Impact of the implementation of standardised early identification and diagnosis of transthyretin amyloidosis in high-risk patients: protocol of a high-quality diagnostic study (HI-QUAL ATTR)
S N Zhang, H Shi, Y M Xu, Y Li, L A, H C Shi, Y Zhang, J B GeAbstract
Background
Transthyretin (ATTR) amyloidosis is a fatal disease associated with substantial clinical burden, which occurs in either wild-type (ATTRwt) or hereditary (ATTRv) form. Despite diagnostic and treatment advances, the disease, especially ATTRwt amyloidosis, remains under-recognised and underdiagnosed due to its nonspecific, multisystem symptoms and low clinical awareness, highlighting the urgent need to improve standardised diagnostic practices.
Purpose
The HI-QUAL ATTR study aims to improve the quality of ATTR amyloidosis diagnosis in China by implementing standardised, guideline-based procedures for the early identification and diagnosis among high-risk patients.
Methods
This multicentre, prospective, single-arm, interventional study will enrol about 4,000 adult patients at high risk of ATTR amyloidosis from around 50 sites in China. Selected study sites must be tertiary public hospitals with a cardiovascular (CV) department and the necessary facilities for ATTR amyloidosis diagnosis, have previously diagnosed ≥1 case of cardiac ATTR amyloidosis, and treated ≥100 patients with left ventricular hypertrophy (LVH) per year. Eligible patients are aged ≥60 years and have documented symptomatic heart failure with left ventricular ejection fraction ≥40% and LVH. Exclusion criteria include known aetiologies of myocardial diseases, anomalies of serum free light chain or serum/urine immunofixation electrophoresis, acute myocardial infarction within 6 months before screening, and inability to undergo 99mTc-pyrophosphate (PYP). Patients will undergo a standardised diagnostic process (Fig. 1). The study intervention involves knowledge training, operation training and post-training verification among investigators (Table 1). CV department investigators will receive training on disease knowledge, standard diagnostic pathways, and genetics. Investigators in echocardiology (ECHO) and nuclear medicine departments will receive training on disease knowledge, standardised operating procedures (SOPs), imaging parameter reporting, and hands-on operation training in SOPs and image interpretation. Post-training verification will assess site-level compliance. Extra training will be arranged if quality audit is off target. The primary endpoint is the proportion of patients diagnosed with ATTR amyloidosis in high-risk populations. Secondary endpoints include the proportion of patients with ATTRwt amyloidosis in diagnosed patients, concordance between local investigators and central reviewers in ECHO and 99mTc-PYP readings, risk factors for 99mTc-PYP-diagnosed ATTR amyloidosis, and genotype distribution in patients with ATTRv amyloidosis. All analyses will be descriptive with no preplanned hypotheses.
Conclusion
This study is the first to assess the impact of standardised early identification and diagnosis of ATTR amyloidosis in high-risk populations in China. The study findings are expected to greatly improve early detection and diagnosis of ATTR amyloidosis.Figure 1.Study designFor image description, please refer to the figure legend and surrounding text.Table 1.Study interventionsFor image description, please refer to the figure legend and surrounding text.