Prognostic Impact of Long-Term Sodium Zirconium Cyclosilicate-Integrated Medical Therapy in Patients with Systolic Heart Failure

<b>Background:</b> Sodium zirconium cyclosilicate (SZC) is a novel potassium-binding agent with strong evidence supporting its efficacy in normalizing hyperkalemia. However, the long-term prognostic impact of SZC-integrated medical therapy in patients with systolic heart failure and baseline hyperkalemia remains uncertain. <b>Methods:</b> This study included patients with heart failure and a left ventricular ejection fraction (LVEF) of <50% who were prescribed SZC for hyperkalemia between July 2020 and February 2025. Patients who continued SZC therapy for two years or until February 2025 were classified into the SZC continuation group and followed from the initiation of SZC. Those who discontinued SZC during the study period were assigned to the SZC discontinuation group, with follow-up commencing from the point of cessation. The two-year cumulative incidence of all-cause mortality or hospital readmission was compared between the groups. <b>Results:</b> A total of 61 patients (median age: 79 years; 33 men; median LVEF: 42%) were included in the analysis. Serum potassium levels significantly decreased in the SZC continuation group (<i>p</i> < 0.001) but remained unchanged in the SZC discontinuation group (<i>p</i> = 0.23). The SZC continuation group demonstrated a trend toward a lower cumulative incidence of the primary outcome compared to the SZC discontinuation group (29% vs. 47%, <i>p</i> = 0.079). Additionally, in the SZC continuation group, the daily doses of renin-angiotensin system inhibitors and mineralocorticoid receptor antagonists increased significantly (<i>p</i> < 0.05 for both). Furthermore, LVEF improved significantly with SZC-integrated medical therapy (<i>p</i> = 0.011), whereas no such changes were observed in the SZC discontinuation group (<i>p</i> > 0.05 for all). <b>Conclusions:</b> Long-term SZC-integrated medical therapy was associated with the sustained normalization of hyperkalemia, optimization of heart failure pharmacotherapy, and improved clinical outcomes in patients with systolic heart failure and baseline hyperkalemia. These findings underscore the need for prospective randomized controlled trials in carefully selected patient populations to validate the benefits of SZC and establish its optimal supportive role in the management of systolic heart failure.