rate of 22.7% (16.4-27.3%). SUVmean, SUVpeak, SUVmax and %ID were 1.80 ± 0.78, 3.84 ± 1.41, 4.46 ± 1.68 and 0.46 ± 0.18 respectively, correlating with semi-quantitative [123I]-MIBG measures. No correlations were found with GLSS on echocardiography or native T1 and ECV on CMR. The current study demonstrates the feasibility of volumetric quantification of [123I]-MIBG SPECT/CT in ATTRwt-CM. SUVmean, SUVpeak, SUVmax and %ID correlate with semi-quantitative measures but not with key cardiac parameters on echocardiography or CMR. This confirms the sensitivity of [123I]-MIBG SPECT/CT to different aspects of cardiac function or pathology. EudraCT ref. 2020-003350-72, retrospectively registered 20 March 2023. https://classic. gov/ct2/show/NCT05776212.