Clinical outcomes and treatment response according to ATTR-CM risk in HFpEF: a real-world cohort study
C E Tsai, Z W Chen, Y H Hung, M C Chen, P J Liao, C H Tsai, L Y Lin, C K Wu, Y H LinAbstract
Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized among patients with heart failure with preserved ejection fraction (HFpEF). The ATTR-CM score has been proposed as a screening tool to identify patients at high risk of ATTR-CM. However, it remains uncertain whether a high ATTR-CM risk profile modifies the effectiveness or safety of conventional HF medical therapies, such as renin–angiotensin system inhibitors (RASI), beta-blockers (β-blockers), and mineralocorticoid receptor antagonists (MRAs).
Aims
To investigate the prognostic value of the ATTR-CM score and its interaction with conventional HF medical therapies in a large real-world HFpEF cohort.
Methods
Using the National Taiwan University Hospital–Integrated Medical Database, we identified patients with HFpEF based on diagnostic codes, echocardiographic parameters, and clinical criteria. The ATTR-CM score was calculated and patients were stratified into high-risk (score ≥6) and low-to-intermediate risk (score <6) groups. Major outcomes included (1) a composite outcome of cardiovascular death (CVD) and heart failure hospitalization (HHF), and (2) all-cause mortality. Cox proportional hazards models were used to assess associations between ATTR-CM risk and outcomes after multivariable adjustment for relevant clinical covariates. Interaction analyses were performed to evaluate whether treatment effects of RASI, β-blockers, and MRAs differed according to ATTR-CM score. Restricted cubic spline analyses were performed to evaluate treatment effects across the continuous ATTR-CM score.
Results
Among 7848 patients with HFpEF (mean follow-up 4.0 ± 3.4 years), 1984 (25.3%) were classified as high risk for ATTR-CM. High-risk patients had significantly increased risks of the composite outcome of CVD and HHF (adjusted hazard ratio [aHR] 1.14, 95% confidence interval [CI] 1.05–1.24) and all-cause mortality (aHR 1.25, 95% CI 1.15–1.35) compared with low-to-intermediate risk patients. Interaction analyses revealed no significant interaction between ATTR-CM risk groups and the treatment effects of conventional HF therapies on the composite outcome (p for interaction = 0.857, 0.360, 0.436, respectively). For all-cause mortality, a significant interaction was observed for β-blocker use (p for interaction = 0.022), with greater mortality reduction among patients with lower ATTR-CM scores. Nevertheless, β-blocker therapy remained safe in high-risk patients without evidence of harm.
Conclusion
In this real-world HFpEF cohort, a high ATTR-CM score identified patients at increased risk of adverse outcomes but did not attenuate the overall benefit or safety of conventional HF medical therapies. These findings may imply the safety of conventional HF medical therapies (such as RASI, β-blockers, and MRAs) in patients with cardiac amyloidosis.