Canadian Cardiovascular Society/Canadian Heart Failure Society 2025 Guideline Update for Pharmacologic Management of Heart Failure With Nonreduced Ejection Fraction (LVEF > 40%).

Heart failure with nonreduced ejection fraction (HFnrEF), defined as signs and symptoms of heart failure (HF) with a left ventricular ejection fraction (LVEF) of > 40%, continues to increase in prevalence with significant effects to patients, their care givers, and the health care system broadly. Historically, this population has been divided into HF with mildly reduced (HFmrEF) or HF with preserved ejection fraction (HFpEF). However, contemporary evidence indicates that patients across the spectrum of LVEF > 40% experience similar clinical outcomes and, importantly, respond consistently to several key pharmacotherapies. Adoption of the term HFnrEF provides a practical and unified framework for clinical decision-making, reducing ambiguity and promoting consistent application of evidence-based therapies. To support clinicians in translating evidence into practice, the Canadian Cardiovascular Society (CCS) and the Canadian Heart Failure Society (CHFS) present this guideline, which is focused on pharmacological management of symptomatic heart failure with nonreduced ejection fraction (HFnrEF). Underpinned by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology and meta-analyses, outcomes of interest include pharmacotherapies shown to reduce the risk of HF hospitalization (HFH) and improve patient well-being in this population. The guideline offers concise recommendations for 4 key classes of pharmacological therapies: sodium-glucose cotransporter-2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and evidence-based drugs with glucagon-like peptide-1 (GLP-1) receptor agonist activity. Recommendations are complemented by practical tips to guide the initiation, titration, and maintenance of these foundational treatments. By emphasizing therapeutic consistency across the > 40% LVEF spectrum, this guideline aims to streamline care pathways and enhance the delivery of guideline-directed medical therapy for patients with symptomatic HFnrEF in real-world settings.