Prevalence and reclassification of monoclonal gammopathy in elderly HFpEF patients undergoing ATTR-CM screening: A PATCH-HFpEF sub-study
C E Tsai, Y H Hung, C H Wei, M C Chen, P C Liao, C H Tsai, M F C, L Y Lin, A L Yu, C C Chao, C K Wu, Y H LinAbstract
Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an important cause of heart failure with preserved ejection fraction (HFpEF) in elderly patients. Exclusion of light chain amyloidosis (AL-CM) is mandatory during evaluation; however, monoclonal gammopathy of undetermined significance (MGUS) is common in this population and may complicate interpretation of monoclonal protein testing. In addition, renal dysfunction, which is highly prevalent among the elderly, can alter free light chain ratio (FLCR) values and further confound diagnostic assessment. eGFR-adjusted FLCR cutoffs have been shown to provide diagnostic sensitivity comparable to traditional thresholds for the detection of AL-CM.
Aim
To determine the prevalence of MGUS in elderly HFpEF patients undergoing ATTR-CM screening and to evaluate the impact of eGFR-adjusted FLCR thresholds on MGUS classification and the ATTR diagnostic pathway.
Methods
This analysis was derived from a prospective multicenter screening trial, Prevalence of Transthyretin Amyloid Cardiomyopathy in Taiwanese Elderly Patients with Heart Failure with Preserved Ejection Fraction (PATCH-HFpEF), which enrolled patients aged ≥60 years with HFpEF who underwent standardized evaluation for ATTR-CM according to established criteria. Patients with monoclonal protein and FLCR assessment were included in the present study. MGUS was defined as the presence of monoclonal proteins in serum or urine, and/or abnormal FLCR, following consultation with hematology specialists. Traditional FLCR cutoffs (0.26-1.65) were compared with eGFR-adjusted ranges: 0.46-2.62 (eGFR 45-59 mL/min/1.73 m²), 0.48-3.38 (eGFR 30-44 mL/min/1.73 m²), 0.54-3.30 (eGFR <30 mL/min/1.73 m²).
Results
A total of 184 patients were enrolled. MGUS prevalence was 21.7% using traditional FLCR thresholds, and no MGUS-positive patients were diagnosed with AL-CM or multiple myeloma. Stratified by 99mTc-PYP scan visual score (VS), prevalence was 18.2% in VS 0 (n=132), 29.3% in VS 1 (n=41), 33.3% in VS 2 (n=6), and 40.0% in VS 3 (n=5). Among confirmed ATTR-CM patients, the prevalence was 37.5%. Patients with lower eGFR were more likely to meet MGUS criteria under traditional FLCR cutoffs. Application of eGFR-adjusted FLCR cutoffs led to reclassification of a subset of patients, reducing overall MGUS prevalence to 13.0%. The corresponding prevalence were 9.8% in VS 0, 17.1% in VS 1, 33.3% in VS 2, 40.0% in VS 3, and 37.5% in confirmed ATTR-CM.
Conclusion
MGUS is highly prevalent among elderly patients with HFpEF and often confounds the diagnostic screening for ATTR-CM. The implementation of eGFR-adjusted FLCR thresholds reduces MGUS overclassification, simplifies clinical decision-making, and potentially lowers medical expenditure.