Research Article: Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling

Date Published: June 6, 2019

Publisher: Public Library of Science

Author(s): Adrian M. Suszko, Sachin Nayyar, Andreu Porta-Sanchez, Moloy Das, Arnold Pinter, Eugene Crystal, George Tomlinson, Rupin Dalvi, Vijay S. Chauhan, Elena G. Tolkacheva.


Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response.

Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT.

Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1–2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.

Partial Text

Cardiac resynchronization therapy (CRT) restores electromechanical left ventricular (LV) synchrony and has been shown to reverse structural remodeling and improve clinical outcomes in heart failure patients with New York Heart Association (NYHA) class II-III function, LV ejection fraction (LVEF) <35%, and QRS duration (QRSd) >120ms [1]. Yet, a large proportion of these patients (~30–40%) do not respond to CRT, often due to the presence of minimal electromechanical dyssynchrony or suboptimal LV lead pacing/placement [2]. In view of this, targeted LV lead implantation to sites of latest electrical or mechanical activation has improved CRT response rate [3]. However, the assessment of mechanical activation time and dyssynchrony based on echocardiographic-derived measures of regional strain and wall motion can be limited by large observer variability, which may account for the lack of consistent improvement in CRT response when using these metrics for patient selection. In contrast, the evaluation of electrical dyssynchrony using QRSd and bundle branch block (BBB) morphology appears more reliable and the CRT response rate increases in patients with more prolonged QRSd and left BBB (LBBB) [4]. Nonetheless, LV activation timing can still be quite heterogeneous for any given QRSd or BBB morphology due to varying spatial/transmural scar mass, scar border zones of slow conduction and lines of functional conduction block [5]. Structural remodeling in this manner can change the direction of activating wavefronts in addition to delaying LV activation time, which can manifest on the surface 12-lead ECG as QRS fragmentation [6].

The main findings of our study are as follows: (i) QRSp independently predicts functional CRT response in cardiomyopathy patients, unlike QRSd, LBBB or fQRS, (ii) QRSp ≥7 identifies CRT responders with greater accuracy than QRSd ≥150ms or fQRS, and (iii) QRSp decreases in CRT responders while increasing in CRT non-responders, whereas QRSd and fQRS do not change irrespective of CRT response.