Impact of SGLT2 inhibitors on functional class in patients with transthyretin cardiac amyloidosis: a retrospective matched study
R Spoladore, M Milani, A Granata, F Cavallier, D Restelli, A FarinaAbstract
Background
Transthyretin cardiac amyloidosis (ATTR-CM) is characterized by progressive heart failure (HF) and worsening functional capacity. Furthermore, advanced classes of HF may limit the indication for disease-specific treatments in ATTR-CM or may limit the prognostic benefits of these therapies. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve outcomes in HF, but their effect on functional status in ATTR-CM is not well established.
Purpose
To evaluate the impact of SGLT2 inhibitor therapy on New York Heart Association (NYHA) functional class in patients (pts) with ATTR-CM and, secondly, whether these drugs are able to implement the indication for disease-specific therapy (Tafamidis).
Methods
We retrospectively analyzed 60 ambulatory pts with confirmed ATTR-CM, followed between January 2022 and June 2025. Thirty pts treated with an SGLT2 inhibitor (empagliflozin or dapagliflozin 10 mg daily) were matched 1:1 with controls not receiving SGLT2i. Baseline clinical and echocardiographic characteristics were comparable between groups. The primary endpoint was change in NYHA functional class at 12 months and the proportion of pts able to Tafamidis therapy compared to baseline. NYHA class was analyzed as an ordinal variable using non-parametric tests.
Results
At baseline, most pts were in NYHA class III [SGLT2i group 22 pts (73%), controls 21 pts (70% 70%)]. After 12 months, 19 patients (63%) receiving SGLT2i improved by at least one NYHA class, compared with 4 controls (13%) (p < 0.001). Median NYHA class improved from III to II in the treated group (p < 0.001), while remaining unchanged in controls (p = 0.48). No relevant adverse events or treatment discontinuations were reported. At baseline, all pts in NYHA class III were not considered eligible for Tafamidis therapy; of these, 40% of pts receiving SGLTi were deemed eligible for Tafamidis therapy after 12 months.
Conclusions
In this retrospective matched study, SGLT2 inhibitor therapy was associated with a significant improvement in NYHA functional class in pts with ATTR-CM, allowing a significant portion of patients, not considered candidates for tafamidis therapy at baseline, to become suitable for this specific therapy.