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

Abstract

Background 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 heart failure with preserved ejection fraction (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 ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/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). Patients with anterior/lateral fQRS HFpEF 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 hazard ratio 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 patients with HFpEF likely benefits from targeted therapeutic interventions.

Keywords: QRS duration; fragmented QRS complex; heart failure with preserved ejection fraction; mortality.

Figure 1. Relationship between the percentage of cardiac ischemic area and different coronary arteries.

A, The percentage of total myocardial perfusion defects in non‐fQRS, inferior and anterior/lateral fQRS among 210 out of 326 (64.4%) study participants with known CAD. B through D, The percentage of myocardial perfusion defects in the RCA, LCX, and LAD in non‐fQRS, inferior and anterior/lateral fQRS. CAD indicates coronary artery disease; fQRS, fragmented QRS; LAD, left anterior descending artery; LCX, left circumflex artery; and RCA, right coronary artery. *p<0.05 vs non‐fQRS; ^# p<0.05 vs inferior fQRS.

Figure 2. Myocardial perfusion defects in (A) non‐fQRS, (B) inferior fQRS, and (C) anterior/lateral fQRS with SPECT imaging.

D through F, Correlation between total myocardial perfusion defect and TDI‐derived myocardial early relaxation (TDI‐e′) velocity, systolic (TDI‐s′) velocities, and LV filling pressure E/e′. fQRS indicates fragmented QRS; LV, left ventricular; SPECT, myocardial perfusion single‐photon emission computed tomography; and TDI, tissue Doppler imaging.

Figure 3. Association between the presence of coronary slow flow and cardiac function.

A, The percentage of coronary slow flow during coronary angiography among 203 out of 634 (32.0%) non‐CAD study participants. B through D, Comparisons of the TDI‐s′, TDI‐e′, and average E/e′ in normal versus slow coronary flow non‐CAD study participants. CAD indicates coronary artery disease; fQRS, fragmented QRS; and TDI, tissue Doppler imaging.

Figure 4. Crude and adjusted hazard ratio with corresponding 95% CIs for 3 fQRS strata (non‐fQRS as the reference) on hospitalization for heart failure, cardiovascular mortality, all‐cause mortality, and composite end point.

The multivariate model was adjusted for age, sex, body mass index, hypertension, diabetes, heart failure, hyperlipidemia, cardiovascular disease, estimated glomerular filtration rate, and left ventricular ejection fraction. fQRS indicates fragmented QRS.

Figure 5. Kaplan–Meier survival curves of clinical outcomes according to fQRS strata (left).

Condensed illustrations and graphical abstract about the clinical features, functional correlates, and outcomes of 3 fQRS strata in HFpEF (right). BNP indicates B‐type natriuretic peptide; CAD, coronary artery disease; CV, cardiovascular; fQRS, fragmented QRS; HF, heart failure; HHF, hospitalization for heart failure; HFpEF, heart failure with preserved ejection fraction; LAD, left anterior descending artery; and LCX, left circumflex artery.