To evaluate the effectiveness of positron emission tomography (PET) with [11C]-Pittsburgh Compound-B ([11C]PiB) for detecting transthyretin amyloid (ATTR) cardiomyopathy in patients with transthyretin gene (TTR) variants associated with reduced bone scintigraphy sensitivity, and its ability to detect brain involvement in hereditary transthyretin amyloidosis. This prospective case series included four hereditary ATTR amyloidosis patients with TTR variants associated with reduced bone scintigraphy sensitivity, and two patients with positive bone scintigraphy (one hereditary ATTR and one wild-type ATTR amyloidosis patient). All patients underwent diagnostic work-up at the Groningen Amyloidosis Centre of Expertise between April 2024 and March 2025, including [11C]PiB PET/CT. Cardiac and brain [11C]PiB uptake were assessed visually. Target-to-background ratios (TBRs) and cortical SUV ratios were calculated. TBR ≥1.09 was considered positive for ATTR cardiomyopathy and SUV ratios ≥0.7 was considered positive for brain involvement. Cardiac [11C]PiB uptake was observed in three of four hereditary ATTR amyloidosis patients despite negative bone scintigraphy. In one of four patients, there was visually equivocal radiotracer uptake, but elevated TBRs did indicate ATTR cardiomyopathy. Conversely, both hereditary ATTR and wild-type ATTR amyloidosis patients with a positive bone scintigraphy had negative or inconclusive [11C]PiB PET results. Brain uptake was observed in two asymptomatic patients, while no uptake was seen in two patients with suspected brain involvement. [11C]PiB PET could be an effective tool for detecting ATTR cardiomyopathy in patients with TTR variants associated with reduced bone scintigraphy sensitivity. However, its utility for detecting brain involvement in symptomatic hereditary ATTR patients remains uncertain.

In wild-type transthyretin amyloidosis (ATTRwt), the deposition of transthyretin in the myocardium leads to progressive heart failure. However, little is known about the short-term natural progression of this disease and potential predictors of outcome. Therefore, this study longitudinally analyzed the clinical findings (ECG, echocardiography, and laboratory tests) of 65 patients suffering from ATTRwt at baseline and at follow-up visits after 12 months. In total, 44 patients (67.7%) presented with abnormal ECGs, prolonged PR and QRS durations and low-voltage patterns. Pacemaker placement was performed in eleven patients (16.9%). At the one-year follow-up visit, we detected significant increases in the QRS duration (from 119.7 ± 4.0 to 125.9 ± 4.3 ms; p < 0.05), intraventricular septum thickness (from 18.9 ± 0.5 mm to 19.9 ± 0.5 mm; p < 0.05) and ejection fraction (EF) (from 45.4 ± 2.1% to 38.9 ± 2.6%; p < 0.05) compared with those at the baseline visit. During follow-up, 16 patients (24.6%) died. Predictors of worse outcomes were progression in QRS duration, low EF, reduced renal function, impaired right ventricular function and the need for pacemaker implantation. In ATTRwt, precise evaluation via routine cardiac diagnosis helps to identify patients with an elevated risk of mortality. Patients with prolonged QRS duration, progressive myocardial hypertrophy, right ventricular failure, reduced renal function and the need for cardiac pacemakers are at increased risk for one-year mortality. The online version contains supplementary material available at 10.1186/s13023-025-04078-4.

Relevance of wild-type ATTR amyloidosis (wtATTR) is increasing, due to improved therapeutic and diagnostic options. Despite the significant prevalence of neurological manifestations, there remains low awareness towards the disease, resulting in delayed diagnoses and treatment commencements. Systematic clinical and neurophysiological characterisations of large neurological collectives are lacking, as well as examination of correlations between neurological and cardiological involvement. 75 patients with confirmed initial diagnosis of wtATTR amyloidosis underwent standardised clinical and extended neurophysiological examination (quantitative sensory testing, nerve conduction studies, sympathetic skin response, autonomic testing). Furthermore, cardiac involvement was quantified using laboratory and clinical scores, as well as cardiac tracer uptake in scintigraphy. 84% of the patients suffered from carpal tunnel syndrome (CTS), 62% with bilateral involvement. Neuropathy was present in 71%; one third showed spinal stenosis. CTS operation was performed a median of 10 years before diagnosis. Clinically, the absence of Achilles reflexes and impaired pallesthesia were particularly impressive. No correlation was found between the severity of neurological symptoms and cardiological or scintigraphic parameters. We were able to perform a precise clinical and neurophysiological characterisation in a large cohort of patients. We detected a predominant peripheral neuropathy pattern in a large majority of patients. However, the extent of neurological damage did not correlate with cardiac involvement. The findings may contribute to enhanced awareness among neurologists, potentially leading to earlier diagnosis and initiation of treatment.