Abstract 4365181: The Association of Cardiac Structure and Function with Incident Stroke in Patients with Heart Failure with Preserved Ejection Fraction: Insights from the TOPCAT and PARAGON-HF Trials

Backgrounds: Stroke is a major complication in patients with heart failure with preserved ejection fraction (HFpEF), associated with significant morbidity and mortality. However, predictors of incident stroke in this population remain insufficiently characterized. Echocardiographic assessment of cardiac structure and function may serve as a valuable tool for stroke risk stratification in patients with HFpEF. Research Question: Which echocardiographic parameters are associated with the risk of stroke in patients with HFpEF? Methods: We pooled data from the echocardiographic sub-studies of the TOPCAT and PARAGON-HF trials, which included patients with HF and a LVEF ≥45%. The primary outcome was the centrally adjudicated incident of all types of strokes. Baseline clinical characteristics and echocardiographic parameters were compared between patients with and without incident stroke. The association of individual echocardiographic parameters with incident stroke was assessed using multivariable Cox models, adjusting for the CHA 2 DS 2 -VASc score, AF, anticoagulant use, systolic blood pressure, body mass index, race, treatment arm, and trial cohort. Results: Among 1,751 patients (654 from TOPCAT and 1,097 from PARAGON-HF; mean age: 73±9 years, female: 51%, mean LVEF: 59±9%, AF: 54%), 71 experienced a stroke over a median follow-up of 3.0 years (rate of 1.4 per 100 patient-years). Patients who had a stroke during follow-up had a higher prevalence of prior stroke, hypertension, and peripheral artery disease at baseline (all p<0.05). After multivariable adjustment, greater LV mean wall thickness (adjusted HR: 1.45, 95% CI: 1.19-1.77 per 1 SD increase) and the presence of mitral annular calcification (MAC, adjusted HR: 1.92, 95% CI: 1.18-3.11) were independently associated with a higher risk of incident stroke ( Figure ). Conversely, other echocardiographic parameters, including LVEF, left atrial volume index, and left atrial strain, were not significant predictors of stroke. These findings were consistent irrespective of AF status, age, sex, prior stroke, anticoagulation use, and trial cohort (all intearaction P>0.05). Conclusion: In this large cohort including over 1,700 patients with HFpEF with extensively well-characterized cardiac structure and function, LV mean wall thickness and MAC were independently associated with a higher risk of stroke, adding mechanistic insight and highlighting their potential role in stroke risk stratification in this population.