Elsevier

Heart Rhythm

Volume 8, Issue 5, May 2011, Pages 692-699
Heart Rhythm

Clinical
Heart failure
Electrophysiologic substrate and intraventricular left ventricular dyssynchrony in nonischemic heart failure patients undergoing cardiac resynchronization therapy

https://doi.org/10.1016/j.hrthm.2011.01.017Get rights and content

Background

Electrocardiographic imaging (ECGI) is a method for noninvasive epicardial electrophysiologic mapping. ECGI previously has been used to characterize the electrophysiologic substrate and electrical synchrony in a very heterogeneous group of patients with varying degrees of coronary disease and ischemic cardiomyopathy.

Objective

The purpose of this study was to characterize the left ventricular electrophysiologic substrate and electrical dyssynchrony using ECGI in a homogeneous group of nonischemic cardiomyopathy patients who were previously implanted with a cardiac resynchronization therapy (CRT) device.

Methods

ECGI was performed during different rhythms in 25 patients by programming their devices to biventricular pacing, single-chamber (left ventricular or right ventricular) pacing, and native rhythm. The electrical dyssynchrony index (ED) was computed as the standard deviation of activation times at 500 sites on the LV epicardium.

Results

In all patients, native rhythm activation was characterized by lines of conduction block in a region with steep activation–recovery interval (ARI) gradients between the epicardial aspect of the septum and LV lateral wall. A native QRS duration (QRSd) >130 ms was associated with high ED (≥30 ms), whereas QRSd <130 ms was associated with minimal (25 ms) to large (40 ms) ED. CRT responders had very high dyssynchrony (ED = 35.5 ± 3.9 ms) in native rhythm, which was significantly lowered (ED = 23.2 ± 4.4 ms) during CRT. All four nonresponders in the study did not show significant difference in ED between native and CRT rhythms.

Conclusion

The electrophysiologic substrate in nonischemic cardiomyopathy is consistent among all patients, with steep ARI gradients co-localizing with conduction block lines between the epicardial aspect of the septum and the LV lateral wall. QRSd wider than 130 ms is indicative of substantial LV electrical dyssynchrony; however, among patients with QRSd <130 ms, LV dyssynchrony may vary widely.

Introduction

Cardiac resynchronization therapy (CRT) using biventricular pacing is a relatively new treatment modality designed to restore synchrony with the objective of improving cardiac mechanical performance in congestive heart failure.1, 2, 3, 4 CRT has been demonstrated to be clinically effective in 60% to 70% of patients, and its indication as therapy has increased exponentially over the last several years. A number of different echocardiographic measures have been used clinically to select potential CRT candidates. The recently concluded PROSPECT2 trial has shown that none of the echocardiographic measures provides a consistent basis for clinical decisions regarding CRT implants. The ECG QRS duration (QRSd) is deemed to be the most clinically relevant measure for CRT. Although CRT has been shown to benefit the majority of symptomatic patients with wide QRSd >130 ms, reports on the usefulness of CRT in moderate ranges of QRSd (100–130 ms) are conflicting. The RethinQ trial3 showed that CRT is not beneficial for patients with narrow QRSd. However, another recent study4 demonstrated potential short-term improvement with CRT in patients with QRSd <120 ms. This indicates that there may be heart failure patients with QRSd in the range from 100 to 130 ms who may respond well to CRT, but the measures of dyssynchrony used in RethinQ could not identify this group. With the reliability of echocardiographic measures in question (PROSPECT), the quest for an alternative measure of dyssynchrony in the context of CRT continues.

Electrocardiographic imaging (ECGI)5, 6, 7, 8 is a novel imaging modality for cardiac electrophysiology, based on 250 body surface ECGs and an accurate, patient specific heart–torso anatomy derived from an ECG-gated computed tomographic scan. It noninvasively generates electroanatomic maps of epicardial potentials (voltage maps), electrograms, and activation and repolarization sequences. A previous study using ECGI in eight heart failure patients with ischemic cardiomyopathy undergoing CRT showed that the electrophysiologic substrate is extremely heterogeneous among these patients and that the efficacy of CRT depends strongly on the patient-specific substrate and pacing electrode placement relative to this substrate.8 This was a study in a very heterogeneous group of patients with varying degrees of coronary disease and ischemic cardiomyopathy. The objective of the current study is to characterize the left ventricular (LV) electrophysiologic substrate and electrical dyssynchrony in a population of nonischemic cardiomyopathy patients previously implanted with a CRT device. A quantitative index for LV electrical dyssynchrony is defined and computed, and its relationship with QRSd is studied.

Section snippets

Methods

ECGI was performed in each patient in each of the following rhythms: (1) biventricular CRT pacing (CRT); (2) LV pacing (LV-P); (3) right ventricular (RV) pacing (RV-P); and (4) nonpaced native rhythm (NAT), if applicable. Two patients had optimized interventricular (V-V) delays different from the nominal value, and ECGI was performed with both optimal (CRT-OPT) and nominal (CRT-NOM) V-V delays. The nominal V-V delay is the standard “factory” setting (simultaneous biventricular pacing).

Custom

Study population

Between January 2007 and April 2010, 25 heart failure patients (age 51 ± 18 years, range 6–68 years) with a CRT implant and nonischemic dilated cardiomyopathy were recruited retrospectively for the study. Patients were selected from the database of patients who were implanted with a CRT/CRT-ICD device and were being seen at the heart failure clinic at Barnes Jewish Hospital and/or St. Louis Children's Hospital. The following inclusion criteria were used for patient selection: patients without

LV electrophysiologic substrate

The native activation pattern in nonischemic cardiomyopathy is similar among patients, in contrast to the large variability observed in ischemic CRT patients by Jia et al.8 The activation pattern is characterized by lines of conduction block extending from base to apex and located between the epicardial aspect of the septum and the LV lateral wall. This results in U-shaped activation around the line of block and very delayed activation (later than 80th percentile of QRSd) of a large portion of

Acknowledgments

We thank Timothy Sekarski for superb technical expertise in acquiring the echocardiographic images and Timothy Street for capable assistance in performing computed tomographic scans for this study.

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The first two authors contributed equally to this work. This study was supported by Grants R01-HL-33343-26 and R01-HL-49054-18 from the National Heart, Lung, and Blood Institute to Dr. Rudy. This publication was also made possible by Grant UL1 RR024992 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Dr. Rudy is the Fred Saigh Distinguished Professor at Washington University in St. Louis. Dr. Rudy co-chairs the scientific advisory board and holds equity in CardioInsight Technologies (CIT). CIT does not support any research conducted by Dr. Rudy, including that presented here.

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