Scar burden assessed by Selvester QRS score predicts prognosis, not CRT clinical benefit in preventing heart failure event and death: A MADIT-CRT sub-study☆,☆☆
Introduction
Cardiac resynchronization therapy (CRT) improves prognosis and ameliorates symptoms in selected heart failure (HF) patients. However, up to one third of patients may not benefit from CRT but are still subjected to adverse effects and costs [1]. Several factors that may predict favorable CRT response determined by echocardiography parameters and/or event-free survival have been identified, including QRS duration ≥ 150 ms [2], non-ischemic heart failure etiology [3], female sex [2], left ventricular (LV) lead placement (non-apical [4], at site of latest activation [5] and away from scar [6]) and left bundle branch block (LBBB) QRS morphology. In addition, newer strict LBBB criteria indicative of complete left bundle branch block [7] have been shown to predict CRT success better than traditional LBBB criteria [8]. Finally, low myocardial scar burden either measured by cardiac magnetic resonance imaging with late gadolinium enhancement (CMR-LGE) or estimated by ECG Selvester QRS score has been linked to favorable CRT outcome [9], [10]. Importantly, previous studies on the value of both ECG estimation of scar using the Selvester QRS score and scar burden by CMR-LGE in predicting CRT response have not featured any non-CRT-D arm and thus could not evaluate the effect of scar burden on CRT clinical benefit.
We aimed to test whether QRS score was a significant predictor of echocardiographic and clinical benefit after CRT implantation in the MADIT-CRT population.
We specifically hypothesized that among CRT recipients, high myocardial scar burden estimated by ECG Selvester QRS score would be predictive of: a) less increase of left ventricular ejection fraction (LVEF), b) less reduction of left ventricular end-systolic volume (LVESV), and c) a smaller improvement in event-free survival compared to implantable cardioverter-defibrillator (ICD).
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Study patients
MADIT-CRT enrolled subjects of either sex who were more than 21 years of age with ischemic cardiomyopathy (New York Heart Association [NYHA] class I or II) or non-ischemic cardiomyopathy (NYHA class II only), sinus rhythm, an LVEF of 30% or less and QRS duration of 130 ms or more as described previously [2], [11]. Further exclusion criteria included existing indication for CRT at time of enrollment, previously implanted pacemaker, implantable cardioverter defibrillator (ICD) or CRT, previous
Study patients
A total of 1733 patients were included in this substudy, 1029 in the CRT-D arm and 704 in the ICD arm. The CRT-D arm and the overall population had similar baseline characteristics and similar use of cardiac drugs at time of enrollment as shown in Table 1. Mean follow-up was 2.4 years. There were 441 that reached the clinical endpoint of HF event or death. The average QRS score was 5.2 in the overall study population (4.2 in the LBBB subgroup). The distribution of conduction types in the
Discussion
The major finding of the present study was that in the LBBB subgroup, scar burden estimated by ECG using the Selvester QRS score did not predict CRT clinical benefit, but rather prognosis regardless of CRT implantation.
Because CRT has been shown to be most effective in LBBB, coupled with the notion that extensive scar could prevent CRT effect, one may hypothesize that scar burden would be most important for predicting prognosis in the CRT-D LBBB subgroup. However, we found that CRT was equally
Conclusion
In the LBBB subgroup, myocardial scar estimated by electrocardiographic Selvester QRS scoring predicts prognosis in heart failure patients and may identify echocardiographic responders to CRT. However, QRS score cannot be used to determine who will benefit clinically from CRT-D over implantation of ICD only. Future research should determine if these findings are also present with other markers of myocardial scar, such as cardiac magnetic resonance imaging.
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Cited by (0)
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Financial disclosures: No extramural funding was used to support this work.
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Author contributions: WZ and JPD acquired data as part of the MADIT-CRT study. DGS, ZL and GSW conceived of this substudy. ZL and SM designed the statistical analysis plan, which was critically reviewed by DGS, WZ and JPD. BW later added complementary analyses to the statistical analysis plan. ZL applied Selvester QRS scoring to all ECGs. DGS scored ECGs that ZL flagged as difficult to analyze. SM conducted all statistical analyses. All co-authors participated in interpretation of results. BW and ZL produced the initial draft of the manuscript, which was then revised and approved by all remaining co-authors.
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Co-lead authors.