Selenium Intervention Registry Randomized Trial in Heart Failure

Heart failure (HF) is a complex, systemic syndrome characterized not only by impaired cardiac function but also by metabolic, inflammatory, and neurohormonal disturbances. Despite advances in guideline-directed medical therapy, patients with HF continue to experience high rates of hospitalization and mortality, highlighting the need for additional therapeutic strategies.

Selenium is an essential trace element incorporated into selenoproteins that play key roles in redox regulation, mitochondrial function, immune modulation, and thyroid hormone metabolism. Observational data from European populations, where dietary selenium intake is relatively low, have demonstrated associations between low selenium status and increased risk of incident HF, impaired functional capacity, reduced quality of life, and higher mortality. Mechanistically, selenium deficiency may contribute to impaired mitochondrial oxidative phosphorylation, increased oxidative stress, and cardiomyocyte dysfunction.

While prior randomized studies of selenium supplementation have yielded mixed results, these have largely been conducted in populations with adequate baseline selenium levels or have not specifically targeted patients with HF. Smaller studies and subgroup analyses suggest potential benefits on cardiac function and clinical outcomes, but definitive evidence is lacking.

The SIRI-HF trial is designed to address this evidence gap using a pragmatic, registry-based randomized clinical trial (RRCT) design. The study is embedded within established national heart failure registries in Sweden (SwedeHF) and Norway (NHFR), enabling large-scale recruitment and efficient long-term follow-up through linkage with national healthcare and administrative registries. This approach allows for comprehensive capture of clinical events, including hospitalizations and mortality, in a real-world setting.

A total of 4,326 adult patients with a diagnosis of heart failure will be randomized in a 1:1 ratio to receive either oral selenium supplementation (200 µg daily) or matching placebo, in addition to standard care. The trial is double-blind, with participants, investigators, and outcome assessors masked to treatment allocation. Recruitment is planned over approximately four years, with follow-up extending up to five years depending on enrollment timing.