QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis

Abstract Backgrounds: Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with preserved ejection fraction heart failure (HFpEF). Methods and Results: We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface electrocardiogram during hospitalization. QRS morphology was available and classified into three categories among 960 HFpEF subjects as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the three fQRS categories, anterior/lateral fQRS showed significantly higher BNP/troponin levels (both p<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all p<0.05). Anterior/lateral fQRS HFpEF patients exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all p<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted HR: 1.90, p<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all p<0.05) by using Cox regression models.Conclusions: The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such HFpEF patients likely benefits from targeted therapeutic interventions.