Non‐invasively quantified changes in left ventricular activation predict outcomes in patients undergoing cardiac resynchronization therapy

Abstract

Background Changes in left ventricular (LV) activation after cardiac resynchronization therapy (CRT) influence survival but are difficult to quantify noninvasively. Methods and Results We studied 527 CRT patients to assess whether noninvasive quantification of changes in LV activation, defined by change (Δ) in QRS area (QRSA), can predict outcomes after CRT. The study outcome was time until LV assist device(LVAD), cardiac transplant, or death. The three‐dimensional QRSA was measured from clinical 12 lead ECGs which were transformed into vectorcardiograms using the Kors method. QRSA was calculated as (QRSx2 + QRSy2 + QRSz2)1/2; ΔQRSA was calculated as post‐QRSA minus pre‐QRSA, where a negative value represents a reduction in LV activation delay. Kaplan–Meier plots and multivariable Cox proportional hazards models were used to relate ΔQRSA area with outcomes after stratifying the population into quartiles of ΔQRSA. The median baseline QRSA of 93.6 µVs decreased to 59.7 µVs after CRT. Progressive reductions in QRSA with CRT were associated with a lower rate of LVAD, transplant, or death across patient quartiles (P < .001). In Cox regression analyses, ΔQRSA was associated with outcomes independent of QRS morphology and other clinical variables (Q1[greatest decrease] vs Q4[smallest change=reference], HR 0.45, CI, 0.30‐0.70, P < .001). There was no interaction between ΔQRSA and QRS morphology. Conclusions CRT induced ΔQRSA was associated with clinically meaningful changes in event‐free survival. ΔQRSA may be a novel target to guide lead implantation and device optimization.

Reduction in the QRS area after cardiac resynchronization therapy is associated with survival and echocardiographic response

“…The finding of electrical substrate modification being an independent factor aids the previous findings that LV‐paced conduction times by CRT are unrelated to baseline QRS morphology and that a poor correlation exists between intrinsic activation delay (qLV) and LV‐paced conduction time 9 . Also, another study reported that ΔQRS area was associated with event‐free survival independently from QRS morphology 10 . As for ΔQRS area's value in relation to endpoints, the findings of the present analysis are in agreement with a study that showed a correlation of acute hemodynamic CRT‐benefit with QRS area decrease 11 .…”

Sex differences in left ventricular electrical dyssynchrony and outcomes with cardiac resynchronization therapy

“… 12 Increased QRSA has also been associated with improved likelihood of survival free of heart transplant or LV assist device (LVAD) after CRT, 8 , 13 independent of QRS morphology and duration. Our group 9 and others 11 demonstrated that an in-treatment decrease in QRSA (ie, CRT-induced reduction in LV electrical dyssynchrony) is associated with significantly improved outcomes. QRSd reflects the time between start of ventricular activation and the conclusion of ventricular depolarization, regardless of which ventricle contains the most activation delay.…”

“…The QRS area (QRSA) is a robust, validated, noninvasive, vectorcardiographically derived measure of left ventricular (LV) electrical dyssynchrony that has demonstrated substantial relevance to CRT candidacy. [8][9][10][11][12][13] Increased QRSA is a stronger predictor of LV activation delay than QRSd or morphology 10 and is a robust predictor of LV reverse remodeling with CRT. 12 Increased QRSA has also been associated with improved likelihood of survival free of heart transplant or LV assist device (LVAD) after CRT, 8,13 independent of QRS morphology and duration.…”

Concomitant changes in ventricular depolarization and repolarization and long‐term outcomes of biventricular pacing

“…3 Novel ECG dyssynchrony markers including R-wave amplitude in V1-V2, vectorcardiographic QRS area, or time from QRS onset to the intrinsicoid deflection in V1, V5, aVL, and aVF have been shown to predict response to BiV pacing better than prolonged QRS duration. [4][5][6][7][8] However, their clinical implementation is limited largely due to the lack of availability during routine clinical practice making postimplantation prognostication using standard 12-lead ECG challenging.…”

“…Current clinical guidelines on BiV pacing recommend using prolonged QRS duration as a marker of dyssynchrony on the standard 12‐lead electrocardiogram (ECG), 2 but the change in QRS duration with BiV pacing is inconsistently associated with likelihood of response 3 . Novel ECG dyssynchrony markers including R‐wave amplitude in V1‐V2, vectorcardiographic QRS area, or time from QRS onset to the intrinsicoid deflection in V1, V5, aVL, and aVF have been shown to predict response to BiV pacing better than prolonged QRS duration 4–8 . However, their clinical implementation is limited largely due to the lack of availability during routine clinical practice making postimplantation prognostication using standard 12‐lead ECG challenging.…”