Key result
High ATTR-CM risk in HFpEF is linked to ~14% higher cardiovascular death or HF hospitalization.
Why the study?
Although the ATTR-CM score screens for transthyretin amyloid cardiomyopathy among HFpEF patients, it remained uncertain whether a high ATTR-CM risk profile modifies the effectiveness or safety of conventional heart failure medical therapies such as RASI, beta-blockers, and MRAs.
Does a high ATTR-CM risk score increase the risk of cardiovascular death, heart failure hospitalization, and all-cause mortality or modify the effectiveness of conventional heart failure medical therapies in patients with HFpEF?
Cohort (n=7,848)
Does a high ATTR-CM risk score increase the risk of cardiovascular death, heart failure hospitalization, and all-cause mortality or modify the effectiveness of conventional heart failure medical therapies in patients with HFpEF?
In a large real-world HFpEF cohort, a high ATTR-CM risk score independently predicted worse cardiovascular outcomes and mortality, while conventional heart failure therapies (RASI, beta-blockers, and MRAs) remained safe and effective without evidence of harm in high-risk patients.
High ATTR-CM risk score identifies higher-risk HFpEF patients; extends prognostic utility but leaves open randomized confirmation of therapy interactions.
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.
No takes yet. Share an insight, caveat, or question.
Tsai et al. (2026) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) (n=7,848). High ATTR-CM risk (score ≥6) and conventional HF medical therapies (RASI, β-blockers, MRAs) vs. Low-to-intermediate ATTR-CM risk (score <6) was evaluated on Composite outcome of cardiovascular death (CVD) and heart failure hospitalization (HHF) (aHR 1.14, 95% CI 1.05–1.24). High ATTR-CM risk (score ≥6) in HFpEF increased cardiovascular death or HF hospitalization (aHR 1.14, 95% CI 1.05-1.24) without attenuating conventional HF therapy benefits.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: