Changes in QRS Area and QRS Duration After Cardiac Resynchronization Therapy Predict Cardiac Mortality, Heart Failure Hospitalizations, and Ventricular Arrhythmias

Abstract

Background Predicting clinical outcomes after cardiac resynchronization therapy (CRT) and its optimization remain a challenge. We sought to determine whether pre- and postimplantation QRS area (QRS_area) predict clinical outcomes after CRT. Methods and Results In this retrospective study, QRS_area, derived from pre- and postimplantation vectorcardiography, were assessed in relation to the primary end point of cardiac mortality after CRT with or without defibrillation. Other end points included total mortality, total mortality or heart failure (HF) hospitalization, total mortality or major adverse cardiac events, and the arrhythmic end point of sudden cardiac death or ventricular arrhythmias with or without a shock. In patients (n=380, age 72.0±12.4 years, 68.7% male) undergoing CRT over 7.7 years (median follow-up: 3.8 years [interquartile range 2.3-5.3]), preimplantation QRS_area ≥102 μVs predicted cardiac mortality (HR: 0.36; P<0.001), independent of QRS duration (QRSd) and morphology (P<0.001). A QRS_area reduction ≥45 μVs after CRT predicted cardiac mortality (HR: 0.19), total mortality (HR: 0.50), total mortality or heart failure hospitalization (HR: 0.44), total mortality or major adverse cardiac events (HR: 0.43) (all P<0.001) and the arrhythmic end point (HR: 0.26; P<0.001). A concomitant reduction in QRS_area and QRSd was associated with the lowest risk of cardiac mortality and the arrhythmic end point (both HR: 0.12, P<0.001). Conclusions Pre-implantation QRS_area, derived from vectorcardiography, was superior to QRSd and QRS morphology in predicting cardiac mortality after CRT. A postimplant reduction in both QRS_area and QRSd was associated with the best outcomes, including the arrhythmic end point.

Keywords: QRS area; QRS duration; cardiac resynchronization therapy; left bundle branch block; vectorcardiography.

Figure 1

Vectorcardiography in cardiac resynchronization therapy. The vectorcardiogram displays the various features of the ECG, such as the QRS complex, in the form of “loops,” which are determined from vectors representing successive, instantaneous mean electrical forces throughout the cardiac cycle. A, A representation of the 3 vectorcardiogram leads (X, Y, and Z), according to Frank's orthogonal lead system. B, Two‐dimensional vector loops in the frontal (X‐Y leads), sagittal (Y‐Z leads), and transverse (X‐Z leads) planes from a patient with a left bundle branch block. The QRS _area is calculated as the integral sum of the area bound by the QRS complex and the isoelectric baseline in each vectorcardiogram lead (X, Y, and Z).

Figure 2

Receiver‐operator characteristic curves. Graphs show areas under the receiver‐operator characteristic curves (AUC) for QRSd, QRS area, and QRS morphology (LBBB) in the whole cohort. AUC indicates area under the curve; CRT, cardiac resynchronization therapy; LBBB, left bundle branch block.

Figure 3

Clinical outcomes according to pre‐implantation QRS area. Kaplan–Meier survival curves for the various end points according to precardiac resynchronization therapy QRS _area. Results of univariate Cox proportional hazard models are expressed in terms of hazard ratio (HR) (95% CI). HF indicates heart failure; MACE, major adverse cardiac events.

Figure 4

Postimplantation changes in QRS area and QRS duration. Box‐and‐whisker plots of QRS area (left) and QRS duration (QRSd) (right) before and after CRT implantation. The horizontal line denotes the median, whereas the lower and upper limits of the box denote the first and third quartiles. The limits of the vertical bar denote maximum and minimum. CRT indicates cardiac resynchronization therapy.

Figure 5

QRS area and QRS duration in relation to cardiac mortality. Kaplan–Meier survival curves and univariate HR and (95% CI for QRS area (QRS _area) and QRS duration (QRSd) in relation to cardiac mortality. *Refers to the interaction between changes in QRSarea and QRSd after CRT. HR indicates hazard ratios.

Figure 6

Secondary clinical end points according to changes in QRS area and QRS duration. Kaplan–Meier survival curves for the various end points according to postcardiac resynchronization therapy reductions in QRS _area (≥45 μVs) QRS duration (QRSd; to any value below baseline). HF indicates heart failure; MACE, major adverse cardiac events.

Figure 7

Postimplantation changes QRS area and QRS duration according to left ventricular lead position. The figure shows post– cardiac resynchronization therapy changes in QRS area (ΔQRS _area) and QRS duration (ΔQRSd) according to circumferential (upper panel) and longitudinal (lower panel) left ventricular lead positions. In the box‐and‐whisker plots, the horizontal line denotes the median, whereas the lower and upper limits of the box denote the first and third quartiles. The limits of the vertical bar denote maximum and minimum. NS indicates not significant.

Figure 8

Sudden cardiac death and ventricular arrhythmias according to postimplantation changes in QRS area and QRS duration. Kaplan–Meier survival curves for the combined end point of sudden cardiac death (SCD), ventricular tachycardia (VT)/ventricular fibrillation (VF), or shock according to postimplantation reductions in QRS area (QRS _area, ≥45 μVs) QRS duration (QRSd to any value below baseline). *Refers to the comparison of the group with concomitant reductions in QRS _area (≥45 μVs) and QRSd against the group with no reductions in either variable. HR indicates hazard ratio.