Heart Failure and Mildly Reduced Ejection Fraction

Heart failure is a serious condition in which the heart is unable to pump blood effectively, and it remains a leading cause of hospitalization and death worldwide despite advances in treatment. Selenium is an essential micronutrient that plays an important role in cellular energy production, antioxidant defense, and overall cardiovascular function. Low selenium levels are common among patients with heart failure in Northern Europe, and observational studies have shown that selenium deficiency is associated with an increased risk of hospitalization and death. In cases of severe deficiency, such as in Keshan disease, heart dysfunction can be reversed with selenium supplementation, suggesting a potential causal relationship. However, it is not yet known whether selenium supplementation can improve clinical outcomes in patients with heart failure when added to standard medical therapy. The SIRI-HF trial is a randomized, placebo-controlled study designed to evaluate whether daily supplementation with 200 micrograms of selenium, in addition to guideline-directed medical therapy, improves outcomes in patients with heart failure. The primary endpoint is a composite of recurrent heart failure hospitalizations and cardiovascular death. Secondary endpoints include all-cause mortality, changes in symptoms and functional status, and safety outcomes. This study will include patients from Sweden and Norway and aims to determine whether correcting selenium deficiency can improve prognosis in heart failure.

The INITIATE-HF study is a cluster randomized controlled trial that aims to find out if reminding doctors about treatment guidelines for iron deficiency in adults with heart failure who are hospitalized and have evidence of iron deficiency changes the subsequent use of intravenous (IV) iron. Two groups of hospitalized adult patients with known heart failure and iron deficiency will be compared: * Group 1 will include doctors who receive a notification with their patient's iron storage test results and guideline recommendations related to the use of IV iron. * Group 2 will include doctors who do not receive this notification and continue with usual standard of care. The study will measure if this provider-facing notification affects physician use of recommended IV iron treatment in eligible patients with heart failure, left ventricular ejection fraction less than 50%, and iron deficiency. Secondarily, if there is an increased use of IV iron observed in the intervention group, this study will evaluate whether there are differential health outcomes (i.e., fewer subsequent hospital visits and lower risk of death) of patients whose providers were assigned to the intervention group.

Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) constitutes of four medications that substantially reduce morbidity and mortality, and improve quality of life. In routine clinical practice, various physician- and patient-related factors lead to suboptimal initiation and uptitration of GDMT to optimal dosing, which is associated with worse patient outcomes. A perceived major barrier to the optimalization of GDMT are changes in kidney function and electrolytes, which prompts physicians to halt uptitration, reduce doses, or even discontinue GDMT. Changes in kidney function and electrolytes during optimalization of GDMT are common, but not associated with adverse events. The hypothesis of this study is that a reduction in the number of kidney function assessments during initiation and uptitration of GDMT in HFrEF patients will lead to higher achieved doses of GDMT without safety concerns.