Abstract Body (Do not enter title and authors here): Introduction
Despite new advances in heart failure (HF) management, underutilization of guideline-directed medical therapy (GDMT) persists. In addition, contemporary data on GDMT utilization and whether sex differences exist is unclear. We aim to characterize GDMT use across HF subtypes, investigate sex-based disparities in utilization, and explore these impacts on patient quality of life markers and clinical outcomes.

Methods
Patients with HF were enrolled in the heart function clinic (HFC) in Edmonton, Alberta, from Feb 2018 to Nov 2022. Medication records (renin-angiotensin system inhibitors [RAASi], angiotensin receptor neprilysin inhibitors [ARNI], β-blockers, mineralocorticoid inhibitors [MRA], sodium-glucose cotransporter 2 inhibitors [SGLT2i], and glucagon-like peptide 1 receptor agonist [GLP-1 RA]) over 3 years and clinical comorbidities using ICD-10 codes were obtained. We administered the Kansas City Cardiomyopathy Questionnaire Score (KCCQ-12) at enrolment and 6—or 12-month follow-ups, with changes ≥5 defined as clinically significant. We assessed the association between GDMT and sex to changes in KCCQ-12 scores and clinical outcomes.

Results
Our HFC cohort of 1431 HF patients (median age 68, 29% female) included 52% with reduced (HFrEF), 20% with mildly reduced (HFmrEF), and 28% with preserved (HFpEF) ejection fraction. Median baseline KCCQ-12 score was 75 (IQR 33) and was similar between HF subtypes. ARNI, SGLT2i, and MRA use in HFpEF remains lower compared to HFrEF/HFmrEF (p<0.001), with gaps in treatment persisting over 3 years. Across HF subtypes, GDMT utilization rates were similar between sexes except for SGLT2i in HFmrEF (19.1% male vs. 7.5% female, p=0.02). Controlling for clinical covariates, RAASi (aHR 0.54, 95% CI 0.41-0.70), ARNI (aHR 0.58, 95% CI 0.43-0.80), GLP-1 RA (aHR 0.43, 95% CI 0.19-0.97), and females (aHR 0.72, 95% CI 0.58-0.91) were associated with lower all-cause mortality. ARNI use was also associated with improved follow-up KCCQ12 scores (aOR 1.57, 95% CI 1.00-2.45).

Conclusion
Despite evidence of improved KCCQ-12 scores and reduced all-cause mortality, GDMT remains underutilized, particularly in HFpEF patients. While we found no sex-based disparities in GDMT utilization, females showed better clinical outcomes in our HF cohort. To improve patient outcomes, further research is needed to address barriers to implementing new GDMT across the heart failure spectrum.