Inciardi, RM; Vaduganathan, M; Claggett, B; AbouEzzeddine, OF; Borlaug, BA; Desai, AS; Jhund, PS; ... Solomon, SD; + view all Inciardi, RM; Vaduganathan, M; Claggett, B; AbouEzzeddine, OF; Borlaug, BA; Desai, AS; Jhund, PS; Lam, CSP; Minamisawa, M; Lewis, EF; Redfield, MM; Shah, SJ; Fontana, M; Pfeffer, MA; McMurray, JJV; Solomon, SD; - view fewer (2025) Application of a transthyretin amyloid cardiomyopathy score to heart failure with mildly reduced or preserved ejection fraction. European Journal of Heart Failure 10.1002/ejhf.3698. (In press).

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Abstract

Aims: The safety and efficacy of heart failure (HF)-directed medical therapy among patients who might be considered for further diagnostic evaluation to rule out transthyretin amyloid cardiomyopathy (ATTR-CM) is largely unknown. // Methods and results: We applied a previously validated ATTR-CM screening score in patients with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and assessed treatment effect of sodium–glucose cotransporter 2 inhibitors (SGLT2i), angiotensin receptor–neprilysin inhibitor (ARNI) and mineralocorticoid receptor antagonists (MRAs) based on their score-based ATTR-CM risk, from the DELIVER, PARAGON-HF and TOPCAT Americas trials. We applied a re-derived five-variable modified ATTR-CM score (range −1 to 9) which included age, male sex, hypertension, left ventricular ejection fraction <60%, posterior wall thickness ≥12 mm. We calculated the modified ATTR-CM risk score from DELIVER (available in 4085 patients; 65%), PARAGON-HF (4067; 85%) and TOPCAT Americas (645; 37%). Median scores were 5 (interquartile range [IQR] 4–6) in DELIVER and 4 (IQR 3–6) in both PARAGON-HF and TOPCAT Americas. Higher modified ATTR-CM score was associated with greater risk of the primary endpoint for each trial. However, ATTR-CM risk score did not significantly modify the treatment effect of dapagliflozin (pinteraction = 0.85), sacubitril/valsartan (pinteraction = 0.10), or spironolactone (pinteraction = 0.57). The safety profile of each drug was consistent irrespective of modified ATTR-CM score. // Conclusions: Among three large contemporary HFmrEF/HFpEF trials, the safety and efficacy of SGLT2i, ARNI, and MRA were not modified in patients at risk for ATTR-CM, suggesting that the diagnostic process to rule out amyloidosis should not necessarily delay the introduction of conventional HF medical therapies. // Clinical Trial Registration: ClinicalTrials.gov Identifiers: DELIVER, NCT03619213; PARAGON-HF, NCT01920711; TOPCAT, NCT00094302.

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