Original-clinicalElectrocardiographic imaging of cardiac resynchronization therapy in heart failure: Observation of variable electrophysiologic responses
Introduction
Delayed ventricular activation,1 predominantly of the left ventricle (LV), accompanies more than 30% of advanced heart failure cases. Cardiac resynchronization therapy (CRT) using biventricular pacing has been developed to restore synchrony. CRT improves patients’ symptoms and echocardiographic measures, and it confers a mortality benefit.2 However, many issues related to CRT remain unresolved. For reasons that are not clear, approximately 33% of patients do not respond to CRT [Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial].3 QRS duration (QRSd) as a criterion for patient selection and assessment of response is weak.4, 5 LV lead location may be a factor. The incremental benefit of single-site LV pacing alone is unresolved. The electrical consequences of LV pathology have not been examined.
Although improved mechanical performance is the aim of therapy, CRT is an electrical approach that uses pacing and electrophysiologic principles to modify mechanical behavior. The efficacy of the therapy is initially governed by electrical properties and thus may be limited by electrical dysfunction. Hence, failure to achieve resynchronization could be due, in part, to abnormal local electrical properties, such as slow conduction or conduction block, which are likely to be present in patients with LV disease. Therefore, an understanding of the electrophysiologic effects of CRT is essential, requiring high-resolution electrical mapping of ventricular excitation. Until recently, such information could not be obtained noninvasively.
Electrocardiographic imaging (ECGI) is a novel noninvasive imaging modality developed in our laboratory for determining cardiac excitation through noninvasive electrophysiologic epicardial imaging during a single beat. The method has been validated extensively in a human-shaped torso tank containing normal and abnormal canine hearts6, 7, 8 and in canine experiments,9, 10 demonstrating high accuracy in imaging focal activity, infarct substrate, repolarization gradients, and reentry during ventricular tachycardia. ECGI has been applied in humans11 and compared to direct epicardial mapping during open heart surgery12 and to catheter mapping during ventricular tachycardia.13 In humans, ECGI provided images of cardiac activation and repolarization during normal sinus rhythm, conduction disturbances, atrial flutter, and multisite ventricular pacing. A reconstruction accuracy better than 10 mm was consistently obtained in human subjects.14 Similar to previous studies, we used the ECGI-reconstructed epicardial data in this study to estimate the locations of pacing leads and compared them to the corresponding locations determined from computed tomographic (CT) images. Average accuracy within 10.2 ± 5.1 mm was achieved in locating the pacing sites. With this level of accuracy and extensive validation, ECGI provides a unique tool for noninvasive evaluation of electrophysiologic phenomena, including mechanisms and responses to therapeutic interventions.
In this study, ECGI was applied to eight patients with an implanted CRT device, and ventricular activation during native rhythm and various pacing modes was imaged. Our ultimate goal is to understand the electrophysiologic mechanism(s) that affects responses to CRT and to identify possible use of ECGI in guiding patient selection and lead placement.
This initial study provides preliminary but unique observations on the electrical activity of the heart during CRT and identifies electrical properties that may influence its success as a therapeutic approach. We posed the following hypothesis-driven questions: (1) Is native activation pattern in heart failure patients with left bundle branch block (LBBB) similar in all subjects? (2) Does LV pacing alone evoke similar electrical synchrony as biventricular pacing? (3) Does electrical synchrony correlate with clinical response? (4) Is right ventricular (RV) pacing alone beneficial? These questions were tested in a group of patients with severe LV disease exposed to various pacing modes. The results demonstrated several variables that likely significantly affect pacing efficacy.
Section snippets
Methods
The study evaluated eight heart failure patients (six men and two women; age 72 ± 11 years; New York Heart Association functional class III–IV) with ventricular conduction delay who received CRT through implanted atrial-biventricular pacing device. Six patients had native rhythm with LBBB pattern, one had atrial fibrillation, and one had no underlying rhythm (no AV conduction and no ventricular escape beats) at the time of the study (Table 1). The last two patients were upgraded to
Native rhythm
Native rhythm was imaged in six patients by inactivating the CRT device. Four representative maps are shown in Figure 1. ECG was similar to the preimplant ECG, indicating similar activation sequences. In all six patients, RV epicardial activation started from RV breakthrough 29 ± 7 ms after onset of body surface QRS. This is delayed relative to that in normal young adults.16 Epicardial activation spread radially from the RV breakthrough site, with latest activation of the RV at basal RV or
Discussion
The unique capability of ECGI for noninvasive epicardial mapping was used to determine activation sequences during pacing in a group of eight patients undergoing CRT with the following observations. (1) Activation sequences during native rhythm were heterogeneous among individuals. (2) RV pacing was not effective in resynchronization in most patients. (3) LV pacing often generated similar electrical synchrony as biventricular pacing due to fusion. (4) Anterior LV pacing was less effective than
Acknowledgments
We thank Paul Kohanski, Leslie Ciancibello, Sheila Shaffer, and Elena DuPont for assistance in pacing and CT data acquisition and transfer.
References (26)
- et al.
Noninvasive electrocardiogram imaging of substrate and intramural ventricular tachycardia in infarcted hearts
J Am Coll Cardiol
(2001) - et al.
Noninvasive electrocardiographic imaging (ECGI)comparison to intraoperative mapping in patients
Heart Rhythm
(2005) - et al.
Electrocardiographic imaging (ECGI), a novel diagnostic modality used for mapping of focal left ventricular tachycardia in a young athlete
Heart Rhythm
(2005) - et al.
Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing
J Am Coll Cardiol
(2002) - et al.
Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing
J Am Coll Cardiol
(2004) - et al.
How many people with heart failure are appropriate for biventricular resynchronization?
Eur Heart J
(2000) - et al.
The effect of cardiac resynchronization on morbidity and mortality in heart failure
N Engl J Med
(2005) - et al.
Cardiac resynchronization in chronic heart failure
N Engl J Med
(2002) - et al.
Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure
Circulation
(1999) - et al.
Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay
Circulation
(2000)
Noninvasive electrocardiographic imagingreconstruction of epicardial potentials, electrograms, and isochrones and localization of single and multiple electrocardiac events
Circulation
Noninvasive ECG imaging of electrophysiologically abnormal substrates in infarcted heartsa model study
Circulation
Imaging dispersion of myocardial repolarization, Icomparison of body-surface and epicardial measures
Circulation
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The study was supported by Merit Award R37-HL-33343 and Grant R01-HL-49054 from the National Heart, Lung, and Blood Institute of the National Institutes of Health to Dr. Rudy. Dr. Rudy is the Fred Saigh Distinguished Professor at Washington University in St. Louis. Drs. Jia and Ramanathan are employees and stockholders of Cardioinsight, Inc., a company that plans to commercialize electrocardiographic imaging as a clinical tool. Dr. Rudy is a coinventor of the ECGI technology.