A Prospective, Multicenter, Intervention Study to Evaluate the Impact of the Implementation of Standardized Transthyretin Amyloidosis (ATTR) Early Identification and Diagnosis in ATTR High Risk Population
This multicenter, prospective, single-arm, interventional study will enroll about 4,000 adult patients at high risk of ATTR amyloidosis from around 50 sites in China. Eligible patients are aged ≥60 years and have documented symptomatic heart failure with left ventricular ejection fraction ≥40% and LVH. Exclusion criteria include known etiologies of myocardial diseases, anomalies of serum free light chain or serum immunofixation electrophoresis, acute myocardial infarction within 6 months before screening, and inability to undergo 99mTc-PYP. Patients will undergo a 14-week diagnostic process. The study intervention involves knowledge training, operation training and post-training verification among investigators. Knowledge training for CV department investigators will cover disease-specific knowledge, standard diagnostic pathways, and genetics; training for investigators in echocardiology (ECHO) and nuclear medicine departments will focus on disease knowledge, standardized operating procedures (SOPs), and imaging parameter reporting. Operation training includes hands-on training in SOPs and image interpretation for ECHO and nuclear medicine investigators. 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, concordance between local investigators and central reviewers in ECHO and 99mTc-PYP readings, and genotype distribution. All analyses will be descriptive with no pre-planned hypotheses. Risk factors associated with 99mTc-PYP-diagnosed ATTR amyloidosis will be analyzed via logistic regression models.
• Age ≥ 60 years, at the time of signing the informed consent (ICF).
• Documented diagnosis of symptomatic heart failure (NYHA class I-III) at enrolment, and current diagnosis or a medical history of HF
• Documented Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) \> 300 pg/mL at enrolment.
• Documented LVEF ≥40% at enrolment.
• Documented LVH defined as end-diastolic wall thickness of ≥12 mm (IVS or PWT) on transthoracic Echocardiogram (TTE) at enrolment.
• Patients who are willing and able to comply with all scheduled visits, laboratory tests, and other study procedures.
• Willing and able to undergo 99mTc-PYP scintigraphy.
• Capable of giving signed ICF as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.